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2,200 | 29,552,749 | AUTHORS ' CONCLUSIONS This review has found that the use of valbenazine or extract of Ginkgo biloba may be effective in relieving the symptoms of tardive dyskinesia . | BACKGROUND Antipsychotic ( neuroleptic ) medication is used extensively to treat people with chronic mental illnesses .
Its use , however , is associated with adverse effects , including movement disorders such as tardive dyskinesia ( TD ) - a problem often seen as repetitive involuntary movements around the mouth and face .
This review , one in a series examining the treatment of TD , covers miscellaneous treatments not covered elsewhere .
OBJECTIVES To determine whether drugs , hormone- , dietary- , or herb-supplements not covered in other Cochrane review s on TD treatments , surgical interventions , electroconvulsive therapy , and mind-body therapies were effective and safe for people with antipsychotic-induced TD . | A single blind trial and a placebo controlled double blind trial of lithium were carried out in elderly patients with tardive dyskinesia . In the pilot study , neuroleptics were continued : in the controlled trial , neuroleptics were discontinued . The results of both studies were essentially negative . Thus , the suppression effect of neuroleptics is much more dramatic than anything seen in the two studies . Several reasons for this were discussed namely , the severity and chronicity of the symptoms Tardive dyskinesia ( TD ) is a serious , often disabling , movement disorder that is caused by medications that block dopamine receptors ( i.e. , neuroleptics , anti-emetics ) . There is currently no st and ard treatment approach for physicians confronted with such patients . This may be the result of notions that TD is disappearing because of the switch to second-generation antipsychotic agents and that it is largely reversible . In this article we demonstrate that second-generation antipsychotics do , indeed , cause TD and , in fact , the frequency is likely higher than expected because of growing off-label uses and a tripling of prescriptions written in the last 10 years . In addition , studies demonstrate that TD actually remits in only a minority of patients when these drugs are withdrawn . Furthermore , neuroleptic agents are often utilized to treat TD , despite prolonged exposure being a risk factor for irreversibility . The outcome of these trends is a growing population afflicted with TD . We review non-neuroleptic agents that have shown positive results in small , early-phase , blinded trials , including tetrabenazine , amantadine , levetiracetam , piracetam , clonazepam , propranolol , vitamin B6 , and Ginkgo biloba . Other options , such as botulinum toxin and deep brain stimulation , will also be discussed , and a suggested treatment algorithm is provided . While these agents are reasonable treatment options at this time there is a need , with a concerted effort between neurology and psychiatry , for full-scale drug development , including multicenter , r and omized , blinded trials to confirm the effectiveness of the agents that were positive in phase 2 trials and the development of newer ones Twenty patients with signs of tardive dyskinesia secondary to antipsychotic medication participated in a double blind , controlled , parallel group study comparing codergocrine mesylate 4.5 mg once daily with a placebo . After 6 weeks medication a reduction in dyskinetic scores occurred in both groups , but at the end of a further 6-week period the patients on active treatment maintained their improvement while those on placebo did not . This may be due to a slow onset of action and a hangover of activity associated with the drug 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 OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate Psychiatric in patients with tardive dyskinesia ( TD ) were treated with either lithium alone ( n = 9 ) or with a combination of lithium and lecithin ( n = 9 ) for 5 weeks in a double-blind , placebo-controlled experiment . A statistically significant but clinical ly unimportant improvement of TD occurred during both treatments . The addition of lecithin to lithium had no effect Despite the plethora of clinical drug trials in tardive dyskinesia , few consistent findings have emerged . One possible reason for this is that there have been no serious attempts to define the role of major neurotransmitter systems ( dopamine , norepinephrine , acetylcholine , serotonin , GABA ) in one specific population of tardive dyskinesia patients . This study reports a series of five controlled drug trials in a population of patients with persistent tardive dyskinesia ; each drug probed one of four neurotransmitter systems . The intra- and interpatient responses are analyzed and the implication s of the pharmacologic response profiles for the clinical management of tardive dyskinesia are discussed The effectiveness of a once-weekly i.m . injection of ceruletide ( 0.8 microgram/kg ) in suppressing the symptoms of neuroleptic-induced tardive dyskinesia ( TD ) was evaluated in a double-blind , placebo-controlled , matched-pairs study . Global evaluation of the severity of TD symptoms over the 8-week study period revealed a significant improvement with ceruletide as compared with placebo . Analysis of the therapeutic response to ceruletide over the course of treatment revealed a slow , but long-lasting improvement of TD symptoms . Side effects , which were mild and transient , consisted mainly of nausea and epigastric discomfort . The incidence of side effects did not differ between the ceruletide- and placebo-treated groups . Ceruletide appears to be a novel and practical treatment that can substantially alleviate the symptoms of dyskinesia The beneficial effect of estrogens on L -dopa-induced dyskinesias and on tardive dyskinesia has recently been reported . In this open pilot study , conjugated estrogens ( CE ) were BACKGROUND Antipsychotics remain the mainstay of drug intervention in the management of schizophrenia . However , long-term treatment with antipsychotics is associated with a variety of movement disorders , the most disabling of which is tardive dyskinesia ( TD ) , which occurs in up to 50 % of patients hospitalized with chronic schizophrenia . The pathophysiology of TD is still unclear and no definite treatment exists . Both dopamine receptor supersensitivity and oxidative stress-induced neurotoxicity in the nigrostriatal system are apparently implicated . The pineal hormone melatonin is a potent antioxidant and attenuates dopaminergic activity in the striatum and dopamine release from the hypothalamus . Thus , it may have a beneficial effect for both the treatment and prevention of TD . METHODS Using a double-blind , placebo-controlled , crossover study , we evaluated the efficacy of 10 mg/d of melatonin for 6 weeks in 22 patients with schizophrenia and TD . The primary outcome measure was the change from baseline in Abnormal Involuntary Movement Scale ( AIMS ) score . RESULTS The decrease ( mean + /- SD ) in AIMS score was 2.45 + /- 1.92 for the melatonin and 0.77 + /- 1.11 for the placebo treatment groups ( P<.001 ) . No adverse events or side effects were noted . CONCLUSION This is the first clinical evidence for efficacy of melatonin in the treatment of TD OBJECTIVE Worldwide , conventional antipsychotic medication continues to be used extensively , and tardive dyskinesia ( TD ) remains a serious complication . The primary objective of the present study was to compare the efficacy of EPA versus placebo in reducing symptoms of TD . METHOD This was a 12-week , double-blinded , r and omized study of ethyl-EPA 2g/day versus placebo as supplemental medication , in patients with schizophrenia or schizoaffective disorder , with established TD . RESULTS Eighty-four subjects were r and omized , of whom 77 were included in the analysis . Both the EPA and placebo groups displayed significant baseline to endpoint improvements in Extrapyramidal Symptom Rating Scale dyskinesia scores , but there were no significant between-group differences ( p=0.4 ) . Response rates ( > or=30 % improvement in TD symptoms ) also did not differ significantly between EPA-treated subjects ( 45 % ) and placebo-treated subjects ( 32 % ) ( p=0.6 ) . However , a post-hoc linear mixed model repeated measures analysis of variance indicated an effect for treatment group and duration of TD . The EPA-treated patients had significantly greater mean reductions in dyskinesia scores initially , although this was not sustained beyond 6 weeks . CONCLUSIONS This trial failed to demonstrate an anti-dyskinetic effect for ethyl-EPA 2g/day on the primary efficacy measure . However , a modest and transient benefit is suggested in patients with more recent onset of TD . The lack of clear-cut efficacy could be explained on the basis of the dose of EPA being too low , the study being underpowered , TD being too chronic in the majority of cases , differences in dietary fatty acid intake , or that EPA lacks an anti-dyskinetic action Eight psychiatric patients with tardive dyskinesia ( TD ) were treated with single doses of the synthetic met-enkephalin analogue FK 33 - 824 ( 1 , 2 , and 3 mg IM ) morphine ( 10 mg SC ) and naloxone , an opiate receptor antagonist ( 0.8 mg IM ) . The drug effects were assessed by blind evaluation of r and omly sequenced videotapes made before and during treatment . FK 33 - 824 ( 1,2 , and 3 mg IM ) slightly reduced TD ( P<0.05 ) and increased preexisting bradykinesia . The effect on TD , however , was pronounced only in patients concurrently treated with neuroleptics in relatively high doses . Morphine had a similar although weaker antihyperkinetic effect , whereas naloxone had no effect . Side effects of FK 33 - 824 included dizziness , heaviness in the extremities , slurred speech , and dryness of mouth . Morphine caused drowsiness , dizziness , ataxia , and nausea , and naloxone had no side effects . The results do not point to a primary role of enkephalin in the pathophysiology of TD , but enkephalin may interact with dopamine functions and potentiate some of the effects of neuroleptic drugs The unique role of ganglioside GM1 in neuronal plasticity led two centers , New York University and McLean Hospital , to study the effect of GM1 or placebo in patients with tardive dyskinesia . Results from the NYU cohort have already been published . We now present data from the entire cohort , allowing us to evaluate the effects of GM1 in the elderly compared to young adults . Subjects with tardive dyskinesia were r and omly assigned to single-blind placebo injections for 1 week , followed by 1 month of double-blind intramuscular placebo or GM1100 mg . The final sample included 29 patients : 12 younger than 55 years of age and 17 older . There was no GM1-versus-placebo difference observed in either-age group , or in the total group . However , whether on placebo or GM1 , repeated measures analysis of variance ( RANOVA ) found a significant difference in response between Abnormal Involuntary Movement Scale scores , taken baseline and week 4 , in the elderly compared to young adults . Scores for the young adults show initial improvement then deterioration back to baseline , and those for the elderly show continuing improvement during the 4-week trial . The importance of the placebo effect in the elderly and its meaning for studies of GM1 in tardive dyskinesia are discussed OBJECTIVE The study investigated the efficacy and tolerability of ethyl-eicosapentaenoic acid ( E-EPA ) as add-on treatment in chronic , severe schizophrenia . METHOD A r and omized , parallel-group , double-blind , placebo-controlled , fixed-dose , add-on study was conducted over 12 weeks . Forty patients with persistent symptoms after at least 6 months of stable antipsychotic treatment received E-EPA or placebo , in addition to their existing treatment . RESULTS At 12 weeks , the E-EPA group had significantly greater reduction of Positive and Negative Syndrome Scale total scores and of dyskinesia scores than the placebo group . CONCLUSIONS EPA may be an effective and well-tolerated add-on treatment in schizophrenia 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 BACKGROUND Piracetam is a potent antioxidant , a cerebral neuroprotector , a neuronal metabolic enhancer , and a brain integrative agent . More than 20 years ago , an intravenous preparation of piracetam demonstrated an improvement in the symptoms of tardive dyskinesia . The aim of our study was to reexamine the efficacy of piracetam in the treatment of tardive dyskinesia using an oral preparation . METHOD The study was conducted at the Be'er Sheva Mental Health Center from May 2003 to December 2004 and involved a 9-week , double-blind , crossover , placebo-controlled trial assessing 40 DSM-IV schizophrenic and schizo-affective patients with DSM-IV-TR tardive dyskinesia . All study subjects received their usual antipsychotic treatment . Initially , subjects were r and omly assigned to receive 4 weeks of treatment with either piracetam ( 4800 mg/day ) or placebo . Thereafter , following a washout period of 1 week , they entered the crossover phase of the study for a further 4 weeks . The change in score of the Extrapyramidal Symptom Rating Scale from baseline to the study endpoint was the primary outcome measure . RESULTS The mean decrease in score from baseline to endpoint in the clinical global impression subscale in patients treated with piracetam was 1.1 points compared to 0.1 points in the placebo group ( p = .004 ) . The mean decrease in the tardive parkinsonism subscale was 8.7 points in patients treated with piracetam and 0.6 points in those on placebo ( p = .001 ) . The mean decrease in the tardive dyskinesia subscale was 3.0 points in the piracetam group in contrast to deterioration of condition in the placebo group by -0.2 points ( p = .003 ) . CONCLUSION Piracetam appears to be effective in reducing symptoms of tardive dyskinesia . The specific mechanism by which piracetam may attenuate symptoms of tardive dyskinesia needs to be further evaluated . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00190008 Thirty in patients with evidence of tardive dyskinesia secondary to antipsychotic medications participated in this double-blind , controlled , r and omized study comparing reserpine , α-methyldopa and placebo . Reserpine at doses of 0.75–1.5 mg daily , or α-methyldopa at doses of 750–1,500 mg daily , produced a statistically significant improvement in tardive dyskinesia symptomatology compared to the results obtained with placebo Huntington 's Disease ( HD ) is a serious dominantly inherited neurodegenerative disorder for which there are no current treatments . Open label and animal studies have suggested that highly unsaturated fatty acids ( HUFAs ) may be beneficial . Seventeen patients with HD were entered into a r and omised , placebo-controlled , double blind trial of HUFA therapy . Patients were assessed on the Rockl and -Simpson Dyskinesia Rating Scale ( RSDRS ) and the Unified Huntington 's Disease Rating Scale ( UHDRS ) . On the RSDRS and the UHDRs motor scale patients on HUFA treatment improved while those on placebo deteriorated , with a significant difference between the two groups on the RSDRS . A similar trend was noted on the UHDRS functional performance scales . Little change was seen on the neuropsychology scales . There were no treatment-related adverse events . This is the first time that a significant improvement has been noted in a r and omised trial in HD . The results are consistent with open label observations ; a second placebo-controlled study in end-stage patients , and a study in a transgenic mouse model of HD ABSTRACT Background Tardive dyskinesia is a persistent movement disorder induced by chronic neuroleptic exposure . NBI‐98854 is a novel , highly selective , vesicular monoamine transporter 2 inhibitor . We present results of a r and omized , 6‐week , double‐blind , placebo‐controlled , dose‐titration study evaluating the safety , tolerability , and efficacy of NBI‐98854 for the treatment of tardive dyskinesia . Methods Male and female adult subjects with moderate or severe tardive dyskinesia were included . NBI‐98854 or placebo was given once per day starting at 25 mg and then escalated by 25 mg to a maximum of 75 mg based on dyskinesia and tolerability assessment . The primary efficacy endpoint was the change in Abnormal Involuntary Movement Scale from baseline at week 6 scored by blinded , central video raters . The secondary endpoint was the Clinical Global Impression of Change — Tardive Dyskinesia score assessed by the blinded investigator . Results Two hundred five potential subjects were screened , and 102 were r and omized ; 76 % of NBI‐98854 subjects and 80 % of placebo subjects reached the maximum allowed dose . Abnormal Involuntary Movement Scale scores for NBI‐98854 compared with placebo were significantly reduced ( p = 0.0005 ) . Active drug was also superior on the Clinical Global Impression of Change — Tardive Dyskinesia ( p < 0.0001 ) . Treatment‐emergent adverse event rates were 49 % in the NBI‐98854 and 33 % in the placebo subjects . The most common adverse events ( active vs. placebo ) were fatigue and headache ( 9.8 % vs. 4.1 % ) and constipation and urinary tract infection ( 3.9 % vs. 6.1 % ) . No clinical ly relevant changes in safety assessment s were noted . Conclusion NBI‐98854 significantly improved tardive dyskinesia and was well tolerated in patients . These results support the phase 3 clinical trials of NBI‐98854 now underway . © 2015 The Authors . Movement Disorders published by Wiley Periodicals , Inc. on behalf of International Parkinson and Movement Disorder Society Estrogen have been reported in animal studies to both enhance and block central dopaminergic activity and in one clinical report to improve tardive dyskinesia . In the present study estrogen ( Premarin , 2.5 mg per day ) administration caused varying degrees of improvement in less than one-third of 21 patients with chorea due to Huntington 's disease and tradive dyskinesia and had no effect in eight patients with dystonia . Estrogens appear to have an antidopaminergic effect in humans but poses only limited efficacy in the treatment of dyskinetic disorders Despite the proven efficacy of acute and maintenance pharmacotherapy in schizophrenia , practical methods for identifying patients who require continuous treatment to prevent relapse have not been established . We hypothesized that a pathologic overactivity of mesolimbic and mesocortical dopamine neural systems , that mediates positive psychotic symptoms in the acute phase of the illness , persists in some out patients who are vulnerable to relapse despite appearing clinical ly stable . To test and determine if putative measures of central nervous system dopamine activity predict outcome , 41 stable out patients receiving neuroleptic maintenance treatment underwent provocative tests with methylpheni date in a r and omized double-blind placebo controlled design in which behavioral , neuromotor , biochemical , and cardiovascular responses were measured . Patients were then withdrawn from medication and monitored for 52 weeks , or until relapse . The results indicate that psychotic symptoms and their activation by methylpheni date , and the presence of tardive dyskinesia are associated with each other and with a higher risk of relapse . These findings partially support our hypothesis and offer potentially useful measures for the identification of c and i date s for reduced dose neuroleptic maintenance treatment strategies in schizophrenia Tardive dyskinesia ( TD ) is thought to result from nigrostriatal dopaminergic supersensitivity secondary to prolonged neuroleptic exposure . Pre clinical studies have demonstrated that the opiate antagonist naloxone can acutely reverse a haloperidol-induced hyperdopaminergic state . In a trial of high-dose naloxone , 20 patients with TD received i.v . naloxone ( 20 mg , 40 mg , and placebo ) under double-blind conditions . At baseline and at regular postdrug intervals , patients were evaluated using a battery of motor , clinical , and neuropsychological measures to study effects on neurological , behavioral , and cognitive functions . There was a significant improvement in involuntary movements at 30 min postnaloxone , together with improvement in clinical ratings at that time point , as well as some cognitive changes . The implication s of these findings for the putative functional relationship between dopaminergic and enkephalinergic systems in the nigrostriatal area are discussed Tardive Dyskinesia ( TD ) is a movement disorder associated with the clinical administration of antipsychotics . It is believed that TD is due , among other factors , to an increase in the oxidative damage produced by free radicals . Antioxidants , like vitamin E , have been used in the treatment of TD but there is no evidence of their effectiveness . Melatonin ( MEL ) is 6 to 10 times more effective , as an antioxidant , than vitamin E and it has been used with an apparent higher effectiveness in the treatment of TD , although the results have not been conclusive . A r and omized , double blind , placebo controlled design was used to determine the effectiveness of MEL ( 20 mg/day ) during 12 weeks in 7 patients with TD . Six patients with TD were treated with placebo . The Abnormal Involuntary Movement Scale ( AIMS ) was chosen to assess the severity of TD initially and after 4 , 8 and 12 weeks . The psychiatric evaluation was done following the Brief Psychiatric Rating Scale . In two patients treated with MEL a significant improvement ( more than 60 % ) of the values of AIMS was detected . In the remainder five , as well as in the patients treated with placebo , no difference was observed during the 12 weeks . When compared the AIMS score in all the MEL-treated patients with the values in the placebo-treated patients , no significant differences were detected during the 12 weeks of the study . However , the significant clinical improvement observed in two patients must be considered before reaching a final conclusion on the usefulness of MEL in TD Pre clinical and clinical observations suggest that enhancement of prostagl and in activity inhibits catecholamine release and may have antidyskinetic effects . A double-blind therapeutic trial with prostagl and in precursor essential fatty acids was conducted in 16 patients with tardive dyskinesia . No beneficial effects were seen The subjects were 13 psychiatric in patients with tardive dyskinesia . Each subject participated in two sessions . Either naloxone ( 10 mg ) or placebo was administered intravenously during each session . In a subset of subjects ( n = 7 ) , blood sample s for beta-endorphin were drawn before and at 30 and 60 minutes after the injection . The Abnormal Involuntary Movement Scale was administered before and at 10 , 20 , 40 , 60 , 120 , and 360 minutes after the injection . Double-blind procedures were maintained throughout the experiment . Neither naloxone nor placebo had any appreciable effect on the involuntary movements . Naloxone elicited a significant increase in the plasma beta-endorphin Tardive dyskinesia ( TD ) induced by antipsychotic drugs represents a great concern for patients and psychiatrists . Considering its pathophysiological mechanisms , there exists a convergence towards the development of postsynaptic dopaminergic hypersensitivity as a possible cause of TD . Hypersensitivity following receptor blockade is the consequence of an increased number of receptors and such a synthesis is energy-dependent . In the brain , under normal conditions , energy is almost exclusively provided by glucose utilization . We thus hypothesized that , if glucose availability were reduced , the metabolically hyperactive structures should represent the best functional target of a reduction in fuel availability . Twenty chronic schizophrenic out patients ( 13 males , 7 females ) , aged 20 - 67 ( mean : 38.3 ) , accepted to participate in this double-blind , placebo-controlled study . They were r and omly assigned to either the insulin treatment group ( 10 patients ) or to the insulin-placebo group ( 10 patients ) . They received a subcutaneous injection of 10 units of st and ard insulin or placebo at 10 a.m. From day 1 to day 15 , injections were performed daily and , thereafter , every other week for 5 weeks totalizing 20 injections in 90 days . At day 7 , the insulin treatment group showed a sharp decrease in the intensity of TD symptoms which persisted throughout the duration of the study . By contrast , no change in TD symptomatology was observed in the insulin-placebo-treated group . Although a direct effect on DA neurones , or at least the participation of such an effect , can not be excluded , our data favor a role of decreased glucose availability in reversing receptor hypersensitivity Despite the proven efficacy of neuroleptic drugs in the acute and maintenance pharmacotherapy of schizophrenia , practical methods for identifying patients who require neuroleptic treatment to prevent relapse are lacking . This study evaluated the use of a methylpheni date challenge test to predict the outcome in 34 stable out patients with schizophrenia receiving neuroleptic treatment . Patients received two infusions , one of methylpheni date and one of placebo , in r and omized order one week apart while receiving neuroleptic treatment and again three weeks after drug withdrawal . Behavioral , cardiovascular , and neurologic responses were evaluated before and after infusion under double-blind conditions . Patients were then followed up without medication for 52 weeks or until symptom recurrence . The results indicate that specific measures , including behavioral response to methylpheni date , presence of tardive dyskinesia , and , under specific pharmacologic conditions , tardive dyskinesia , blink-rate , and pulse-rate responses to methylpheni date , are associated with time and propensity to relapse following neuroleptic withdrawal . These measures may be potentially useful in the identification of c and i date s for neuroleptic withdrawal and /or dosage-reduction treatment strategies BACKGROUND Tardive dyskinesia is a severe and disabling side effect of conventional antipsychotic treatment , with incidence rates reaching a high of 50 % in chronically institutionalized population s. On the basis of recent studies showing some benefit of antioxidants , we evaluated the effect of melatonin , the most potent naturally occurring antioxidant , on tardive dyskinesia in patients with chronic schizophrenia . METHOD Nineteen patients ( 8 men , 11 women ) , aged a mean + /- SD 74.0+/-9.5 years with chronic DSM-IV schizophrenia of 31.3+/-7.0 years ' duration , were r and omly assigned in a double-blind , placebo-controlled , crossover trial to receive slow-release melatonin , 2 mg/day , or placebo for 4 weeks . After a 2-week washout period , the patients were switched to the other treatment arm for an additional 4 weeks . The Abnormal Involuntary Movement Scale ( AIMS ) was administered at baseline , 4 weeks , 6 weeks , and 10 weeks . Regular administration of antipsychotic and other medications was kept unchanged throughout the study . RESULTS Mean AIMS scores did not change significantly from baseline in either treatment arm . All patients completed the study , and there were no side effects or adverse events . CONCLUSION Supraphysiologic doses of melatonin do not positively affect tardive dyskinesia . Considering that melatonin is a safe drug , further studies are needed of higher doses and in patients with shorter disease duration before its use in the treatment of tardive dyskinesia is ruled out The goal of this study was to determine whether selegiline ( L-deprenyl ) , a selective monoamine oxidase B inhibitor and antioxidant , would improve neuroleptic-induced tardive dyskinesia ( TD ) . Thirty-three patients with TD were r and omly assigned to selegiline 10 mg/day or placebo for 6 weeks and were assessed at baseline and at weeks 1 , 2 , 4 , and 6 for TD , parkinsonism , akathisia , depression , and positive and negative symptoms . Examinations for TD were videotaped and scored by a rater unaware of the temporal sequence of examination . Twenty-eight subjects completed at least 1 week of treatment ; all five dropouts were receiving selegiline . When baseline score and gender were controlled , the group receiving selegiline displayed significantly less improvement of TD compared with the placebo group . The two treatment groups did not differ in any other outcome measure . Selegiline was less effective than placebo in reducing symptoms of TD over a 6-week trial . This may be the result of the dopamine agonist effects associated with selegiline OBJECTIVE The goal of this study was to evaluate the efficacy and safety of levetiracetam versus placebo for tardive dyskinesia ( TD ) . METHOD This double-blind , placebo-controlled , r and omized study was conducted at the Connecticut Mental Health Center between September 2004 and April 2006 . Antipsychotic-treated patients meeting Glazer-Morgenstern criteria for TD were assigned at r and om to receive levetiracetam 500 mg/day to 3000 mg/day or placebo for 12 weeks . After completion of 12 weeks , patients were permitted to receive open-label levetiracetam for a further 12 weeks . The principal efficacy outcome measure was improvement in the Abnormal Involuntary Movement Scale ( AIMS ) total score . Safety was assessed with an adverse event scale , psychiatric symptom rating scales , weight , and hematologic tests . RESULTS A total of 50 patients were r and omly assigned to treatment . AIMS total scores were moderate in severity at baseline . Mixed regression models revealed that AIMS total scores declined 43.5 % from baseline in the levetiracetam group compared to 18.7 % for placebo ( p = .022 ) . Patients continuing levetiracetam in the open-label phase continued to improve , and patients crossed over to open-label levetiracetam improved to a similar degree as those initially assigned . Levetiracetam was well tolerated . CONCLUSION Levetiracetam appeared effective for TD in this study . The mechanisms of its therapeutic effect are unclear but may involve reducing neuronal hypersynchrony in basal ganglia . Future studies should attempt to replicate the current results . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00291213 OBJECTIVE Tardive dyskinesia is a persistent movement disorder induced by dopamine receptor blockers , including antipsychotics . Valbenazine ( NBI-98854 ) is a novel , highly selective vesicular monoamine transporter 2 inhibitor that demonstrated favorable efficacy and tolerability in the treatment of tardive dyskinesia in phase 2 studies . This phase 3 study further evaluated the efficacy , safety , and tolerability of valbenazine as a treatment for tardive dyskinesia . METHOD This 6-week , r and omized , double-blind , placebo-controlled trial included patients with schizophrenia , schizoaffective disorder , or a mood disorder who had moderate or severe tardive dyskinesia . Participants were r and omly assigned in a 1:1:1 ratio to once-daily placebo , valbenazine at 40 mg/day , or valbenazine at 80 mg/day . The primary efficacy endpoint was change from baseline to week 6 in the 80 mg/day group compared with the placebo group on the Abnormal Involuntary Movement Scale ( AIMS ) dyskinesia score ( items 1 - 7 ) , as assessed by blinded central AIMS video raters . Safety assessment s included adverse event monitoring , laboratory tests , ECG , and psychiatric measures . RESULTS The intent-to-treat population included 225 participants , of whom 205 completed the study . Approximately 65 % of participants had schizophrenia or schizoaffective disorder , and 85.5 % were receiving concomitant antipsychotics . Least squares mean change from baseline to week 6 in AIMS dyskinesia score was -3.2 for the 80 mg/day group , compared with -0.1 for the placebo group , a significant difference . AIMS dyskinesia score was also reduced in the 40 mg/day group ( -1.9 compared with -0.1 ) . The incidence of adverse events was consistent with previous studies . CONCLUSIONS Once-daily valbenazine significantly improved tardive dyskinesia in participants with underlying schizophrenia , schizoaffective disorder , or mood disorder . Valbenazine was generally well tolerated , and psychiatric status remained stable . Longer trials are necessary to underst and the long-term effects of valbenazine in patients with tardive dyskinesia Despite continued research , the influences that promote or exacerbate tardive dyskinesia ( TD ) symptoms remain incompletely understood . Recent findings ( Gardos et al. 1992 ; Richardson et al. 1989 ) suggest that ingestion of the dietary constituent , phenylalanine , might exacerbate TD symptoms , but a double-blind , placebo-controlled challenge had not previously been conducted in schizophrenic patients . On two different mornings , in counterbalanced order , 18 male schizophrenic patients with TD were challenged with either 100 mg/kg phenylalanine or placebo . Effects on abnormal involuntary movements , recall memory , and plasma phenylalanine were measured 90 minutes post-challenge . The results supported the hypothesis in that involuntary movements increased to a statistically and clinical ly meaningful degree after the phenylalanine challenge , but not after placebo . No effects on memory were detected . Significant order effects characterized the plasma findings but not the behavioral data . Results indicate that a dietary constituent , the amino acid phenylalanine , can potentially exacerbate tardive dyskinesia symptoms in schizophrenic patients . The influence of phenylalanine and other ingested substances on clinical symptomatology warrants further investigation BACKGROUND This paper evaluates the effects on knowledge and clinical stability of an educational intervention about tardive dyskinesia . METHOD Fifty-six patients receiving antipsychotic maintenance completed a question naire assessing their knowledge about tardive dyskinesia . After r and om allocation to either an educational intervention or a control group , their knowledge was reassessed at six months . RESULTS Ninety-five per cent of patients completed the study . The study patients gained significantly more knowledge than the controls , who made modest gains . There were no significant differences in clinical outcome between the groups . CONCLUSION Patients can learn about serious toxic effects of antipsychotic treatment with a low risk of non-compliance . Discussion about tardive dyskinesia is necessary in the process of obtaining informed consent to treatment OBJECTIVE The efficacy of the branched-chain amino acids in the treatment of tardive dyskinesia in men with psychiatric disorders was tested . METHOD Public-sector psychiatric patients with long histories of antipsychotic treatment and presumably long-st and ing tardive dyskinesia were r and omly assigned to receive branched-chain amino acids or placebo . Treatment frequency was three times a day , 7 days a week for 3 weeks . The efficacy measure was a frequency count of videotaped tardive dyskinesia movements . RESULTS A robust and highly significant difference was observed between patients who received high-dose branched-chain amino acids ( 222 mg/kg of body weight t.i.d . ) ( N=18 ) and those who received placebo ( N=18 ) in the percent change in tardive dyskinesia symptoms from baseline to the end of the 3-week trial . Significant and marked differences were seen between the two groups at the > /=30 % and > /=60 % levels of decrease in tardive dyskinesia symptoms . No clinical ly significant differences were seen between the pre- and posttrial results of physical examinations and laboratory screening tests . Minimal gastrointestinal symptoms occurred during the trial . The reduction in tardive dyskinesia symptoms in the amino acids group was not related to changes in antipsychotic and glucose plasma levels . A mechanism of response related to decreased amine neurotransmitter synthesis was suggested by the significant positive correlations observed between decreases in tardive dyskinesia symptoms and decreases in aromatic amino acid plasma concentrations over the course of the trial . CONCLUSIONS Branched-chain amino acids constitute a novel , safe treatment for tardive dyskinesia , with a strong potential for providing significant improvement in the diseased physiognomy of the afflicted person Methylpheni date , an amphetamine-like central nervous system ( CNS ) stimulant used successfully in reversing acute neuroleptic-induced neurological symptoms , was given in a placebo-controlled study to 17 patients with tardive dyskinesia . On global ratings three subjects were improved , six showed an increase in symptoms , and eight showed no changes . The authors conclude that methylpheni date is not effective in tardive dyskinesia and that the results of this study are in keeping with present knowledge about CNS pharmacology Objective : This paper evaluates the effects of an educational intervention about tardive dyskinesia on knowledge and clinical stability at long-term follow up . Method : Fifty-six patients receiving antipsychotic maintenance completed a question naire assessing their knowledge about tardive dyskinesia . After r and om allocation to either educational intervention or control group , their knowledge , clinical stability and rates of tardive dyskinesia were reassessed after four years . Results : Seventy per cent of patients completed the study . The patients in the educational group retained significantly more knowledge at follow up than at baseline but this knowledge was not significantly greater than that of the control group . There were no significant differences in the clinical outcomes between the groups . Conclusion : Patients can retain a small but significant amount of information with a low risk of noncompliance . Discussion about tardive dyskinesia is necessary in the process of obtaining informed consent to treatment A double-blind r and omized clinical trial was conducted among 10 post-menopausal women with tardive dyskinesia ( TD ) to test the effect of estrogen replacement of the severity of abnormal movements and other outcome variables . After 3 weeks of treatment , the mean Abnormal Involuntary Movement Scale ( AIMS ) score decreased by 38 % in the estrogen group and by 9 % in the placebo group ; the difference between groups was marginally significant ( p less than 0.10 ) . However , the small sample size and the imbalance between groups in baseline AIMS scores do not allow us to rule out the confounding effects of other prognostic factors . There were no significant differences between treatment groups for parkinsonian and psychological symptoms at any visit or for changes in these variables between visits . The findings of this preliminary trial are consistent with the results of other human and animal investigations , and they support the need for future research to underst and the role of estrogens in the neuropathology and treatment of TD The efficacy of electromyographic feedback training in reducing the magnitude and frequency of the oral-lingual movements associated with tardive dyskinesia ( TD ) was investigated in a groups design . Twenty adult male in patients diagnosed as having TD using the Abnormal Involuntary Movements Scale ( AIMS ) were r and omly assigned to one of two treatment conditions . Following identification , all participants were initially reduced to the lowest effective dosage of neuroleptics , and then discontinued from anticholinergics . Following one month on this regimen , they were given a course of feedback training consisting of ten 14-minute sessions . Group one participants were provided with a tone contingent upon oral-lingual movements above a yoked threshold . Group two participants were given noncontingent feedback tones generated r and omly . Weekly AIMS were administered as well as an initial baseline during each session to determine current level of oral-lingual activity . An analysis of session effects indicated significantly more suppression of oral-lingual activity in the contingent group versus the noncontingent feedback group . Jaw and forehead activity also measured showed reductions of similar magnitudes for both groups Patients with tardive dyskinesia showed no significant difference in CSF HVA when compared with groups of schizophrenic or depressives . CSF cAMP in the tardive dyskinesia group was significantly lower when compared to schizophrenics but not depressives . These results do not support a dopamine-receptor supersensitivity hypothesis in permanent tardive dyskinesia 1 . The therapeutic efficacy of papaverine for tardive dyskinesia was tested in 23 psychogeriatric and 18 chronic schizophrenic patients . Papaverine was given in slow-release capsules at 150 mg BID for one week followed by 300 mg BID for five weeks . A single blind design was used with blind raters and a 6-week no drug control condition . 2 . Oro-facial dyskinesia was significantly reduced by papaverine in the psychogeriatric group during the first six weeks . Only a few patients showed at least 50 % improvement of dyskinesia scores . Overall the drug effects were modest . 3 . Other findings of interest were a ) EEG showed increased per cent time of alpha and reduced beta 1 . b ) Parkinsonian side effects tended to confirm dopamine antagonism by papaverine . c ) No tolerance was seen after six weeks . d ) Elderly female patients and those with oro-facial dyskinesia appeared to respond best to papaverine In a double-blind crossover placebo controlled trial the effectivity of piracetam in neuroleptic-induced extrapyramidal side effects was confirmed . 40 psychotic patients treated with neuroleptics in an average daily dose equal to 600 mg of chlorpromazine were included in this study . Akathisia , tremor , muscle rigidity and dyskinesia were evaluated on a 4-point scale . The patients were r and omly divided into two subgroups--40 g of piracetam or placebo from identic ampoules were given i.v . with a crossover readministration after 60 min . The intensity of the extrapyramidal side effects was evaluated at 30-min intervals during 2 h. Piracetam was proved to be significantly effective in both subgroups , the onset of its action being between 30 and 60 min after i.v . administration . Possible interpretations of the observed piracetam effectivity are considered . Further trials with piracetam in neurologic complications during neuroleptic treatment , tardive dyskinesia included , are suggested This study reports the results of a trial of essential fatty acid ( EFA ) supplementation in psychiatric patients ( predominantly schizophrenics ) with movement disorders . Evidence of EFA deficiency in these patients was observed . The antidyskinetic effect of EFA supplementation was marginally significant but not clinical ly important . However , active treatment produced highly significant improvements in total psychopathology scores and schizophrenia subscale scores , and a significant improvement in memory OBJECTIVE The objective of this study was to compare the 3-year course of schizophrenia between persons with tardive dyskinesia ( TD ) and persons without TD on multiple outcome measures . METHOD Data were drawn from a large , prospect i ve , naturalistic study of persons treated for schizophrenia-spectrum disorders ( DSM-IV criteria ) in the United States , conducted between July 1997 and September 2003 . Treatment outcomes were assessed at enrollment and at 12 , 24 , and 36 months postenrollment using measures of symptoms , functioning , productivity , activity , and quality of life . Participants who had TD at enrollment ( fulfilling Schooler-Kane criteria , N = 637 ) were compared with those who did not ( N = 1538 ) on clinical and functional measures at enrollment and across the 3 years of follow-up . Additional analyses examined those with persistent TD compared to those without persistent TD . RESULTS With adjustment for known correlates of TD , participants with TD compared to those without TD had significantly more severe psychopathology , were less likely to experience symptom remission , had more severe extrapyramidal side effects , and had lower levels of quality of life and functioning , lower productivity , and fewer activities ( all p < .001 ) across the 3-year follow-up . Findings were essentially unchanged when the subgroup of participants with persistent TD ( at enrollment and at 1 year ) was examined . CONCLUSION These results indicate that , in the long-term treatment of schizophrenia , persons with TD have a significantly more severe and more refractory course of illness than those without TD , suggesting poorer prognosis and the need for specialized interventions OBJECTIVE Free radicals may be involved in the pathogenesis of tardive dyskinesia ( TD ) . Extract of Ginkgo biloba ( EGb ) is a potent antioxidant possessing free radical-scavenging activities . The aim of the study was to evaluate the efficacy of EGb-761 , a st and ardized extract given in capsule form , in treating TD in schizophrenia patients . METHOD In patients with DSM-IV-diagnosed schizophrenia and TD ( n = 157 ) in a mainl and China Veterans Affairs psychiatric hospital were r and omly assigned to 12 weeks of treatment with either EGb-761 , 240 mg/d ( n = 78 ) or a placebo ( n = 79 ) in a double-blind manner . Primary outcome measures were ( 1 ) change from baseline in the Abnormal Involuntary Movement Scale ( AIMS ) score and ( 2 ) proportion of patients with a ≥ 30 % reduction in their AIMS total score at week 12 . Secondary outcome measures included the Positive and Negative Syndrome Scale ( PANSS ) and cognitive performance as measured by the Continuous Performance Test-37 Version and the 3-card Stroop task . Patients were recruited for the study between December 2006 and May 2007 . RESULTS Of the 157 patients who were r and omly assigned , 152 ( 96.8 % ) completed the study . EGb-761 treatment significantly decreased the AIMS total score in patients with TD compared to those who were given a placebo ( 2.13 ± 1.75 vs -0.10 ± 1.69 ; P < .0001 ) , with 40 ( 51.3 % ) and 4 ( 5.1 % ) patients achieving response in the EGb-761 and placebo treatment groups , respectively . There were no between-group differences in the PANSS total score or cognitive measures from baseline to week 12 . CONCLUSIONS EGb-761 appears to be an effective treatment for reducing the symptoms of TD in schizophrenia patients , and improvement may be mediated through the well-known antioxidant activity of this extract . TRIAL REGISTRATION clinical trials.gov identifier : NCT00672373 Augmentation of excitatory neuronal activity by enkephalins may be achieved by depression of firing of inhibitory γ-aminobutyric acid-ergic ( GABAergic ) neurons ( 1–3 ) . The latter findings and consideration of roles of GABAergic neurons in information processing in the central nervous system ( 4–7 ) led one of us ( E.R. ) to propose that the effects of low doses of naloxone be investigated in disorders in which there may be excessive disinhibition , among which may be tardive dyskinesia ( TD ) . We now report results obtained with two schizophrenic women with TD who were given naloxone in a short-term , double-blind study 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 15 hospitalized patients suffering from neuroleptic-induced tardive dyskinesias participated in a double-blind cross-over study of lithium sulphate and placebo . Each drug was given for 3 weeks . The results were evaluated by means of the video-tape technique . Lithium sulphate induced a slight , but significant reduction in the tardive dyskinesia . Lithium had , in addition , a suppressive effect on psychomotor agitation and aggression . The concentrations of homovanillic acid and 5-hydroxyindoleacetic acid were determined in the cerebro-spinal fluid from five patients . It is concluded that lithium can be used with advantage in the treatment of tardive dyskinesia with only moderate intensity , particularly when the movement disturbances are accompanied by psychomotor restlessness . Finally , the effect of lithium on the central aminergic transmitter substances is discussed in relation to the existing hypotheses on the pathophysiology of tardive dyskinesia Omega-3 fatty acids , particularly eicosapentaenoic acid ( EPA ) , are increasingly being used by psychiatric patients . Most studies have concentrated on efficacy aspects , while little is known about their safety and tolerability in psychiatric population s. This study aim ed to assess the effects of EPA treatment on body mass , glucose metabolism , lipid profiles , prolactin secretion , bleeding time , haematology and liver functions . Eighty-four subjects with schizophrenia were treated with either EPA 2 g/day or placebo in addition to their antipsychotic medication for 12 weeks , in a r and omized , controlled trial . Forty-seven entered a 40-week open-label extension phase of EPA 2 g/day . Seventy-four patients were included in the analysis . Six patients discontinued from the EPA group and 14 in the placebo group . Adverse event reporting was similar for the two groups . While there were no significant between-group differences , in the blinded phase the EPA group showed a significant increase in body mass index ( BMI ) and bleeding time . In the open-label extension , there was again a modest increase in BMI . Total cholesterol and HDL levels were significantly decreased . EPA 2 g/day is generally well tolerated . Clinicians should be aware of possible increases in bleeding time , as well as changes in weight and lipid metabolism Preliminary results on a small number of patients indicate that naloxone might have a beneficial effect in tardive dyskinesia ( TD ) ( Blum et al. 1983 , 1984 ; S and yk and Snider 1985 , 1986 ) . In order to examine this assumption , this study was performed in 13 patients suffering from chronic schizophrenia and long st and ing TD . The patients ( eight women and five men ) were aged 61 - 75 years . Their pertinent clinical data are shown in Table 1 . One week prior to naloxone administrat ion all other forms of medication except phenothiazines and butyrophenones were stopped . Naloxone was administered intravenously ( IV ) in a dosage of 0.8 mg . One day prior to or after naloxone administration , an equal volume of saline was administered in a similar fashion , in a double blind manner , so that patients served as their own controls . The intensity of dyskinetic movements was scored according to the Abnormal Involuntary Movement Scale ( AIMS ) . The dyskinetic movements were recorded before and at 5 , 10 , 20 and 60 rain after the IV injection . The changes in the intensity of dyskinetic movements after naloxone administrat ion are shown in Table 1 . In three patients , one man and two women , naloxone induced a dramatic improvement in dyskinetic movements . In two patients ( Nos 1 and 2 ) the movements were abolished . In another case ( patient No. 3 ) the intensity of the movements was decreased . The amelioration was observed immediately after naloxone administrat ion and diminished after 1 h. In the other ten patients no change was observed in dyskinetic movements . The change in intensity did not seem to be correlated to age or sex , but positive results were observed in three patients who developed TD less than 3 years prior to naloxone administration . No side effects of naloxone were observed . Saline administrat ion produced no changes in the intensity or frequency of the dyskinetic movements . The results obtained during the present study showed that naloxone treatment was effective only in those patients in whom the disease was of relatively short duration . It is possible that long st and ing TD is accompanied by Objective : Treatment of dyskinetic disorders , in general , and of tardive dyskinesia ( TD ) , in particular , is difficult . The opiate peptide enkephalin coexits with gamma aminobutyric acid in the projection neurons of striatum forming the " indirect " pathway . Several lines of pre clinical evidence implicate this enkephalin-comediated pathway in the pathophysiology and therapeutics of dyskinesia . However , previous studies , most using relatively low doses of opioid antagonists , showed mixed results . The goal of the current study was to test whether moderately high doses of naltrexone , alone or in combination with a subtherapeutic dose of a gamma aminobutyric acid agonist , improve TD . Methods : In 2 double-blind , placebo-controlled , r and omized , crossover trials , effects of naltrexone alone ( n = 9 ) and in combination with clonazepam ( n = 14 ) were tested on TD . In both trials , patients ' antipsychotic medication and dose remained unchanged through the trial . Naltrexone dose was increased over a period of 3 weeks to 200 mg/d and maintained at that dose for another week . In the second study , patients were first stabilized on low dose ( 0.25 to 0.5 mg ) of clonazepam for 4 weeks or longer . In addition to the TD scores , saccadic peak velocity and latency , as measures of vigilance , and antisaccade error rate were obtained during the fourth week of placebo and naltrexone in a subgroup of patients . Results : There were no significant effects of naltrexone alone on TD ( mean ± SD decrease in TD score = 0.1 ± 4.8 ) , psychosis scores , or eye movement measures . Low dose of clonazepam had no effect on TD . However , addition of naltrexone significantly improved TD ( mean , SD decrease in TD score 4.0 ± 3.6 ) . There was no clinical or laboratory evidence of increased sedation during treatment with naltrexone compared to placebo . There were no significant effects on the antisaccade error rate or psychosis scores . Conclusion : These findings suggest effectiveness of a strategy of combining a GABA(gamma aminobutyric acid)mimetic drug with an enkephalin antagonist to treat dyskinesia A double-blind crossover study on the effects of deanol and lithium carbonate was conducted on a sample of 29 chronic schizophrenic patients with tardive dyskinesia . In addition to his usual treatment with different neuroleptics , each patient received during an 8-week period either deanol , lithium carbonate or placebo . A 4-week wash-out period was inserted between each of the 8-week periods of experimental treatment of the tardive dyskinesia . The administration of either deanol , lithium carbonate or placebo added to the neuroleptic treatment did not produce a statistically significant improvement of tardive dyskinesia in our patient population as a whole . Favorable and unfavorable responses are discussed 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 ( enrollment , 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 |
2,201 | 28,749,101 | Lack of knowledge about CCa and BCa , and underst and ing of the role of screening were the key barriers to CCa and BCa screening in LMICs .
Conclusions : Improvements to CCa and BCa screening uptake in LMICs must be accompanied by educational interventions which aim to improve knowledge and underst and ing of CCa and BCa and screening to asymptomatic women . | Background : Cervical cancer ( CCa ) and breast cancer ( BCa ) are the two leading cancers in women worldwide .
Early detection and education to promote early diagnosis and screening of CCa and BCa greatly increases the chances for successful treatment and survival .
Screening uptake for CCa and BCa in low and middle - income countries ( LMICs ) is low , and is consequently failing to prevent these diseases .
We conducted a systematic review to identify the key barriers to CCa and BCa screening in women in LMICs . | Objective To determine cervical cancer screening coverage and the knowledge , attitudes and barriers toward screening tests among women in rural and urban areas of Tanzania , as well as explore how they view the acceptability of the HPV vaccine and potential barriers to vaccination . Setting A cross-sectional study using interview-administered question naires was conducted using multistage r and om sampling within urban and rural areas in Kilimanjaro Region , Tanzania . Participants Women aged 18–55 were asked to participate in the survey . The overall response rate was 97.5 % , with a final sample of 303 rural and 272 urban dwelling women . Primary and secondary outcome measures Descriptive and simple test statistics were used to compare across rural and urban strata . Multivariate logistic regression models were used to estimate ORs and 95 % CIs . Results Most women ( 82 % ) reported they had heard of cervical cancer , while self-reported cervical cancer screening among women was very low ( 6 % ) . In urban areas , factors associated with screening were : older age ( OR=4.14 , 95 % CI 1.86 to 9.24 for ages 40–49 , and OR=8.38 , 95 % CI 2.10 to 33.4 for > 50 years ) , having health insurance ( OR=4.15 , 95 % CI 1.52 to 11.4 ) , and having knowledge about cervical cancer ( OR=5.81 , 95 % CI 1.58 to 21.4 ) . In contrast , among women residing in rural areas , only condom use ( OR=6.44 , 95 % CI 1.12 to 37.1 ) was associated with screening . Women from both rural and urban areas had low vaccine-related knowledge ; however , most indicated they would be highly accepting if it were readily available ( 93 % ) . Conclusions The current proportion of women screened for cervical cancer is very low in Kilimanjaro Region , and our study has identified several modifiable factors that could be addressed to increase screening rates . Although best implemented concurrently , the availability of prophylactic vaccination for girls may provide an effective means of prevention if they are unable to access screening in the future AIMS The aims of this study were ( 1 ) to estimate what proportion of rural females had received cervical screening , ( 2 ) to assess knowledge , beliefs , attitudes , and demographics that influence cervical screening , and ( 3 ) to predict cervical screening accessibility based on demographic factors , knowledge , beliefs , and attitudes that influence cervical screening . METHODS The study sample consisted of r and omly selected , sexually active , rural females between 12 and 84 years of age . Five hundred fourteen females responded to an individually administered question naire . RESULTS Of the 514 participants , 91 % had never had cervical screening and 81 % had no previous knowledge of cervical screening tests ; 80 % of the group expressed positive beliefs about cervical screening tests after an educational intervention . Females who were financially independent were 6.61 % more likely to access cervical screening compared with those who were dependent on their husb and s. Females in mining villages were 4.47 % more likely to access cervical screening than those in traditional rural reserve villages . Females in resettlement villages were 20 % less likely to access cervical screening than those in traditional rural reserve villages . CONCLUSIONS Accessibility of screening services could be improved through planning and implementation of screening programs involving community leaders and culturally appropriate messages . The government should incorporate the human papillomavirus ( HPV ) vaccine in its immunization program for adolescents , and health education should be intensified to encourage women and their partners to comply with diagnostic and treatment regimens Background The Family Medical Program is a health care system in the Rio de Janeiro state . Women ’s health services offered by the Family Medical Program include preventive exams and screening , family planning , and prenatal follow-up . Although cervical cancer screening is offered , barriers to care still hinder the full success of the program , and we are attempting to identify these barriers . Methods We undertook a cross-sectional and prospect i ve study involving 351 women who were referred to the Family Medical Program between March 2009 and November 2010 . Demographic data were obtained through a structured household question naire . The dependent variable was defined as the non-realization of the Pap smear test following the protocol of the Health Ministry . Cervical sample s for screening were collected after clinical examination . Results Women who had undergone Pap smear testing at least once every 3 years comprised 282 of the participants ( 80.3 % ) . Most of the women had normal or inflammatory cytology ( 96.3 % ) . Illiteracy and the absence of symptomatic episodes of sexually transmitted disease were independent barriers to having cancer screening at regular intervals . Illiterate women were more likely to be older , not to be using any contraceptive method , and on average had more than two children , more than four pregnancies , and more than two abortions . Embarrassment was the greatest barrier to seeking professional care reported by all women , regardless of level of educational attainment . Other important barriers to seeking care and /or screening included time constraints , due to work or childcare . Conclusion This study indicates that the Family Medical Program effectively provides cervical cancer screening coverage for its eligible population , at the level m and ated by the WHO and the Brazilian Health Ministry . Fully 96.3 % of the women in our study had normal or benign inflammation on cytology . Underst and ing of barriers to care-seeking behavior that limit program adherence is one way to facilitate communication between providers and patients regarding the benefits of cancer screening Objectives . Community based breast cancer screening has decreased breast cancer mortality in women . This study examined the predictors of nonattendence for invitational breast cancer screening in relation to socioeconomic status in the city of Manisa , in western Turkey . Study Design . For the evaluation of the reasons for refusing to participate in the study , two districts were selected . 446 women aged between 50 and 69 years were selected from the program data base by systematic r and om sampling . Methods . The question naire consisted of sociodemographic variables and the adapted version of Champion 's Health Belief Model Scale . Univariete and multivariete logistic regression analysis were performed throughout the data analysis . Results . Being from an urban district and being from the western region were the risk factors for not participating in the screening program ( P = 0.014 , P = 0.023 ) . A statistical significance was found between mammography-benefit , mammography-barrier and program participation ( P = 0.044 , P = 0.006 ) . Although there were many more barriers for not participating in the screening program for the women of the slum district , the attendence rate of the slum district was higher than that of the urban district . Conclusions . Increased attendance may be achieved through enhancement of breast cancer awareness and by reducing some of the modifiable barriers Background To date , because of limited budgets and lower incidence of breast cancer , the majority of Asian countries do not have population -based screening programmes , but instead offer opportunistic screening . However , there have been few studies which have assessed the motivators for women attending such programmes and the appropriateness of the programmes in terms of targeting women at risk . Methods We conducted a prospect i ve cross-sectional study of 1,619 women aged 40 to 74 years attending a subsidized opportunistic screening mammogram from October 2011 to October 2013 at a private hospital in Malaysia . Breast cancer risk was estimated using the Gail Model and two-step cluster analysis was used to examine the motivators of attending screening . Results Although Malaysia comprises 54.5 % Malay , 24.5 % Chinese and 7.3 % Indian , the majority of women in the MyMammo Study were Chinese ( 70.1 % ) and 99.2 % had a < 2 % ten-year risk of breast cancer . The most commonly cited barriers were the perception of not being at risk and fear of painful mammography . We found that highly educated women , cited doctors , family and friends as their main motivators . Of those with only secondary school education , their main motivators were doctors . Conclusions Taken together , our results suggest the women attending opportunistic mammography screening in Asia are at low risk of breast cancer and this poses challenges to cost-effective and equitable strategies for cancer control . We propose that to improve uptake of screening mammography , awareness programmes should target both doctors and members of the public The purpose was to examine breast cancer screening behavior in Turkish women , the reasons for not doing screening and the relationship between health beliefs and levels of self-esteem , body perception , and hopelessness . This research was conducted as a descriptive , correlational study in an area covered by three neighborhood primary health care clinics in Bornova , Izmir . The data were collected between April and November 2006 from 382 women over 40 years of age who were selected using a stratified r and om sampling method and a descriptive information form , Champion 's Health Belief Model Scale ( CHBMS ) , the Rosenberg Self-Esteem Scale ( RSES ) , the Body Cathexis Scale ( BCS ) and the Beck Hopelessness Scale ( BHS ) . The breast cancer screening methods used by women participating in the research were , respectively , mammography ( 34 % ) , clinical breast examination ( 14.1 % ) , breast self-examination ( BSE ) ( 59.4 % ) . The reasons why women did not do breast cancer screening methods were determined to be : not having any symptoms , neglect , not sensing the need , and not knowing how BSE is done . In the examination of the women 's CHBMS subscale score means and RSES , BCS and BHS score mean a statistically significant relationships were determined between Benefits -BSE , Barriers-BSE , Confidence , Health motivation , Benefits -mammography and barriers-mammography subscale score means and RSES , BCS and BHS mean scores ( p<0.01 ) . It was found out that women with high level of self-esteem , high level of hope for the future and with a positive body perception have more positive health beliefs on breast cancer screening INTRODUCTION Cervical cancer is the third most common cancer among Malaysian women . However , the uptake of cervical cancer screening -- Pap smear -- by women in Malaysia has been low and remains a challenge . This study was conducted to assess the cervical screening practice s of rural women in Malaysia and to examine the factors associated with such practice s. METHODS A cross-sectional survey was conducted in five rural districts in Perak , Malaysia . 1,000 households were selected through multistage r and om sampling . Women aged 20 - 64 years were interviewed by trained enumerators using structured question naires . Binomial logistic regression was used to identify predictors of cervical screening through univariate and multivariate analyses . RESULTS Among the 959 respondents , only 48.9 % had undergone Pap smear at least once in the past three years . Women in the age group 40 - 49 years ( odds ratio 3.027 , 95 % confidence interval 1.546 - 5.925 ; p < 0.005 ) were found to be significantly more likely to attend cervical cancer screening as compared to those in the age group 20 - 29 years . Other significant predictors were being married with children , having knowledge of cervical cancer symptoms , receiving relevant information regarding cervical cancer from health personnel or campaigns , being engaged in family planning and receiving encouragement from husb and s. CONCLUSION Efforts to boost the uptake of Pap smear screening among the rural population should be targeted toward the predictors of positive uptake BACKGROUND Success of cervical screening initiatives depends on high participation of the target population , which in turn is determined by the women 's perceptions , health orientation and other socio-cultural issues . The present study identifies the immediate social and cultural barriers that prevent women to attend cervical screening facilities . METHODS Women non-compliant to a community-based cervical screening program were identified . From them 500 were r and omly selected for interview using a structured question naire that was design ed on the basis of feedbacks received from several focused group discussion s. Question naire listed 24 possible reasons for non-compliance . The women were asked to select the most pertinent reason(s ) for her non-attendance or to reveal if they had any reason other than the listed ones . RESULTS A total of 469 non-compliant women were interviewed . They had significantly lower literacy rate compared to the compliant women ( OR=2.25 ; 95 % CI : 1.23 - 4.13 ) . Nearly half of the interviewed women responded that they themselves opted to stay away from the program . Most common reasons cited for non-attendance in this group were reluctance to go for medical test in the absence of any symptoms and apprehension to have a test that detects cancer . Second major group of responders comprised of women who were willing , yet could not attend due to various hurdles . Most common hurdles were inability to leave household chores , pre-occupation with family problems and lack of approval from husb and s. CONCLUSIONS Modification of health behavior through education and social empowerment of women are essential for a population based cervical screening program to succeed in India BACKGROUND In India , breast cancer is the leading malignancy among women in a majority of the cancer registries . Therefore it is important to underst and screening practice s and its predictors , including in rural areas with high female literacy and good health indices . MATERIAL S AND METHODS A cross-sectional study with multistage sampling was conducted in Vypin Block , Ernakulam district , Kerala , India . Four Panchayats ( self administration units ) were r and omly chosen and a woman in every second household was invited to participate from the tenth ward of each . Thus a total of 809 women were interviewed . RESULTS The majority of the repondents ( 82.1 % ) were not aware of risk factors and about a third ( 37.9 % ) were not aware of symptoms of breast cancer . About half of the population studied ( 46.6 % ) had undergone screening . Age ( 35 - 50 years ) , being married , health professionals as source of information and working were significant predictors of screening . Logistic regression showed that older women ( 35 - 50 yrs ) were more likely to practice screening . Out of the never screened , about a third ( 35 % ) were desirous of doing it , but had not for various reasons and 53.5 % were not willing to screen . The reasons identified for not screening among those desirous of doing it were grouped into knowledge 66 ( 43.4 % ) , re sources 23 ( 15.1 % ) and psychosocial 32(21.1 % ) factors . Unmarried women were significantly more likely to express factors related to all the three domains . CONCLUSIONS This study showed that in spite of the absence of a population -based screening program , about half of the study population had undergone some type of screening . The older women ( 35 - 50 years ) in particular were significantly more likely to practice screening . At this critical juncture , a high quality breast cancer awareness and screening initiative can help to consoli date the gains and tackle knowledge , re source and psychosocial barriers |
2,202 | 25,558,390 | According to the results , there is no statistically significant difference in different doses of PZQ for treating S. japonicum | BACKGROUND Praziquantel , an antischistosomal compound , is used as first-line drug for chemotherapy of Schistosoma japonicum since 1984 .
In this article , we conducted a systematic review and mete- analysis to evaluate the efficacy and safety of different dosages of praziquantel ( PZQ ) for treatment of Schistosoma japonicum . | Praziquantel , a new antischistosomal compound , was tested for tolerance and efficacy against placebo in two double-blind clinical trials in Philippine patients infected with Schistosoma japonicum . The compound was given orally at a dose of 3 x 20 mg/kg at intervals of 4 hours to a total of 82 patients -some without advanced disease and some with hepatosplenic involvement . A total of 43 patients received placebo . In a single-blind trial , 42 patients were given a single oral dose of 50 mg/kg . Monitoring of vital organ functions included comprehensive laboratory tests and serial electrocardiograms . In 38 patients with hepatosplenic involvement due to advanced stages of infection , serial electroencephalograms were additionally recorded . No toxic effects were observed in any of these examinations . Undesirable side effects occurred in 53 % of the patients given 3 x 20 mg/kg and in 70 % after a dose of 1 x 50 mg/kg . They consisted mainly of abdominal discomfort , fever , sweating , and occasionally giddiness , but in general were transient and mild . At 6 months post-treatment , 60 of 75 patients treated with 3 x 20 mg/kg and 29 of 41 treated with 1 x 50 mg/kg were completely negative for eggs . At 12 months post-treatment , 25 of 33 and 14 of 26 patients in the two treatment groups were cured . Thus the divided dosage gave a superior therapeutic result . Praziquantel proved to be free of major toxicity , and was well tolerated , highly effective , and easy to administer . Confirmation of results in extended trials may soon permit large-scale treatment The first clinical trials of praziquantel against Schistosoma japonicum infections in Japan were planned to assess tolerance only . Three double-blind studies against placebo involving a total of 51 patients were conducted with dosages of praziquantel of 1 x 20 mg/kg body weight , 2 x 20 mg/kg , 3 x 20 mg/kg given on one day . The frequency of unwanted side effects was higher in the group of patients given praziquantel at a dose of 3 x 20 mg/kg than in all other drug- or placebo-treated patients . In general , the side effects , which included drowsiness , headache , lumbago , abdominal fullness , or epigastric discomfort , lasted for several hours but disappeared spontaneously . The results of laboratory tests showed no significant changes caused by treatment . The overall assessment showed excellent or good tolerance in all patients treated with praziquantel at the lower dose levels . In those given 3 x 20 mg/kg , tolerance was excellent in 1 of 12 patients , good in 9 , and fair in 2 , whereas the respective placebo-treated group showed excellent tolerance in 3 of 12 , good in 7 , and fair in 2 The combined effects of praziquantel and artesunate in the treatment of urinary schistosomiasis were assessed among 312 r and omly selected schoolchildren aged 4 - 20 years in Adim community , Nigeria . In the preliminary screening , infection was confirmed in 327 ( 38.5 % ) of the 850 subjects screened . Infected subjects who reported for treatment were then divided into six treatment groups of 52 subjects each ; 44 subjects in each group completed their treatment regimens and su bmi tted their urine for post-treatment assessment . Praziquantel and artesunate were administered orally at 40 mg/kg and 4 mg/kg body weight , respectively . Adverse effects due to drug reactions were assessed 72 h after medication and all perceived episodes of illness were treated . Morbidity indicators were assessed 56 days after the final dose of the drug regimens . All treatment regimens were well tolerated . The cure rates were 72.7 % in the praziquantel plus placebo-treated group and 70.5 % in the artesunate plus placebo group , while the artesunate plus praziquantel group had the highest cure rate ( 88.6 % ) . Haematuria and proteinuria were extensively reduced after treatment with the three drug regimens . This study confirmed that the treatment of urinary schistosomiasis with the combination of praziquantel and artesunate is safe and more effective than treatment with either drug alone |
2,203 | 23,441,167 | It was also shown that EGFR GCN is independent of other factors such as KRAS status .
Among the anti-EGFR-treated patients , increased EGFR GCN appears to be associated with improved survival outcomes .
The effect on survival appears to be related to patients receiving the line of treatment | BACKGROUND The epidermal growth factor receptor ( EGFR ) gene copy number ( GCN ) has been previously demonstrated to correlate with the clinical outcome of colorectal cancer ( CRC ) treated with anti-EGFR monoclonal antibodies ( mAbs ) , although it remains controversial .
We conducted a systematic review and meta- analysis to assess EGFR GCN as a potential biomarker of survival for patients with advanced CRC receiving treatment with anti-EGFR mAbs . | BACKGROUND St and ardized conditions to distinguish sub population s of colorectal cancer ( CRC ) patients more and less sensitive to cetuximab therapy remain undefined . MATERIAL S AND METHODS We retrospectively analyzed epidermal growth factor receptor ( EGFR ) copy number by fluorescence in situ hybridization ( FISH ) in paraffin-embedded tumor blocks from 85 chemorefractory CRC patients treated with cetuximab . Results were analyzed according to different score systems previously reported in colorectal and lung cancers . The primary end point of the study was identification of the EGFR FISH score that best associates with response rate ( RR ) . RESULTS Using receiver operating characteristic ( ROC ) analysis , the cut-off that best discriminated responders versus nonresponders to cetuximab was a mean of 2.92 EGFR gene copies per cell . This model showed sensitivity of 58.6 % [ 95 % confidence interval ( CI ) = 47.1 - 70.1 ) and specificity of 93.3 % ( 95 % CI = 80.6 - 100 ) . EGFR FISH-positive patients ( N = 43 , 50.6 % ) had significantly higher RR ( P = 0.0001 ) and significantly longer time to disease progression ( P = 0.02 ) than EGFR FISH negative ( N = 42 , 49.4 % ) . Other scoring systems result ed less accurate in discriminating patients with the highest likelihood of response to cetuximab therapy . CONCLUSIONS CRC patients with high EGFR gene copy number have an increased likelihood to respond to cetuximab therapy . Prospect i ve clinical trials with a careful st and ardization of assay conditions and pattern interpretation are urgently needed BACKGROUND The antiepidermal growth factor receptor ( antiEGFR ) monoclonal antibodies cetuximab and panitumumab have good clinical activity in about 10 % of patients with metastatic colorectal cancer that is resistant to chemotherapy . The molecular mechanisms underlying clinical response or resistance to these agents are unknown . METHODS Tumours from 31 patients with metastatic colorectal cancer who had either an objective response ( n=10 ) or stable disease or progressive disease ( n=21 ) after treatment with cetuximab or panitumumab were screened for genetic changes in EGFR or its immediate intracellular effectors . Specifically , we assessed the EGFR copy number and the mutation profile of the EGFR catalytic domain and of selected exons in KRAS , BRAF , and PIK3CA . RESULTS Eight of nine of patients with objective responses who were assessable by fluorescence in-situ hybridisation ( FISH ) had an increased EGFR copy number . By contrast , one of 21 non-responders assessable by FISH had an increased EGFR copy number ( p<0.0001 for responders vs non-responders , Fisher 's exact test ) . The mutation status of the EGFR catalytic domain and its immediate downstream effectors PIK3CA , KRAS , and BRAF did not correlate with disease response . In colorectal-cancer cell lines , the concentration of cetuximab that completely inhibited proliferation of cells with amplified EGFR copy number did not affect proliferation of cells with unamplified EGFR . INTERPRETATION We propose that the response to antiEGFR treatment has a genetic basis and suggest that patients might be selected for treatment on the basis of EGFR copy number BACKGROUND A large proportion of colorectal cancer patients does not benefit from the use of anti-epidermal growth factor receptor ( EGFR ) treatment although in the absence of a mutation of the K-RAS gene . Preliminary observations suggested that HER-3 , insulin-like growth factor-1 ( IGF-1 ) , nuclear factor-kB ( NF-kB ) and EGFR gene copy number ( GCN ) might identify patients not likely to benefit from anti-EGFR therapy . We tested the interaction between HER-3 , IGF-1 , NF-kB , EGFR GCN and K-RAS mutational analysis to verify the relative ability of these variables to identify a subgroup of patients more likely to benefit from EGFR-targeted treatment among those harbouring a K-RAS wild-type status . PATIENTS AND METHODS We retrospectively collected tumours from 168 patients with metastatic colorectal cancer treated with irinotecan-cetuximab . K-RAS was assessed with direct sequencing , EGFR amplification was assessed by chromogenic in situ hybridisation ( CISH ) and HER-3 , IGF-1 and NF-kB were assessed by immunohistochemistry . RESULTS In patients with K-RAS wild-type tumours , the following molecular factors result ed independently associated with response rate : HER-3 [ odds ratio (OR)=4.6 , 95 % confidence interval ( CI ) 1.8 - 13.6 , P=0.02 ] , IGF-1 ( OR=4.2 , 95 % CI 2 - 10.2 , P=0.003 ) and EGFR GCN ( OR=4.1 , 95 % CI 1.9 - 26.2 , P=0.04 ) . These factors also independently correlated with overall survival as follows : HER-3 [ hazard ratio (HR)=0.4 , 95 % CI 0.28 - 0.85 , P=0.008 ] , IGF-1 ( HR=0.47 , 95 % CI 0.24 - 0.76 , P<0.0001 ) and EGFR GCN ( HR=0.59 , 95 % CI 0.22 - 0.89 , P=0.04 ) . DISCUSSION We believe that our data may help further composing the molecular mosaic of EGFR-resistant tumours . The role of HER-3 , IGF-1 and CISH EGFR GCN should be prospect ively vali date d in clinical trials investigating anti-EGFR treatment strategies in colorectal cancer patients |
2,204 | 26,903,052 | Serum fibrosis markers such as TGF-β1 , collagen I , IV , TIMP-1 , and MMP2 were significantly reduced in the intervention group .
No significant difference was found in serum creatinine levels between the intervention and control groups , and significant renal dysfunction was not observed after administration of RAS inhibitors .
Conclusions RAS inhibitors are potential therapeutic agents for hepatic fibrosis , which can be safely used in patients with chronic liver disease | Background and aims The renin – angiotensin system ( RAS ) has an important role in hepatic fibrosis and portal hypertension .
RAS inhibitors are already accepted in clinical fields for antihypertensive management , but their effects on hepatic fibrosis are controversial .
The aim of this study was to systematic ally review the effects of RAS inhibitors on hepatic fibrosis based on histological assessment . | Background / Aims Angiotensin receptor blockers ( ARBs ) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance . This study compared the effects of combined treatment using the ARB c and esartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospect i ve , r and omized controlled trial . Methods Between January 2008 and July 2009 , 53 cirrhotic patients with clinical ly significant portal hypertension were r and omized to receive either c and esartan and propranolol combination therapy ( 26 patients ) or propranolol monotherapy ( 27 patients ) . Before and 3 months after the administration of the planned medication , the hepatic venous pressure gradient ( HVPG ) was assessed in both groups . The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached , and the c and esartan dose was fixed at 8 mg qd . The primary endpoint was the HVPG response rate ; patients with an HVPG reduction of > 20 % of the baseline value or to < 12 mmHg were defined as responders . Results The mean portal pressure declined significantly in both groups , from 16 mmHg ( range , 12 - 28 mmHg ) to 13.5 mmHg ( range , 6 - 20 mmHg ) in the combination group ( P<0.05 ) , and from 17 mmHg ( range , 12 - 27 mmHg ) to 14 mmHg ( range , 7 - 25 mmHg ) in the propranolol monotherapy group ( P<0.05 ) . However , the medication-induced pressure reduction did not differ significantly between the two groups [ 3.5 mmHg ( range , -3 - 11 mmHg ) vs. 3 mmHg ( range , -8 - 10 mmHg ) , P=0.674 ] . The response rate ( 55.6 % vs. 61.5 % , P=0.435 ) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups . Conclusions The addition of c and esartan ( an ARB ) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension , and is thus not recommended Background Therapies that can slow the progression of liver fibrosis in chronic liver disease are needed . Evidence suggests that the renin-angiotensin system ( RAS ) contributes to inflammation and fibrosis in chronic liver disease . Both animal and limited human studies have shown that RAS inhibition with angiotensin-converting enzyme inhibitors ( ACEi ) and angiotensin receptor-1 [ AT-1 ] blockers ( ARBs ) has antifibrogenic properties . Aims In this study , we evaluated the effects of continuous ACEi/ARB use for 3.5 years on histological liver fibrosis progression in the HALT-C Trial cohort . Methods In the HALT-C Trial , subjects with chronic hepatitis C and advanced hepatic fibrosis ( Ishak stage ≥3 ) underwent serial liver biopsies at baseline , 1.5 years , and 3.5 years after r and omization . The primary outcome was a ≥2-point increase in Ishak fibrosis score in at least one of the two serial biopsies . Sixty-six subjects were continuously taking ACEi/ARBs over the observation period , 126 were taking other antihypertensive medications , and 343 subjects took no antihypertensive medications . Results The three groups were similar in baseline fibrosis scores , and the two groups being treated with antihypertensives were taking a similar number of antihypertensive medications . Fibrosis progression occurred in 33.3 % of the ACEi/ARB group , 32.5 % of the other antihypertensive medications group , and in 25.7 % of subjects taking no antihypertensive medications . No significant associations between ≥2-point increases in fibrosis scores and continuous ACEi/ARB use were apparent at either 1.5 or 3.5 years in diabetes-adjusted and unadjusted odds ratios . Conclusions ACEi/ARB therapy did not retard the progression of hepatic fibrosis BACKGROUND Recent studies have shown that the renin-angiotensin system is implicated in hepatic fibrogenesis in vitro and in vivo . However , no study was done in humans with alcoholic liver disease . AIM To investigate the antifibrotic effect of angiotensin II type 1 receptor ( AT1-R ) blocking agents ( ARB ) in patients with alcoholic liver disease . METHODS The primary outcome was improvement in patients ' histological features . Eighty-five patients with compensated alcoholic liver fibrosis ( ≥ F2 ) which was confirmed by baseline liver biopsy were r and omized ( intention-to-treat ( ITT ) ) to receive either ARB , c and esartan ( 8 mg/day ) with ursodeoxycholic acid ( UDCA ) ( 600 mg/day ) ( n = 42 ) or UDCA alone ( n = 43 ) as control for 6 months and follow-up liver biopsies were conducted . RESULTS According to the Laennec fibrosis system , c and esartan showed significantly higher rates of histological improvements ( ITT , 33.3 % vs. 11.6 % , P = 0.020 ) . In addition , the fibrosis score was significantly reduced from 3.4 ± 1.4 to 3.1 ± 1.5 ( P = 0.005 ) in the c and esartan group . C and esartan also reduced the area of fibrosis and α-smooth muscle actin positive from 11.3 ± 6.0 to 8.3 ± 4.7 and 28.7 ± 10.5 to 23.9 ± 10.3 ( % ) , and the hydroxyproline levels ( μg/g liver tissue ) from 7.8 ± 2.4 to 6.3 ± 1.7 respectively ( P < 0.05 ) . In addition , the relative expression of transforming growth factor-β1(TGF-β1 ) , collagen-1 , AT1-R , tissue inhibitor of metalloproteinase 1 ( TIMP-1 ) , metalloproteinases2 ( MMP2 ) , Rac1 and p22phox by real-time RT-PCR decreased in the c and esartan group ( P < 0.05 ) . Mean arterial blood pressure in the c and esartan group decreased mildly but significantly ( P < 0.001 ) . No significant complications and side effects were observed during the present study . CONCLUSIONS Administration of ARB in compensated alcoholic liver disease induces improvement of fibrosis in histological and quantitative measurements |
2,205 | 26,880,231 | Implementation of sentinel lymph node biopsy in patients with tumours not exceeding 4 cm is safe and efficiently eliminates redundant groin dissections . | This review provides guidelines and aims to estimate utilisation rates of treatment modalities applied in vulvar cancer .
Current st and ards of treatment are as follows : wide local excision instead of radical vulvectomy in the case of small tumour ( T < 2 cm ) , no lymph node dissection in the case of a micro-invasive tumour ( invasion < 1 mm ) , unilateral lymph node dissection in the case of a lateral tumour and inguinal-femoral lymphadenectomy by separate incisions instead of en bloc inguinal-femoral lymph node excision .
Pre-operative treatment with chemoradiotherapy reduces tumour size and improves surgical excision of inoperable primary tumours or fixed lymph nodes , but side effects are considerable . | PURPOSE A subset of head and neck cancers is associated with the human papillomavirus ( HPV ) . Viral infection is closely correlated with expression of p16(INK4A ) in these tumors . We evaluated p16(INK4A ) as a prognostic marker of treatment response and survival in a well-defined and prospect ively collected cohort of patients treated solely with conventional radiotherapy in the Danish Head and Neck Cancer Group ( DAHANCA ) 5 trial . PATIENTS AND METHODS Immunohistochemical expression of p16(INK4A ) was analyzed in pretreatment paraffin-embedded tumor blocks from 156 patients treated with conventional primary radiotherapy alone . The influence of p16(INK4A ) status on locoregional tumor control , disease-specific survival , and overall survival after radiotherapy was evaluated . RESULTS p16(INK4A ) positivity was found in 35 tumors ( 22 % ) . Tumor-positivity for p16(INK4A ) was significantly correlated with improved locoregional tumor control ( 5-year actuarial values 58 % v 28 % ; P = .0005 ) , improved disease-specific survival ( 72 % v 34 % ; P = .0006 ) , and improved overall survival ( 62 % v 26 % ; P = .0003 ) . In multivariate analysis , p16(INK4A ) remained a strong independent prognostic factor for locoregional failure ( hazard ratio [ HR ] , 0.35 ; 95 % CI , 0.19 to 0.64 ) , disease-specific death ( HR , 0.36 ; 95 % CI , 0.20 to 0.64 ) , and overall death ( HR , 0.44 ; 95 % CI , 0.28 to 0.68 ) . CONCLUSION Expression of p16(INK4A ) has a major impact on treatment response and survival in patients with head and neck cancer treated with conventional radiotherapy PURPOSE To investigate the safety and clinical utility of the sentinel node procedure in early-stage vulvar cancer patients . PATIENTS AND METHODS A multicenter observational study on sentinel node detection using radioactive tracer and blue dye was performed in patients with T1/2 ( < 4 cm ) squamous cell cancer of the vulva . When the sentinel node was found to be negative at pathologic ultrastaging , inguinofemoral lymphadenectomy was omitted , and the patient was observed with follow-up for 2 years at intervals of every 2 months . Stopping rules were defined for the occurrence of groin recurrences . RESULTS From March 2000 until June 2006 , a sentinel node procedure was performed in 623 groins of 403 assessable patients . In 259 patients with unifocal vulvar disease and a negative sentinel node ( median follow-up time , 35 months ) , six groin recurrences were diagnosed ( 2.3 % ; 95 % CI , 0.6 % to 5 % ) , and 3-year survival rate was 97 % ( 95 % CI , 91 % to 99 % ) . Short-term morbidity was decreased in patients after sentinel node dissection only when compared with patients with a positive sentinel node who underwent inguinofemoral lymphadenectomy ( wound breakdown in groin : 11.7 % v 34.0 % , respectively ; P < .0001 ; and cellulitis : 4.5 % v 21.3 % , respectively ; P < .0001 ) . Long-term morbidity also was less frequently observed after removal of only the sentinel node compared with sentinel node removal and inguinofemoral lymphadenectomy ( recurrent erysipelas : 0.4 % v 16.2 % , respectively ; P < .0001 ; and lymphedema of the legs : 1.9 % v 25.2 % , respectively ; P < .0001 ) . CONCLUSION In early-stage vulvar cancer patients with a negative sentinel node , the groin recurrence rate is low , survival is excellent , and treatment-related morbidity is minimal . We suggest that sentinel node dissection , performed by a quality -controlled multidisciplinary team , should be part of the st and ard treatment in selected patients with early-stage vulvar cancer BACKGROUND The improved prognosis for patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma ( HNSCC ) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a prospect i ve clinical trial . METHODS We prospect ively evaluated the association of tumor HPV status with therapeutic response and survival among 96 patients with stage III or IV HNSCC of the oropharynx or larynx who participated in an Eastern Cooperative Oncology Group ( ECOG ) phase II trial and who received two cycles of induction chemotherapy with intravenous paclitaxel and carboplatin followed by concomitant weekly intravenous paclitaxel and st and ard fractionation radiation therapy . The presence or absence of HPV oncogenic types in tumors was determined by multiplex polymerase chain reaction ( PCR ) and in situ hybridization . Two-year overall and progression-free survival for HPV-positive and HPV-negative patients were estimated by Kaplan-Meier analysis . The relative hazard of mortality and progression for HPV-positive vs HPV-negative patients after adjustment for age , ECOG performance status , stage , and other covariables was estimated by use of a multivariable Cox proportional hazards model . All statistical tests were two-sided . RESULTS Genomic DNA of oncogenic HPV types 16 , 33 , or 35 was located within tumor cell nuclei of 40 % ( 95 % confidence interval [ CI ] = 30 % to 50 % ) of patients with HNSCC of the oropharynx or larynx by in situ hybridization and PCR . Compared with patients with HPV-negative tumors , patients with HPV-positive tumors had higher response rates after induction chemotherapy ( 82 % vs 55 % , difference = 27 % , 95 % CI = 9.3 % to 44.7 % , P = .01 ) and after chemoradiation treatment ( 84 % vs 57 % , difference = 27 % , 95 % CI = 9.7 % to 44.3 % , P = .007 ) . After a median follow-up of 39.1 months , patients with HPV-positive tumors had improved overall survival ( 2-year overall survival = 95 % [ 95 % CI = 87 % to 100 % ] vs 62 % [ 95 % CI = 49 % to 74 % ] , difference = 33 % , 95 % CI = 18.6 % to 47.4 % , P = .005 , log-rank test ) and , after adjustment for age , tumor stage , and ECOG performance status , lower risks of progression ( hazard ratio [ HR ] = 0.27 , 95 % CI = 0.10 to 0.75 ) , and death from any cause ( HR = 0.36 , 95 % CI = 0.15 to 0.85 ) than those with HPV-negative tumors . CONCLUSION For patients with HNSCC of the oropharynx , tumor HPV status is strongly associated with therapeutic response and survival PURPOSE To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer . PATIENTS AND METHODS Eligible women had squamous cell carcinoma , at least 1-mm invasion , and tumor size ≥ 2 cm and ≤ 6 cm . The primary tumor was limited to the vulva , and there were no groin lymph nodes that were clinical ly suggestive of cancer . All women underwent intraoperative lymphatic mapping , sentinel lymph node biopsy , and inguinal femoral lymphadenectomy . Histologic ultra staging of the sentinel lymph node was prescribed . RESULTS In all , 452 women underwent the planned procedures , and 418 had at least one sentinel lymph node identified . There were 132 node-positive women , including 11 ( 8.3 % ) with false-negative nodes . Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node . The sensitivity was 91.7 % ( 90 % lower confidence bound , 86.7 % ) and the false-negative predictive value ( 1-negative predictive value ) was 3.7 % ( 90 % upper confidence bound , 6.1 % ) . In women with tumor less than 4 cm , the false-negative predictive value was 2.0 % ( 90 % upper confidence bound , 4.5 % ) . CONCLUSION Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva |
2,206 | 10,683,589 | A meta- analysis of five reports comparing a hydrocolloid dressing with a traditional treatment suggested that treatment with the hydrocolloid result ed in a statistically significant improvement in the rate of pressure sore healing .
There was no difference in the proportion of ulcers healed between patients treated with cryopreserved cultured allografts or a hydrocolloid , though the former-treated ulcers had a higher rate of epithelialisation .
A collagen dressing was more effective than treatment with daily antiseptic .
However , publication bias was indicated in a comparison of traditional and hydrocolloid dressings .
Implication for practice : There is little evidence to indicate which dressings or topical agents are the most effective in the treatment of chronic wounds .
However , there is evidence that hydrocolloid dressings are better than wet-to-dry dressings for the treatment of pressure sores .
In the treatment of venous ulcers , low adherent dressings are as effective as hydrocolloid dressings beneath compression b and aging . | Background .
Wound dressings are design ed to keep the wound clean and free from contamination and also to promote wound healing , particularly in chronic wounds where there may be significant tissue loss .
This review evaluates the evidence for effectiveness and cost-effectiveness of dressings and topical preparations in pressure sores , leg ulcers and surgical wounds healing by secondary intention . | Leg ulcers are a chronic manifestation of sickle-cell disease ( SCD ) and are often painful , disabling , and difficult to treat . RGD peptide matrix treatment is a novel therapy design ed to provide a topical synthetic extracellular matrix that can act as a temporary substitute for the damaged natural matrix at the ulcer site . In this r and omized , placebo-controlled , double-blind , prospect i ve , multicenter investigation , SCD patients with full-thickness leg ulcers were treated with st and ard therapy plus RGD peptide matrix or saline placebo once weekly for up to 10 weeks . Healing in patients with chronic ulcers ( 2 months or greater in duration ) was significantly accelerated ( P = .0085 ) in RGD peptide matrix recipients compared with the placebo group . In these chronic ulcer cases , the average percent ulcer closure ( decrease in ulcer surface area ) in the RGD peptide matrix group ( 54.4 % + /- 8.9 % ) exceeded that in the placebo group ( 19.0 % + /- 24.3 % ) nearly threefold by study endpoint . Furthermore , RGD peptide matrix was equally effective in promoting healing of long persistent ulcers and ulcers of shorter duration . In contrast , st and ard therapy plus placebo was significantly less effective ( P = .001 ) in promoting healing for ulcers of progressively greater duration . The results of this study provide preliminary evidence that RGD peptide matrix treatment may significantly accelerate healing of chronic sickle-cell leg ulcers A new dressing for chronic wounds , BioFilm hydrogel dressing , was compared to a hydrocolloid dressing ( HCD ) control in a clinical trial involving 90 patients and 129 Stage I and II wounds ( defined by Enis and Sarmienti ) . The testing sites included both acute care and extended care facilities . A comparison of healing response and functional characteristics of both dressings was part of this assessment . Biofilm dressings demonstrated a healing advantage over the HCD . In addition , clinicians judged that the hydrogel dressings were easier to use and had superior fluid management capability and product integrity with minimal disruption to the healing wounds The author reports an open controlled trial on 72 patients affected by different types of skin ulcers , in which a heterologous lyophilized collagen sponge was compared with Dextranomer as healing adjuvant . The rationale of use and pharmacological properties of this collagen are outlined and explain its outst and ing results 1 . Topical irrigation with normal saline is known to produce rapid healing in chronic leg ulcers . This study was design ed to determine if the rate of healing could be improved by the addition of topical nutrition to the irrigating solution . 2 . Forty-eight patients with chronic leg ulcers were admitted to hospital for a minimum of 6 weeks bed-rest . During this time the ulcers were continuously irrigated by one of four test solutions . The solutions were : normal saline ; a dilute amino acid solution isotonic with the normal saline ; a hyperosmolar saline solution ; a hyperosmolar amino acid solution . There were 12 ulcers in each group . 3 . The amino acid solutions produced significantly faster healing than the saline solutions ( P less than 0.01 ) . Concentration had no significant effect on healing ( P greater than 0.15 ) . 4 . The application of amino acids does appear to enhance healing in this model of delayed wound healing . This effect does not depend only on the osmolarity of the solution used Applications of Condress ( patented sheets of pure bovine collagen ) on open skin surfaces ( 30 cases of " ulcus cruris " , 5 cases of decubitus , and malum perforans ; 10 cases of full-thickness burns ) were examined in a controlled trial . Quantification of regeneration speed , macrophotographic survey of granulation tissue and epithelial border , thermographic and chromometric evaluation of the skin microcirculation , and histological observation of regenerating tissues , were the parameters used . The following results were obtained : marked reduction of healing time , different aspects of the granulation-tissue responses , different times of topical collagenolysis , increased vascular perfusion , histological activation of angiogenesis , fibrogenesis , histiomacrophage function and superficial absorption . The employment of Condress in burn areas seems to be highly promising In a prospect i ve , r and omised , controlled trial of 92 patients with full-thickness pressure ulcers , the efficacy of an alginate wound dressing was compared to that of an established local treatment with dextranomer paste . During treatment , a minimal 40 % reduction in wound area was obtained in 74 % of the patients in the alginate group and in 42 % of those in the dextranomer group . The median time taken to achieve this goal was four weeks with alginate and more than eight weeks in the control group . Mean surface area reduction per week was 2.39cm2 ( sd 3.54 ) and 0.27cm2 ( sd 3.21 ) in the alginate and dextranomer groups respectively ( p=0.0001 ) . This difference was still highly significant when the sub-groups of almost completely healed subjects at the end of the study were considered . This striking healing efficacy of an alginate dressing suggests it possesses pharmacological properties which require further investigation Cultured epidermal allografts have been successfully used to treat a wide variety of skin defects ranging from burns to leg ulcers . Their postulated mechanism of action is through release of multiple cytokines that stimulate epithelialization from the wound periphery as well as from remnant epidermal appendages . A r and omized , controlled clinical trial was undertaken to compare the efficacy of cryopreserved cultured allograft dressings ( CCAD ) with tulle-gras dressings in the treatment of split-skin graft donor sites . Five patients were enrolled in the study and in each patient , half of the donor site was allografted and the other half was treated with tulle-gras control . The mean time to complete healing was 6.2 days for CCAD compared with 9.6 days ( p = 0.035 ) for the tulle-gras controls . Patient assessment of pain with dressing changes was also significantly lower at the CCAD-treated sites than at the control sites ( p = 0.001 ) . The results indicate that cultured allografts offer greater patient comfort and earlier maturation of regenerated skin The first r and omized , blinded , placebo-controlled human trials of recombinant basic fibroblast growth factor ( bFGF ) for pressure sore treatment were performed . Three different concentrations of bFGF in five dosing schedules were tested for safety using hematology , serum chemistries , urinalysis , absorption , antibody formation , and signs of toxicity . Efficacy was evaluated by wound volumes , histology , and photography . No toxicity , significant serum absorption , or antibody formation occurred . In six of eight subgroups , there was a trend toward efficacy with bFGF treatment . When all subgroups were combined , comparison of the slopes of the regression curves of volume decrease over initial pressure sore volume demonstrated a greater healing effect for the bFGF-treated patients ( p < 0.05 ) . Histologically , bFGF-treated wound sections demonstrated increased fibroblasts and capillaries . More patients treated with bFGF achieved > 70 % wound closure ( p < 0.05 ) . Blinded observers were able to distinguish differences in visual wound improvement between bFGF and placebo groups . These data suggest that bFGF may be effective in the treatment of chronic wounds A total of 67 patients with pressure ulcers were r and omized into one of three treatment modalities : hydrogel sheet dressing , hydrocolloid , or wet-to-moist gauze . Safety , efficacy , and physical attributes of the three dressings were evaluated . No statistical significance was found in wound healing rate among the three treatments . Hydrogel sheets were advantageous in allowing wound visualization without dressing or wound disruption Interleukin-1beta is produced by numerous cell types including monocytes and fibroblasts . It has been shown to stimulate multiple cell types including fibroblasts , keratinocytes , endothelial cells , neutrophils , macrophages , and lymphocytes . Previously , interleukin-1beta was shown to accelerate healing in partial-thickness and full-thickness wounds in animals and was also shown to be safe when applied topically in Phase I human trials . Therefore a prospect ively r and omized , blind , placebo-controlled trial was performed with patients with chronic pressure ulcers . Doses of interleukin-1beta of .01 microg , .10 microg , and 1.0 microg per square centimeter did not show acceleration of healing of the pressure ulcers . Therefore use of recombinant human interleukin-1beta in this study was safe but , at the dose levels tested , did not result in improvement in the healing ratio OBJECTIVE To assess the effect of different dressings on venous ulcer healing . DESIGN A r and omised clinical trial . MATERIAL S Patients were r and omised to treatment with one of three dressings : a zinc oxide impregnated b and age , a zinc oxide impregnated stockingette , or an alginate dressing . All patients were treated as out patients and had compression b and aging with two minimal stretch b and ages ( Elastocrepe ) and a stockingette ( Tubigrip ) to keep the b and ages in place . METHODS One hundred and thirteen patients ( 133 ulcerated limbs ) with chronic ulceration of the leg due to venous disease alone , and attending Fremantle Hospital Leg Ulcer Clinic , Western Australia were entered into the study . Healing was measured as complete healing of the ulcerated limb or failure of the limb to heal within 9 months . RESULTS There was no significant difference between the three groups in ulcer size , duration , and other parameters compared . Healing was affected significantly by ulcer size and which leg was ulcerated . There was significantly faster healing with the paste b and age . CONCLUSION The use of a paste b and age significantly improved the healing of chronic venous ulcers when used in combination with compression b and aging , and compared to an alginate dressing and a zinc oxide impregnated stockingette OBJECTIVE To determine the efficacy of the daily topical application of recombinant platelet-derived growth factor-BB ( rPDGF-BB ) , a recognized vulnerary agent , in the treatment of deep pressure ulcers . DESIGN Prospect i ve , r and omized , double-blind trial . SETTING Patients were treated in a nursing home or a hospital setting before transfer to a nursing home . PATIENTS Eligibility criteria included a clean pressure ulcer that had been adequately debrided and the absence of severe cardiac , pulmonary , or renal conditions . The causes of the ulcers were not related to a venous or arterial vascular disorder . The patients were elderly ( mean age , 68 to 74 years ) . INTERVENTIONS After r and omization , patients were given daily topical aqueous rPDGF-BB ( dosage , 100 or 300 micrograms/mL ) or placebo and saline gauze dressings were applied daily in addition to frequent turning . MAIN OUTCOME MEASURE Serial volume measurements of the healing wounds were taken using alginate molds . RESULTS The ulcers of 41 patients were analyzed . At the end of 28 days , median ulcer volumes had decreased to 83 % , 29 % , and 40 % of the initial size in the groups receiving placebo , rPDGF-BB , 100 micrograms/dL , and rPDGF-BB , 300 micrograms/mL , respectively . When adjusted for initial volume , ulcer volume after 28 days of treatment was smaller in the rPDGF-BB-treated groups compared with the placebo group ( analysis of covariance , P = .056 ) . Ulcers in the two rPDGF-BB-treated groups were significantly smaller in volume compared with those in the placebo group , using a linear contrast procedure . CONCLUSIONS Data from this small trial suggest that local application of rPDGF-BB may be of therapeutic benefit in accelerating the healing of chronic pressure ulcers We performed a r and omized , double‐blind study of the efficacy of locally applied zinc oxide on the healing of leg ulcers . Thirty‐seven geriatric patients , nineteen with arterial and eighteen with venous leg ulcers , were treated either with a gauze compress medicated with zinc oxide ( 400 μg ZnO/cm2 ) or with an identical compress without zinc oxide . The treatment was assessed from ulcer size measurements and the presence or abscncc of granulation and ulcer debridement over a period of 8 weeks . The zinc‐treated patients ( 83 % success rate ) responded significantly better ( P < 0·05 ) than the placebo‐treated patients ( 42 % success rate ) . The results suggest that healing of leg ulcers is improved after the addition of zinc oxide to the local regimen To determine the effect of bacterial colonization on venous ulcer healing , 82 patients with 100 venous ulcerated limbs were each studied prospect ively for six months . Despite bacteriological swab results , topical or systemic antibiotics were not administered unless cellulitis supervened . Initial ulcer size , length of ulcer history and time to complete healing of colonized and uncolonized ulcers were determined and compared OBJECTIVE To compare the clinical effectiveness and wound management properties of a copolymer membrane , Inerpan ( Synthélabo ) , and a hydrocolloid dressing , Comfeel ( Coloplast ) , in the treatment of decubitus ulcers in the elderly . DESIGN Open , r and omized , multicentric French study , with two parallel groups of patients . PATIENTS 168 in- patients aged more 65 years ( mean age : 82 years ) suffering from grade II to grade IV ( in the Shea classification ) pressure sores . TRIAL PERIOD : Either 8 weeks or until the ulcer healed , whichever occurred first . MEASUREMENTS In addition to a complete physical examination , patients were evaluated at baseline for nutritional status and risk factors . The wounds were described , their depth scored , and the areas traced at Weeks 0 , 1 , 2 , 4 , 6 , and 8 . The number of dressings used was recorded . RESULTS Thirty-one Inerpan-treated patients and 23 Comfeel-treated patients achieved healing ( P = 0.089 ) , with respective median healing times of 32 and 38 days . Healing times were compared using survival curves ( in the whole population ) adjusted for ulcer depth effect and showed a significant difference in favor of Inerpan ( P = 0.044 and 0.014 ) . Progress of healing ( percentage of ulcer healed ) was calculated in the two groups . Clinical ly assessed the treatment performance scored at the completion of the study showed better results with Inerpan ( P < 0.05 ) . Both groups were similar in terms of granulation/exudation scores , surrounding skin , and ease of care . CONCLUSION It is concluded that Inerpan is easy to use , safeguards the healing process , and is of particular value in the management of pressure sores A great deal of interest has been focused recently on the potential use of synthetic polypeptide growth factors to stimulate healing of chronic wounds . In this pilot double-blind r and omized study conducted at a single center , we used human recombinant epidermal growth factor ( h-EGF ) to treat 44 patients with venous ulceration of the lower extremities . An aqueous solution ( 10 micrograms/mL ) of h-EGF was applied topically to the ulcers twice a day until healing occurred or for a maximum of 10 weeks . Patients were evaluated weekly for measurements of ulcer size and for the formation of granulation tissue suitable for grafting . Nine patients were excluded from efficacy evaluation because of protocol violations . Therefore , 35 patients ( 17 h-EGF , 18 placebo ) were evaluable for efficacy , and 44 patients ( 22 h-EGF , 22 placebo ) were available for safety . The median baseline ulcer size for all patients was 18.5 cm2 , and was not significantly different between h-EGF and placebo group ( 12.9 cm2 versus 19.2 cm2 , respectively , P = .27 ) . By study end , six ( 35 % ) of h-EGF treated patients and two ( 11 % ) in the placebo group had healed completely ( P = .10 ) . Another 6 patients ( 2 of 17 h-EGF , 4 of 18 placebo ; P = .50 ) developed healthy granulation tissue that was suitable for grafting . The median ulcer size reduction was 7 % for h-EGF versus 3 % for placebo per week ( P = .29 ) , and 73 % versus 33 % at study end ( P = .32 ) . No untoward side effects were related to the application of h-EGF . We conclude that topical application of h-EGF , in the dose and manner used in this study , was safe but failed to significantly enhance re-epithelialization of venous ulcers . However , a greater reduction in ulcer size and a larger number of healed ulcers with the use of h-EGF are encouraging results In a r and omized , double-blind , placebo controlled study in patients with venous leg ulcers , the efficacy and tolerability of topical applications of a prostacylin hydrogel ( iloprost ) was investigated . 34 patients were allocated to the placebo treatment and 65 patients were allocated to the iloprost treatment . The iloprost treatment commenced with 10 micrograms/ml for the first 3 days and was increased to 40 micrograms/ml for the remaining treatment period if well tolerated . Maximally 3 ml of the hydrogel were applied daily on the ulcer base for a period of 8 weeks . The total area of the ulcers at the last individual assessment was chosen as the main criterion for evaluation of efficacy . Both concentrations of iloprost were well tolerated with almost the entire trial population on iloprost being treated with the 40 micrograms/ml iloprost hydrogel . With regards to efficacy , no significant difference was found in favour of the iloprost treatment Methods for measuring wound size and healing have ranged from simple measurement with a ruler to sophisticated automated image analysis . As part of a multicenter , double-blind evaluation of a growth factor for wound healing , we evaluated the predictability and accuracy of two measurement systems . Four hundred and fifty paired comparisons ( 900 observation points ) of lower extremity ulcers of either diabetic or venous stasis origin were evaluated weekly for at least four weeks . Wound size was determined by computer digitization of either color slide photographs ( photo method ) or acetate tracings ( tracing method ) . Measurements of wound surface area for both methods were very similar , with a correlation coefficient of 0.97 . The st and ard deviation of the methods , stratified by wound size and study center , were low ( 10 percent to 20 percent ) . Inter-site variability accounted for only 5.4 percent of the total variability noted in these observations . We have found that both the photo method and the tracing method may be useful in large , multi-center clinical trials when measurements of wound size are utilized to evaluate responsiveness to therapy Two occlusive dressings -- one zinc oxide medicated ( Mezinc ) and one hydrocolloid (Duoderm)--were compared in a prospect i ve , r and omized trial over a period of 8 weeks to determine their healing ability and effect on pain for venous and arterial leg ulcers . All patients were patch-tested before the study and colophony allergy was an exclusion criterion . Of the 43 out patients included , 31 completed the trial and 6 patients r and omized to each treatment group were withdrawn . The initial ulcer areas decreased after 8 weeks of treatment with Mezinc by 64 % and by 48 % after treatment with Duoderm . Ulcer pain was relieved in 50 % of the patients --with a similar analgesic effect for the two dressings . Mezinc treatment was discontinued in 2 cases due to sensitization to colophony ( one ingredient of Mezinc ) which indicated a risk of contact allergy to colophony due to Mezinc treatment . 1103 consecutive eczema patients were patch-tested on the back with Mezinc and colophony 20 % in petrolatum simultaneously . It was found that 42 ( 4 % ) of the patients showed allergic skin reactions to colophony and 19 ( 2 % ) to Mezinc . Both dressings were well tolerated by leg ulcer patients and there appeared to be no major differences in the efficacy of the two occlusive dressings The aim of this study was to investigate whether cultured autologous mononuclear cells ( MNC ) effectively initiate , accelerate and improve granulation and epithelialisation of skin ulcers . Thirty-three patients with chronic arterial occlusive disease ( CAOD ; n = 21 ) or venous post-thrombotic syndrome ( PTS ; n = 12 ) were treated with autologous MNC and compared with a control group of 30 patients who received tissue culture medium alone . Previous treatments had been unsuccessful for a mean of 9.23 ( 3 - 19 ) months . MNC were harvested from the peripheral blood of each patient by st and ard techniques , cultured for three days and applied to the ulcer twice a week . After 4.6 + /- 1.9 weeks , 29/33 ulcers were closed in the MNC group . Patients in the control group took 8.1 + /- 1.2 weeks for 17/30 ulcers . Thus ulcer healing was significantly speedier with MNC seeding ; 48 % of all ulcers were closed after 30 days of MNC treatment and 92 % after 60 days . Patients with PTS responded significantly faster than patients with CAOD . In 90 % of patients with painful ulcers MNC treatment result ed in pain relief , whereas in the control group only 50 % of patients became pain-free Seventy patients with 90 venous ulcers were r and omly assigned to hydrocolloid or conventional dressing and compression therapy at four study centers . The ulcers had been present for a mean of 47.8 in the control and 46.2 weeks in the treatment group and 42 % of all patients had recurrent ulcers . Ulcers treated with hydrocolloid dressings reduced 71 % and control treated wounds reduced 43 % in area after 7.2 weeks of treatment . Thirty-four percent of all ulcers healed . Mean time to healing was 7 weeks for the hydrocolloid dressing group and 8 weeks for the control group . Most ulcers were less painful at final evaluation , but reduction in pain was more pronounced in hydrocolloid-dressed ulcers ( p=0.03 ) . At baseline as well as during follow-up , significant differences between study centers were observed . Ulcers in patients in the United Kingdom were larger and less likely to heal ( p=0.001 ) . Size of the ulcer at baseline was associated with treatment response and time to healing ( p=0.002 ) . Percent reduction in ulcer area after 2 weeks was also correlated with treatment outcome ( p=0.004 ) and time to healing ( p=0.002 ) . When all treatment outcome predictors were analyzed together , only percent reduction in area after 2 weeks remained statistically significant ( p=0.002 ) , with percent reduction during the first 2 weeks of treatment > 30 % predicting healing To compare the efficacy and the cost-effectiveness of moist gauze dressings and a hydrocolloid wafer dressing ( DuoDERM CGF ) , 70 patients with 97 pressure ulcers that were stage II and /or stage III were r and omly assigned to one of two treatment methods : moist gauze dressings or hydrocolloid dressings . Efficacy was defined as the number of ulcers that completely healed . In this debilitated , poorly nourished group of patients , one ulcer completely healed in the moist gauze dressing group , and 11 healed in the hydrocolloid group . The per diem cost of the moist gauze dressing was $ 12.26 ; the per diem cost of the hydrocolloid dressing was $ 3.55 In an attempt to improve the management of the perineal wound after abdominoperineal excision of the rectum we have assessed the value of foam elastomer , a catalysed silicone polymer dressing . This substance has already been used successfully in the treatment of open , granulating wounds at other sites ( 1 ) This r and omized double‐blind controlled study examined whether sulphydryl‐containing agents influence the healing of venous ulceration occurring for the first time on the medial side of the leg . Graduated compression b and aging , which exerted a mean ankle pressure of 40·6 ±0·4 mmHg , and a mean below‐knee pressure of 17·1 ±0·2 mmHg , healed 70 % of ulcers within 12 weeks ( n= 46 ) . The addition of the sulphydryl‐containing agents dl‐cysteine ( n=46 ) or dl‐methionine‐methyl sulphonium chloride ( n= 45 ) to the compression b and aging ( daily application of the powder for 7 days , followed by once weekly applications until the end of the study 3 months later ) significantly ( P < 0·01 ) stimulated healing of venous ulceration relative to control values when studied 4 , 8 and 12 weeks after commencing treatment . After 3 months of treatment , both sulphydryl‐containing compounds healed 93 % of the ulcers . The results show that sulphydryls stimulate healing of venous ulceration The disturbed microcirculation is seen as a causative factor in provoking venous leg ulcers . The stable prostacyclin analogue iloprost has shown beneficial effects on the disturbed microcirculation after intravenous infusions . In this study the topical route was chosen in order to facilitate h and ling and to reduce the possibility of systemic adverse reactions . The aim of this study was to assess the efficacy and tolerability of two concentrations of iloprost solutions ( 0.0005 % and 0.002 % ) . The trial design was a r and omized , double-blind , placebo controlled study in 11 centres in Germany with 49 patients allocated to treatment 1 ( placebo solution ) ; 49 patients to treatment 2 ( 0.0005 % iloprost solution ) and 50 patients to treatment 3 ( 0.002 % iloprost solution ) . The study solutions were applied twice weekly for a period of eight weeks on the ulcer edge and ulcer surrounding . This study failed to show any statistically significant reduction in the ulcer size as a result of the iloprost treatment compared to the placebo treatment . Possible reasons for the findings are discussed The use of a 2 % ointment formulation of ketanserin , an S2-serotoninergic blocking agent , was investigated in a r and omized double-blind clinical trial for its effect on the healing of wounds of patients with decubitus , venous , and ischemic skin ulcers . The result demonstrates a significant difference in favor of the ketanserin-treated group ( 35 patients ) versus the placebo-treated group ( 37 patients ) on the basis of two factors : formation of granulation tissue and epithelialization . In addition , a significant difference of 150 % in the initial velocity of wound closure was observed in favor of the patients treated with ketanserin . This effect was persistent during the entire study period Chronic , nonhealing , cutaneous ulcers are a serious clinical problem . The results of previous studies using platelet-derived wound healing formula ( PDWHF ) , derived from autologous platelets , provided evidence that PDWHF actively stimulates repair of the wound . To test whether or not PDWHF accelerates repair , a prospect ively r and omized , blinded trial was conducted using a placebo control . A total of 32 patients with chronic , nonhealing , cutaneous wounds of the lower extremity were r and omized and treated for eight weeks with PDWHF or placebo . Epithelialization of the wound was the end point of study . In the group who received treatment , 81 per cent of patients had epithelialization in eight weeks compared with 15 per cent in the control group ( p less than 0.0001 ) . After crossover to treatment with PDWHF , all of the patients in the control group had epithelialization in an average of 7.1 weeks . Regression analysis of the rates of epithelialization also showed significant differences during the initial eight week trial and showed no difference after crossover of the control group to therapy with PDWHF . Results from this study demonstrate a highly statistically significant effect of topically applied platelet-derived growth factors on the repair of chronic , nonhealing , cutaneous ulcers Chronic wounds such as venous stasis ulcers have become a socioeconomic problem . Even with successful initial management , the recurrence rate approaches 70 % . With the advent of new wound healing agents , nonoperative attempts to heal these wounds appear indicated . This study reports a prospect i ve r and omized evaluator-blinded trial comparing two potential wound healing agents to an inert vehicle placebo . Eighty-six evaluable patients completed the trial . Silver sulfadiazine 1 % in a cream proved to statistically reduce the ulcer size compared with a biologically active tripeptide copper complex 0.4 % cream formulation or the placebo . There was no difference between the latter two treatments . Silver sulfadiazine has been shown to allow keratinocyte replication and to have antiinflammatory properties . In this trial its antibacterial action was not used since all ulcers had comparable bacterial levels ( less than or equal to 10(5)/gm of tissue ) before treatment . These results suggest that the silver sulfadiazine cream used in this study may facilitate healing in wounds healing largely by the process of epithelialization Seventy-five consecutive patients with pilonidal sinus disease were r and omized to receive either Eusol dressings or Silastic foam dressings . Patients were divided into those with pilonidal sinus and pilonidal abscess . There was no significant difference between time to hospital discharge or time to full healing in either group . The cost benefits and simplicity of Silastic foam dressing are discussed This prospect i ve r and omized study was conducted in the home care setting to compare healing rates and costs of two different dressings for pressure ulcers : the gauze and tape dressing and the transparent moisture vapor permeable dressing ( MVP ) . Demographic variables , healing rates , and cost of treatment were statistically analyzed for 77 pressure ulcers ( 48 patients ) . Each wound was r and omly assigned to either a gauze dressing or a MVP dressing . Initial ulcer grade ( Shea criteria ) and measurements were determined at the start of treatment and weekly for an eight-week period . Photographs of the wound were taken at the beginning and end of treatment . The same protocol for irrigating the wound and relieving pressure was followed for both dressing groups . The median improvement for the grade II group was 100 % for the MVP ( n = 22 ) and 52 % for gauze ( n = 12 ) , p less than 0.05 ( Wilcoxon rank sum test ) . The healing rates for grade III ulcers were not significantly different in the two dressing groups . The mean ( eight-week ) labor and supply cost per ulcer using the MVP was $ 845 , while that for gauze treatments was $ 1359 , p less than 0.05 ( Wilcoxon rank sum test ) . The cost difference for grade III ulcers was not significant in the two dressing groups . The MVP improved the healing rate and was more cost effective for grade II ulcers . Both gauze and MVP dressings proved effective for the treatment of grade III ulcers A r and omized phase I/II double-blind , placebo-controlled study was design ed to evaluate 1 , 10 , and 100 µg/ml ( 0.01 , 0.1 , and 1.0 µg/cm2 ) recombinant human BB homodimeric platelet-derived growth factor ( rPDGF-BB ) applied topically to chronic pressure ulcers for 28 days . Twenty patients were enrolled and completed the trial . No toxicities were associated with rPDGF-BB treatment . Patients treated with 100 µg/ml of rPDGF-BB had a pronounced healing response compared with placebo-treated patients . By day 29 , ulcers treated with 100 µg/ml of rPDGF-BB were smaller in remaining size compared with those of placebo-treated patients when the following specific parameters were measured : percentage of initial depth ( 14.1 ± 7.4 vs. 34.9 ± 6.7 ) and percentage of initial volume ( 6.4 ± 4.0 vs. 21.8 ± 5.6 ) . Histological analyses of biopsies revealed active wound healing processes in all groups with no disruption in the normal healing sequence in rPDGF-BB-treated wounds . The results of this small , descriptive study suggest rPDGF-BB is a potent vulnerary agent for accelerating soft-tissue repair , warranting further study One of the main functions of wound dressings is to control water vapour transmission rate ( WVTR ) from wounded skin . In this paper , the influence of hydrocolloid , knitted viscose and gauze dressings was evaluated through in vivo measurement of WVTR in burns and chronic leg ulcers utilizing an evaporimeter . The results suggest that the evaporative water vapour loss from exposed skin wounds depends mainly on the wound depth , and that chronic leg ulcers have the same level of the WVTR as full thickness burns . Compared with the knitted viscose and gauze dressings , hydrocolloid dressing has a greater effect on reducing evaporative water loss , with WVTR being 20 - 30 % of that of exposed wounds under the conditions used in this study . This result is in agreement with that obtained in an in vitro evaluation The cost effectiveness of using hydrocolloid dressings versus nonsterile saline-gauze wet-to-moist dressings for treatment of pressure ulcers in a long-term care setting was evaluated . During 21 months , 39 subjects were enrolled , and treatment was r and omly assigned . Eighty-nine percent of the hydrocolloid subjects and 86 % of the saline-gauze subjects healed . Median healing time was shorter for the hydrocolloid group ( nine days ) than for the saline-gauze group ( 11 days ) , although the difference did not reach statistical significance ( p = .12 ) . Presence of exu date at baseline was associated with a prolonged time to healing . For the hydrocolloid treatment , the median nursing time was one eighth that of the saline-gauze treatment , but its material s cost was 3.3 times higher . Using local nursing wages , median total cost for treatment with hydrocolloid dressing was $ 15.58 ; for the saline gauze , it was $ 22.65 . Using national nursing wages , these costs were $ 15.90 and $ 25.31 , respectively . The cost savings of the hydrocolloid treatment using local wages did not reach statistical significance . However , using national wages , the cost of the hydrocolloid treatment was significantly less expensive . Nursing home treatment of pressure ulcers was inexpensive overall . Consequently , the absolute cost savings of using hydrocolloid dressings instead of nonsterile saline-gauze dressing , although real , was relatively modest . Physicians can use local nursing wages to calculate the magnitude of savings in their area Because of significant reductions in the Swedish health care budget , the trend in the Swedish health care service is to move patients with leg ulcers out of hospitals and into primary care or community home care . This study compares the costs for a 6-week treatment of patients with leg ulcers in primary care . Subjects were r and omly assigned to one of the two treatment groups -- wet-to-dry saline gauze dressings changed twice a day or a hydrocolloid dressing ( HCD ) DuoDERM changed when needed or once a week . A variety of costs , including travel costs for the nurses , time for dressing changes , and material ( including ancillary items ) were compared In search of a cheaper and effective dressing solution for ulcers , 53 patients presenting with various types of ulcers at the University of Port Harcourt Teaching Hospital were treated with different strengths hypertonic saline 0.3 , 0.9 , 1.2 , 1.5 , 2 and 3 osmoles . The ages of the ulcers were between 3 months and 3 years . Optimal results were obtained with solution of 1.5 mmols and above . Desloughing occurred within 2 weeks and granulation was fast and good enough for skin grafting where necessary . Healing was faster in other ulcers that were not due for grafting We prospect ively followed in patients receiving treatment for pressure sores to identify the better of two local treatment regimens . Twenty-seven patients with 76 pressure sores received treatment with hydrocolloid dressings ( HCDs ) and 25 patients with 52 pressure sores received treatment with Dakin 's solution (chloramine-T)-soaked wet-to-dry dressings . Thirty-eight ( 73 % ) patients initially had severe nutritional depletion . The mean serum albumin value of the pressure sore treatment groups was lower than that of an age-matched group without pressure sores . In the HCD group , 66 ( 86.8 % ) pressure sores improved compared with 36 ( 69.2 % ) pressure sores in the wet-to-dry dressings group . The HCD regimen was more efficacious even in a subgroup of patients who received inadequate nutritional support during treatment . Adequate nutritional intake during the study was associated with better healing in both local treatment groups |
2,207 | 15,674,869 | The increase in mortality with steroids in this trial suggest that steroids should no longer be routinely used in people with traumatic head injury | BACKGROUND Traumatic brain injury is a leading cause of death and disability .
Corticosteroids have been widely used in treating people with traumatic brain injury .
OBJECTIVES To quantify the effectiveness and safety of corticosteroids in the treatment of acute traumatic brain injury . | The conflicting evidence concerning the influence of high-dose steroids on intracranial pressure ( ICP ) and outcome following severe head injury has led to the institution of the prospect i ve double-blind controlled trial reported here . Severely head-injured patients admitted to intensive care during a 3-year period were r and omly allocated to a dexamethasone- or placebo-treated group . Adults in the steroid group received dexamethasone , 50 mg intravenously , as a bolus on admission to the neurosurgical unit , then 100 mg on Days 1 , 2 , and 3 , 50 mg on Day 4 , and 25 mg on Day 5 on continuous intravenous infusion . Children received proportionate intravenous dosages calculated on a weight basis . Severity of head injury was assessed from admission Glasgow Coma Scale ( GCS ) scores and the appearance of the admission computerized tomography scan . Intracranial pressure ( ICP ) was monitored in all patients from the surface subarachnoid space . Outcome at 6 months was assessed using the Glasgow Outcome Scale . Steroid and placebo groups were similar in terms of admission GCS score , intracranial pathology , incidence of associated injuries , and time interval from injury to admission to intensive care . The ICP generally increased during the first 48 hours of intensive therapy ; there was no difference in this trend between the steroid and placebo groups . A poorer outcome was observed in patients with elevated ICP who received steroids . No increase in the incidence of pulmonary , gastrointestinal , or other extracranial complications was seen in the steroid group . The 6-month outcome did not differ between the steroid and placebo groups . No advantage of high-dose dexamethasone on ICP trends or clinical outcome in the treatment of severe head injury has emerged from this study In a prospect i ve r and omized double-blind multicenter trial , the efficacy and safety of a 51-hour ultra-high intravenous dexamethasone dosing regimen was investigated in patients with moderate and severe head injury . 300 patients between 15 and 55 years of age were r and omized to receive either placebo or dexamethasone : 500 mg intravenous infusion within 3 h after trauma initially , followed by 200 mg after 3 h , thereafter 8 times 200 mg at 6 hourly intervals , result ing in a total administered dose of 2,3 g in 51 hours . Primary end points for assessment of efficacy were : Modified Glasgow Coma Scale ( grading 3 - 16 ) on Day 5 , modified Glasgow Outcome Scale ( grading 1 - 6 ) 10 - 14 months after injury , and the time interval until consciousness improved above a level of modified GCS > or = 8 . Secondary endpoints were CT results and neurological and laboratory data . The two groups were well matched with respect to important prognostic variables , such as age , severity of trauma , and interval between trauma and application of the drug . 269 patients ( 89.7 % ) were available for final examination after 10 - 14 months . Results were surprisingly favourable in both groups : Lethality in the dexamethasone and placebo group was 14.3 and 15.4 % , respectively , and 61.7 and 57.4 % , respectively , achieved social and professional rehabilitation after 10 - 14 months ( outcome scale 6 ) . No statistical difference was seen between the dexamethasone and the placebo group in any of the primary end points of efficacy and safety ( incidence of upper gastrointestinal bleeding , infection , and thrombosis ) . ( ABSTRACT TRUNCATED AT 250 WORDS Summary Out of a total of 157 hospitalized head-injured children , twelve years of age and under , fifteen were considered to be severe , three of whom died within 72 hours of admission . Nine children with closed head injuries who were in coma for at least 24 hours ( did not open eyes , speak , or follow comm and s ) , with absent or impaired oculocephalic reflex , impaired pupil reactivity to light , and who were decerebrating for at least twelve hours , were studied . Five were given high dose dexamethasone therapy ( 1 mg/kg ) within six hours of injury , repeated at six hours , and then maintained at 1 mg/kg/day for eight days , and four either received none or were treated with a low dose regimen ( 0.25 mg/kg/day ) . In those receiving high dose therapy , intracranial pressure waves were noticeably less , peak intracranial pressure was lower , and intensive care and hospital stay were shorter . It was also noted that in the high dose therapy group spontaneous eye opening and speech returned sooner , and all were considered to have returned to their premorbid status by six months following injury . Of the no steroid or low dose group , one died , and of the remainder at six months one was aphasic and still decerebrating , another was aphasic and severely h and icapped , and the third returned to school seven months after injury The present studies were conducted to test whether the outcome of severe head injury is improved by early administration of the synthetic corticosteroid triamcinolone . In a prospect i ve , double-blind , multicenter clinical trial , 396 patients with severe head injury were r and omized to a steroid group ( n=187 ) receiving 200 mg triamcinolone acetonide ( Volon A soluble ) i.v . within 4 h after trauma , followed by 3 × 40 mg/day i.v . for 4 days , and 3 × 20 mg/day i.v . for a further 4 days , and a placebo group ( n=209 ) receiving injections which did not contain any active drug . The placebo group was subjected to the same st and ard treatment procedures . Clinical features were not different between the groups upon admission to hospital . Subdural hematoma , epidural hematoma , and focal supratentorial contusion were among the most frequent diagnoses . The result of treatment with triamcinolone was assessed at discharge from the hospital and at 1 year after trauma . using the Glasgow Outcome Scale . Differences in favor of steroid treatment could be detected with regard to the patients ' condition at discharge ( P=0.0634 ) . More patients with steroids had a good recovery ( 49.2 % vs 40.7 % ) , and fewer died ( 16.0 % vs 21.5 % ) . Differences in outcome were even more pronounced ( P<0.0145 ) in patients with a focal lesion and a Glasgow Coma Score on admission of < 8 ( n=93 ) . In this group , 34.8 % of the patients made a good recovery , as against 21.3 % of the placebo group ; mortality was also lower in the verum group ( 19.6 % vs 38.3 % ) . The results indicate that a major subgroup of patients with severe head injury benefits from early administration of triamcinolone . Efficacy of the treatment can be expected , in particular , in patients with a focal cerebral lesion and a Glasgow Coma Score of < 8 on admission . Administration of steroids beginning at the scene of an accident would therefore be beneficial in these cases A prospect i ve r and omised study was performed on 25 children aged 1.4 to 15.8 years with severe head injury ( Glasgow Coma Scale⪕7 ) to determine the clinical effectiveness and the impact on endogenous cortisol production of high-dose steroid therapy . Thirteen patients ( group 1 ) received dexamethasone 1 mg/kg/day during the first 3 days and 12 ( group 2 ) not . All patients were treated with a st and ardized regimen . Urinary free cortisol was measured by radioimmunoassay , and the clinical data were recorded at hourly intervals . Outcome was assessed 6 months later using the Glasgow Outcome Scale . We found a higher frequency of bacterial pneumonias in the dexamethasone-treated patients ( 7/13 versus 2/12 ) . Group 1 showed a suppression of endogenous cortisol production from day 1 to day 6 . In group 2 , menu free cortisol was up to 5-fold higher than under basal conditions . The results in group 2 showed taht the endogenous steroid production reacts adequately to the stress of severe head injury . It probably is sufficient to elicit maximum glucocorticoid effects . There was no other statistically significant difference in the clinical and laboratory data between the two groups . We conclude that dexamethasone in high doses suppresses endogenous cortisol production up to 6 days and may increase the risk of bacterial infection without affecting the outcome or the clinical and laboratory data In 1990 , the Second National Acute Spinal Cord Injury Study reported that high-dosage methylprednisolone improves neurologic recovery in spinal-injured humans . The study showed that patients who received the drug within 8 hr after injury improved , whereas those who received the drug later did not . The drug significantly increased recovery even in severely injured patients who were admitted with no motor or sensory function below the lesion , contradicting a long-held dogma that such patients would not recover . Some research ers , however , have question ed the stratification of the patient population , the use of summed neurologic change scores , and the absence of functional assessment s. The stratification by injury severity and treatment time was planned a priori and based on objective criteria . Detailed analyses revealed no differences between groups attributable to stratification or r and omization . While multivariate analyses of the summed neurologic scores were used , the conclusions were corroborated by other analytical approaches that did not rely on summed scores . For example , treatment with methylprednisolone more than doubled the probability that patients would convert from quadriplegia or paraplegia to quadriparesis or paraparesis , analgesia to hypalgesia , and anesthesia to hypesthesia . The treatment also significantly improved neurologic scores in lumbosacral segments , indicating that beneficial effects were not limited to segments close to the lesion site . The treatment did not significantly affect mortality or morbidity . The study strongly suggests that methylprednisolone has significant beneficial effects in human spinal cord injury , that these effects occur only when the drug is given within 8 hr , and that it helps even in patients with severe spinal cord injuries . These conclusions have important implication s for spinal cord injury care and research A prospect i ve double-blind study of the effects of dexamethasone administration on the outcome of patients with severe head injuries was performed . Patients were stratified for severity of neurological injury and were treated with placebo , low-dose dexamethasone ( 16 mg/day ) , or high-dose dexamethasone ( 96 mg/day ) for a period of 6 days . Outcome was evaluated at 6 months following injury . Of the 76 patients available for analysis , a good outcome was achieved in 37 % of placebo-treated patients , 44 % of low-dose-treated patients , and 29 % of high-dose-treated patients . These differences are not statistically significant . Similarly dexamethasone administration had no statistically significant effect on intracranial pressure patterns or serial neurological examinations during hospitalization . Gastrointestinal bleeding occurred in only one patient . Good outcome was associated with age under 10 years , lighter depth of coma on admission , and the preservation of brain-stem reflexes upon admission . A recalculation of data in previous clinical series purporting to show an improvement in outcome as a result of corticosteroid therapy shows no significant difference in outcome when steroid- and placebo-treated patients are compared . In our series , 90 % of all deaths were caused by recurrent intracranial hematomas , medical complications , or diffuse brain injuries with parenchymal hemorrhage and tissue disruption -- causes of death which can not be affected by corticosteroid therapy . The study suggests that dexamethasone in either high or low dosages has no significant effect on morbidity and mortality following severe head injury This is a prospect i ve r and omized study of the efficacy of steroid therapy in patients with severe head injury . One hundred patients were r and omized into two equal groups : the steroid group received 5 mg/kg/day of methylprednisolone , and the nonsteroid group received no drug . The groups were similar in their clinical features . All patients received a st and ardized therapeutic regimen . The patients were also classified as early responders or nonresponders to the overall treatment protocol without regard to steroid administration , on the basis of change in Glasgow Coma Scale score during the first 3 days of admission . There was no statistically significant difference in the outcome of the steroid and nonsteroid group at 6 months . Of the responders who were on steroids , 74 % had good outcomes or were disabled , compared with 56 % of the responders who did not receive steroids . In the nonresponder group , the patients on steroids were actually associated with a worse outcome than those who did not receive steroids : 75 % of the nonresponders who received steroids were dead or vegetative , compared to 56 % of those who were not receiving steroids . The data suggest that : 1 ) the effect of steroids may be different for different patient groups ; 2 ) in order to identify these patients , a sensitive coma scale is needed ; and 3 ) a rational approach to steroid therapy in head-injured patients may be to start all patients on steroids , but to discontinue their use in patients identified as not benefiting from steroid therapy MRC CRASH is a r and omised controlled trial ( IS RCT N74459797 ) of the effect of corticosteroids on death and disability after head injury . We r and omly allocated 10,008 adults with head injury and a Glasgow Coma Scale score of 14 or less , within 8 h of injury , to a 48-h infusion of corticosteroid ( methylprednisolone ) or placebo . Data at 6 months were obtained for 9673 ( 96.7 % ) patients . The risk of death was higher in the corticosteroid group than in the placebo group ( 1248 [ 25.7 % ] vs 1075 [ 22.3 % ] deaths ; relative risk 1.15 , 95 % CI 1.07 - 1.24 ; p=0.0001 ) , as was the risk of death or severe disability ( 1828 [ 38.1 % ] vs 1728 [ 36.3 % ] dead or severely disabled ; 1.05 , 0.99 - 1.10 ; p=0.079 ) . There was no evidence that the effect of corticosteroids differed by injury severity or time since injury . These results lend support to our earlier conclusion that corticosteroids should not be used routinely in the treatment of head injury Glucocorticoids are used in an attempt to reduce brain edema secondary to head injury . Nevertheless , their usefulness remains uncertain and contradictory . In a r and omized study of 24 children with severe head injury , urinary free cortisol was measured by radioimmunoassay . Twelve patients ( group 1 ) received dexamethasone and 12 ( group 2 ) did not . All patients were treated with a st and ardized regimen . In group 1 there was complete suppression of endogenous cortisol production . In group 2 free cortisol was up to 20-fold higher than under basal conditions and reached maximum values on days 1–3 . Since the excretion of cortisol in urine reflects the production rate closely and is not influenced by liver function and barbiturates , the results in group 2 show that the endogenous production of steroids is an adequate reaction to severe head injury . Exogenous glucocorticoids are thus unlikely to have any more beneficial effects than endogenous cortisol BACKGROUND Corticosteroids have been used to treat head injuries for more than 30 years . In 1997 , findings of a systematic review suggested that these drugs reduce risk of death by 1 - 2 % . The CRASH trial -- a multicentre international collaboration-- aim ed to confirm or refute such an effect by recruiting 20000 patients . In May , 2004 , the data monitoring committee disclosed the unmasked results to the steering committee , which stopped recruitment . METHODS 10008 adults with head injury and a Glasgow coma score ( GCS ) of 14 or less within 8 h of injury were r and omly allocated 48 h infusion of corticosteroids ( methylprednisolone ) or placebo . Primary outcomes were death within 2 weeks of injury and death or disability at 6 months . Prespecified subgroup analyses were based on injury severity ( GCS ) at r and omisation and on time from injury to r and omisation . Analysis was by intention to treat . Effects on outcomes within 2 weeks of r and omisation are presented in this report . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N74459797 . FINDINGS Compared with placebo , the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids ( 1052 [ 21.1 % ] vs 893 [ 17.9 % ] deaths ; relative risk 1.18 [ 95 % CI 1.09 - 1.27 ] ; p=0.0001 ) . The relative increase in deaths due to corticosteroids did not differ by injury severity ( p=0.22 ) or time since injury ( p=0.05 ) . INTERPRETATION Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury . The cause of the rise in risk of death within 2 weeks is unclear A prospect i ve double-blind clinical trial was performed on 161 patients to determine the effectiveness of high-dose steroid therapy in patients admitted comatose after a non-missile-related head injury . Patients were r and omized into a high-dose dexamethasone phosphate group and a placebo group . The initial dose of 100 mg of dexamethasone was administered within 6 hours of the accident . For statistical analysis , a sequential test was chosen , using survival at 1 month as a basic criterion of effectiveness . No significant difference was found in the 1-month survival rate or in the distribution of outcome after 6 months , either within the group as a whole , or in subgroups with varying severity of brain damage on admission . The authors conclude that dexamethasone in high doses has no statistically significant effect on morbidity or mortality in head-injured patients who are comatose on admission |
2,208 | 31,485,187 | The drug class effect of SUA reduction suggesting SGLT2 inhibitors might be beneficial for diabetic patients with hyperuricemia | To describe the effects of sodium-glucose co-transporter 2 ( SGLT2 ) inhibitors on serum uric acid ( SUA ) in patients with type 2 diabetes mellitus ( T2DM ) . | AIMS Dapagliflozin , a highly selective inhibitor of sodium-glucose cotransporter 2 ( SGLT2 ) , reduces hyperglycaemia and weight in patients with type 2 diabetes mellitus ( T2DM ) by increasing urinary glucose excretion . Long-term glycaemic control , body composition and bone safety were evaluated in patients with T2DM after 102 weeks of dapagliflozin treatment . METHODS This r and omized , double-blind , placebo-controlled study ( NCT00855166 ) enrolled patients with T2DM [ mean : age 60.7 years ; HbA1c 7.2 % ; body mass index ( BMI ) 31.9 kg/m(2 ) ; body weight 91.5 kg ] inadequately controlled on metformin . Patients ( N = 182 ) were r and omly assigned 1 : 1 to receive dapagliflozin 10 mg/day or placebo added to open-label metformin for a 24-week double-blind treatment period followed by a 78-week site- and patient-blinded extension period . At week 102 , changes from baseline in HbA1c , weight , waist circumference , total body fat mass as measured by dual-energy X-ray absorptiometry ( DXA ) , serum markers of bone turnover , bone mineral density ( BMD ) as measured by DXA , and adverse events were evaluated . RESULTS A total of 140 patients ( 76.9 % ) completed the study . Over 102 weeks , dapagliflozin-treated patients showed reductions in HbA1c by -0.3 % , weight by -4.54 kg , waist circumference by -5.0 cm and fat mass by -2.80 kg without increase in rate of hypoglycaemia . Compared with placebo , no meaningful changes from baseline in markers of bone turnover or BMD were identified over 102 weeks . One fracture occurred in each treatment group . The frequency of urinary tract infection ( UTI ) and genital infection was similar in both treatment groups . CONCLUSIONS Over 102 weeks , dapagliflozin improved glycaemic control , and reduced weight and fat mass , without affecting markers of bone turnover or BMD in patients with T2DM inadequately controlled on metformin OBJECTIVE To determine whether dapagliflozin , which selectively inhibits renal glucose reabsorption , lowers hyperglycemia in patients with type 2 diabetes that is poorly controlled with high insulin doses plus oral antidiabetic agents ( OADs ) . RESEARCH DESIGN AND METHODS This was a r and omized , double-blind , three-arm parallel-group , placebo-controlled , 26-center trial ( U.S. and Canada ) . Based on data from an insulin dose-adjustment setting cohort ( n = 4 ) , patients in the treatment cohort ( n = 71 ) were r and omly assigned 1:1:1 to placebo , 10 mg dapagliflozin , or 20 mg dapagliflozin , plus OAD(s ) and 50 % of their daily insulin dose . The primary outcome was change from baseline in A1C at week 12 ( dapagliflozin vs. placebo , last observation carried forward [ LOCF ] ) . RESULTS At week 12 ( LOCF ) , the 10- and 20-mg dapagliflozin groups demonstrated −0.70 and −0.78 % mean differences in A1C change from baseline versus placebo . In both dapagliflozin groups , 65.2 % of patients achieved a decrease from baseline in A1C ≥0.5 % versus 15.8 % in the placebo group . Mean changes from baseline in fasting plasma glucose ( FPG ) were + 17.8 , + 2.4 , and −9.6 mg/dl ( placebo , 10 mg dapagliflozin , and 20 mg dapagliflozin , respectively ) . Postpr and ial glucose ( PPG ) reductions with dapagliflozin also showed dose dependence . Mean changes in total body weight were −1.9 , −4.5 , and −4.3 kg ( placebo , 10 mg dapagliflozin , and 20 mg dapagliflozin ) . Overall , adverse events were balanced across all groups , although more genital infections occurred in the 20-mg dapagliflozin group than in the placebo group . CONCLUSIONS In patients receiving high insulin doses plus insulin sensitizers who had their baseline insulin reduced by 50 % , dapagliflozin decreased A1C , produced better FPG and PPG levels , and lowered weight more than placebo Sodium – glucose cotransporter 2 ( SGLT2 ) inhibitors are a newly approved class of glucose-lowering medications with a novel mechanism of action . These agents increase glycosuria , which leads to improved glucose control . They also produce an osmotic diuresis that , in part , contributes to blood pressure reduction and calorie loss secondary to glycosuria leading to weight loss ( 1,2 ) . A recent review of SGLT2 inhibitors focuses on the blood pressure – lowering effects of the two approved glucose-lowering agents , dapagliflozin and canagliflozin ( 3 ) . While not approved as antihypertensive agents , they may potentially aid in lowering blood pressure in patients with diabetes . A review of studies in both hypertensive and normotensive patients with type 2 diabetes demonstrates a 4–10 mmHg reduction of systolic blood pressure ( 3 ) . In this issue of Diabetes Care , Tikkanen et al. ( 4 ) investigate the effectiveness and safety of the newest agent in this class , empagliflozin , on blood pressure using 24-h ambulatory blood pressure monitoring . This study r and omized over 800 subjects with type 2 diabetes , mean age of 60 years , and good kidney function ( i.e. , a mean estimated glomerular filtration rate [ eGFR ] of 84 mL/min/1.73 m2 ) . These subjects either were normotensive ( < 140/90 mmHg ) or had stage 1 hypertension ( ≥140/90 < 160/99 mmHg ) . They were r and omized to either empagliflozin 10 mg daily , empagliflozin 25 mg Uric acid is associated with cardiovascular disease and cardiovascular disease risk factors in adults , including chronic kidney disease , coronary artery disease , stroke , diabetes mellitus , preeclampsia , and hypertension . We examined the association between uric acid and elevated blood pressure in a large , nationally representative cohort of US adolescents , a population with a relatively low prevalence of cardiovascular disease and cardiovascular disease risk factors . Among 6036 adolescents 12 to 17 years of age examined in the 1999–2006 National Health and Nutrition Examination Survey , the mean age was 14.5 years , 17 % were obese ( body mass index : ≥95th percentile ) , and 3.3 % had elevated blood pressure . Mean serum uric acid level was 5.0 mg/dL , and 34 % had a uric acid level ≥5.5 mg/dL. In analyses adjusted for age , sex , race/ethnicity , and body mass index percentile , the odds ratio of elevated blood pressure , defined as a systolic or diastolic blood pressure ≥95th percentile for age , sex , and height , for each 0.1-mg/dL increase in uric acid level was 1.38 ( 95 % CI : 1.16–1.65 ) . Compared with < 5.5 mg/dL , participants with a uric acid level ≥5.5 mg/dL had a 2.03 times higher odds of having elevated blood pressure ( 95 % CI : 1.38–3.00 ) . In conclusion , increasing levels of serum uric acid are associated with elevated blood pressure in healthy US adolescents . Additional prospect i ve studies and clinical trials are needed to determine whether uric acid is merely a marker in a complex metabolic pathway or causal of hypertension and , thus , a potential screening and therapeutic target |
2,209 | 23,904,209 | MAIN RESULTS No differences were found in contraceptive effectiveness for the 13 COC pairs for which this outcome was reported .
Compared to the higher-estrogen pills , several COCs containing 20 μg EE result ed in higher rates of early trial discontinuation ( overall and due to adverse events such as irregular bleeding ) as well as increased risk of bleeding disturbances ( both amenorrhea or infrequent bleeding and irregular , prolonged , frequent bleeding , or breakthrough bleeding or spotting ) .
Low-dose estrogen COCs result ed in higher rates of bleeding pattern disruptions . | BACKGROUND Concern about estrogen-related adverse effects has led to progressive reductions in the estrogen dose in combination oral contraceptives ( COCs ) .
However , reducing the amount of estrogen to improve safety could result in decreased contraceptive effectiveness and unacceptable changes in bleeding patterns .
OBJECTIVES To test the hypothesis that COCs containing ≤ 20 μg ethinyl estradiol ( EE ) perform similarly as those containing > 20 μg in terms of contraceptive effectiveness , bleeding patterns , discontinuation , and side effects . | BACKGROUND Many women discontinue their use of hormonal contraception , and even those who continue so may have difficulty using oral contraceptive pills consistently . New delivery systems , including the vaginal ring , may be easier to use , but user acceptability and satisfaction with these new methods may be affected by women 's experience with their bodies . MATERIAL S AND METHODS Data for this study were collected as part of a r and omized clinical trial on 201 women comparing immediate start of vaginal ring use with immediate start of low-dose oral contraceptive use . We assessed user satisfaction and method continuation 3 months after ring or pill initiation . RESULTS At 3 months , 174 of 201 subjects ( 87 % ) had follow-up interviews . Among the 174 study participants with follow-up data , 61 % of ring subjects and 34 % of pill subjects were very satisfied with their methods ( p=.003 ) . For posttrial contraception , 79 % of ring subjects chose to continue with the ring whereas 59 % of pill subjects chose to continue with the pill ( p<.001 ) . Women who reported greater comfort in touching their genitals , greater frequency of masturbation , more comfort with intercourse and past use of vaginal contraceptives and products were not more likely than others to be satisfied with the ring or to continue using it for birth control . CONCLUSION Women who were allocated to vaginal ring use , regardless of their baseline characteristics or behavior , were likely to be highly satisfied with the method and to continue its use This was an open-label multicenter study to compare the cycle control and effect on well-being of two oral contraceptives containing gestodene and one containing desogestrel . A total of 2419 healthy women ≤ 41 years of age were r and omized to receive oral contraceptives containing monophasic gestodene ( Minulet ® ; n = 806 , mean age 24.5 years ) , triphasic gestodene ( Tri-Minulet ® ; n = 808 , mean age 24.6 years ) or monophasic desogestrel ( Mercilon ® ; n = 805 , mean age 24.6 years ) . Subjects were to participate in the study for up to 13 treatment cycles . A modified Moos Menstrual Distress Question naire was used to evaluate menstrual symptoms and to assess overall well-being . A total of 698 women were withdrawn from the study , 154 due to adverse events . Cycle control with gestodene was superior to that with desogestrel at almost all time points , particularly for breakthrough bleeding and /or spotting , which occurred significantly less frequently with gestodene than with desogestrel at cycles 1–1 and 9–11 ( p < 0.05 ) . Generally , the proportion of subjects with breakthrough bleeding and /or spotting was almost twice as great with desogestrel as with gestodene . The duration of bleeding was not consistently different between the gestodene and desogestrel groups ; however , the intensity of bleeding was greater with gestodene at all time points ( p < 0.05 ) . The latent period before withdrawal bleeding was significantly longer for monophasic gestodene at cycles 1–5 and 8–10 ( p < 0.05 ) . Treatment significantly improved overall well-being at cycles 6 and 9 with triphasic gestodene and at cycle 13 with desogestrel ; however , no statistically significant differences among treatment groups in overall well-being scores or individual factors of well-being could be identified . All three treatments were well tolerated . The most common drug-related adverse events were headache ( 14.2 % ) , breast pain ( 6.2 % ) , nausea ( 4.1 % ) , metrorrhagia ( 5.9 % ) and abdominal pain ( 3.5 % ) . The incidence of adverse events in all treatment groups was similar , with the exception of metrorrhagia , which occurred in more patients in the desogestrel group than in the gestodene treatment groups ( p < 0.05 ) The early days of oral contraceptives showed some evidence that these medications may have caused undesirable side effects on the voice , mainly in terms of virilization . In a r and om study carried out at the university hospitals of Jena and Berlin ( Charité ) , two more recent drugs were tested in this regard , one containing cyproterone acetate ( Diane-35 ) and the other one levonorgestrel ( Microgynon ) , both from Schering . Ninety-one patients took part in extensive clinical and instrumental phoniatric investigations of voice function over a period of one year . No significant side effects on the voice could be proven for the two preparations . Gynecological and clinical effects of both Diane-35 and Microgynon were similar during the one-year study period . Women taking Diane-35 had less intracyclic bleedings and amenorrhea . Also , acne was more favorably influenced by Diane-35 The aim of this study was to compare contraceptive reliability , cycle control , and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol ( EE2 ) and 75 micrograms gestodene ( GSD ) , with a reference preparation containing a similar dose of gestodene but in combination with 30 micrograms ethinylestradiol . A higher incidence of intermenstrual bleeding was apparent under the 20 micrograms EE2 oral contraceptive . For the 20 micrograms EE2 preparation , 47.4 % of all women reported spotting at least once over a period of 12 treatment cycles , whereas this figure was 35.5 % for the 30 micrograms EE2 pill ( p < 0.05 ) . However , the incidence was within a range that corresponds to that of other OCs . The cumulative breakthrough bleeding rates ( at least once during the one year of treatment ) of 14.5 % ( 20 micrograms EE2 ) and 11.8 % ( 30 micrograms EE2 ) of women were not significantly different . In relation to all cycles , the intermenstrual bleeding rates were remarkably lower , indicating that the majority of the volunteers experienced such events only in few cycles under treatment : the spotting rate was 11.5 % ( 20 micrograms EE2 ) and 7.2 % ( 30 micrograms EE2 ) of all cycles , and the breakthrough bleeding rate was 2.6 % and 1.6 % of all cycles , respectively . Three pregnancies were recorded during the study ( one in the 20 micrograms EE2 + 75 micrograms GSD group , two in the 30 micrograms EE2 + 75 micrograms GSD group ) . All three could be explained either by intake irregularities or by circumstances impairing the contraceptive effect . The influence of both treatments on the blood pressure and body weight proved to be extremely slight . Adverse events in both groups were rare and differences in the frequency of adverse events were not apparent . The discontinuation rate due to adverse events , including intermenstrual bleeding , was low ( 9.8 % for 20 micrograms EE2 + 75 micrograms GSD , and 7.2 % for 30 micrograms EE2 + 75 micrograms GSD ) and was in the lower range known for other oral contraceptives . Both preparations were well accepted by the volunteers . The data obtained demonstrate clinical ly acceptable cycle control , good tolerance , and a high st and ard of contraceptive reliability for both drugs . Prescription of the 20 micrograms EE2 preparation could be the first-line therapy in order to provide the lowest amount of EE2 possible . In case of persistent cycle control problems , a switch to the 30 micrograms EE2 drug should be considered BACKGROUND The aim of this prospect i ve study was to evaluate the changes in olfactory sensitivity of oral contraceptive ( pill ) users . METHODS Sixty women underwent rhinomanometric and olfactometric determinations during the follicular , periovular and luteal phases of the menstrual cycle , and at day 7 , 14 and 21 of contraceptive intake . Thirty-one women used 30 microg ethinyl oestradiol plus 75 microg gestodene and 29 women used 20 microg ethinyl oestradiol plus 150 microg desogestrel . RESULTS Rhinomanometry showed higher but not statistically significant values during the periovular phase than in the follicular and luteal phases . Olfactometry showed a higher sensitivity during the follicular and periovular phases than during the luteal phase of the menstrual cycle . The rhinomanometric surveys in pill users were statistically different from those of the luteal phase ( P < 0.02 ) and the follicular and periovular phases ( P < 0.001 ) . The olfactometric thresholds during the period of contraceptive use were statistically different from those of the follicular phase for a few odorous substances , and from those of the periovular phase for each odorous substance , but similar to those of the luteal phase ( P = NS ) . CONCLUSIONS Unlike the rhinomanometric airflow and trans-nasal pressure , the olfactory threshold to odours seems to depend on the variations of the ovarian steroids during the menstrual cycle and on the iatrogenic effects of oral contraceptives OBJECTIVE -- To describe the technique of hysterosalpingography with endocervical placement of the balloon of the catheter rather than endometrial placement . PATIENTS -- 48 consecutive patients undergoing hysterosalpingography in the course of infertility work-up at a university hospital . METHOD -- With the patient in the lithotomy position , the cervix is visualized and cleansed . The catheter and balloon are inserted in the cervical canal and inflated with the contrast agent . The contrast agent is injected slowly at low pressure , and three to six spot films are obtained . Only gentle traction can be applied by this method , so oblique views are obtained early in the examination . RESULTS -- Balloon placement was atraumatic . Although good views were obtained more frequently than with traditional techniques , about one-quarter of the studies were unsatisfactory . CONCLUSION -- This method is easy , atraumatic , and allows excellent visualization of the entire endometrial cavity and upper intracervical canal A r and omised cross-over trial was performed to compare the pharmacodynamic actions of three low-dose oral contraceptives ( OCs ) : Marvelon ( 150 micrograms desogestrel (DSG)+ 30 micrograms ethinyloestradiol ( EE ) ) , Mercilon ( 150 micrograms DSG + 20 micrograms EE ) and Microgynon ( 150 micrograms levonorgestrel ( LNG ) + 30 micrograms EE ) . None of the OCs produced any significant changes in serum cholesterol , LDL-C and apoprotein B. Triglycerides were increased by the desogestrel OCs but not by Microgynon . The latter however increased the glucose and insulin responses to a glucose tolerance test whereas Marvelon and Mercilon had no effect . HDL-C increased with Marvelon , was unchanged with Mercilon and was decreased with Microgynon . Apoprotein AII was increased by all three OCs but only the DSG OCs increased apoprotein AI . All OCs produced similar increases in caeruloplasmin but the increase in SHBG was much greater with Marvelon and Mercilon than with Microgynon . Testosterone was reduced more with Microgynon than with the DSG OCs . Many of the changes reflect the strong anti-oestrogenic action of LNG on metabolic parameters compared to DSG . Except for the effect on HDL-C , there was little difference between Marvelon and Mercilon on metabolic parameters and this complements the findings from large-scale clinical trials of the two OCs . Mercilon , therefore provides a very satisfactory alternative to Marvelon OBJECTIVES Our purpose was to define the frequency and reasons for oral contraceptive discontinuation and subsequent contraceptive behavior . STUDY DESIGN A nationwide prospect i ve study of 1657 women initiating or switching to the use of a new contraceptive from private practice s , clinics , and a health maintenance organization was performed . RESULTS Six months after a new oral contraceptive prescription , 68 % of new starts and 84 % of switchers still used oral contraceptives . Of women who discontinued , 46 % did so because of side effects , whereas 23 % had no continuing need . More than four fifths of women who discontinued oral contraceptives but remained at risk of unintended pregnancy either failed to adopt another method or adopted a less effective method . Fifteen percent of women who discontinued oral contraceptives resumed their use within the 7-month follow-up period . CONCLUSIONS Counseling should emphasize the possibility of side effects , stressing the fact that most will be transient , and the need to identify a backup method . Follow-up visits should be scheduled for 1 to 2 months after a prescription is written In a double-blind , controlled , r and omized , four-arm , bicentric clinical study , the effect of four oral contraceptives ( OCs ) on thyroid hormone parameters , cortisol , aldosterone , endothelin-1 and angiotensin II was investigated . Four groups composed of 25 volunteers each ( ages between 18 and 35 years ) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol ( EE ) + 2 mg dienogest ( DNG ) ( 30EE/DNG ) , 20 microg EE + 2 mg DNG ( 20EE/DNG ) , 10 microg EE + 2 mg estradiol valerate ( EV ) + 2 mg DNG ( EE/EV/DNG ) or 20 microg EE + 100 microg levonorgestrel ( LNG ) ( EE/LNG ) . The study was completed by 91 subjects . Blood sample s were taken by venipuncture after at least 12 h fasting on Day 21 - 26 of the control cycle and on Day 18 - 21 of the first , third and sixth treatment cycle . There was a significant increase in triiodothyronine ( T3 ) and thyroxine ( T4 ) by 20 - 40 % in all treatment cycles , while thyroid-stimulating hormone was significantly increased only with EE/EV/DNG . Treatment with the DNG-containing OCs caused no change in free T4 ( FT4 ) and a transitory reduction in free T3 ( FT3 ) levels during the first cycle . During intake of EE/LNG , FT4 rose slightly , while FT3 was not altered . The pronounced rise in the serum concentrations of cortisol appeared to be related to the EE dose . During the first three cycles of treatment , no effect on angiotensin II levels was observed , while in the sixth cycle a significant decrease was measured in all treatment groups . The four OCs did not influence the serum concentrations of endothelin-1 and no consistent effects were found concerning those of aldosterone . The results suggest that the three DNG-containing and the LNG-containing low-dose OCs may increase T3 , T4 and cortisol due to an elevated binding to serum globulins , while the free proportion of the hormones is not or only slightly changed . Therefore , these OCs have only minor effects on thyroid function , adrenal and blood pressure serum parameters In a 6-month , r and omized , double-blind study the effects of two combined oral contraceptives containing 150 micrograms desogestrel and either 20 or 30 micrograms ethinylestradiol on hemostatic parameters were investigated in 1633 healthy women . Compared with baseline , the 30 micrograms ethinylestradiol formulation increased prothrombin fragment 1 + 2 ( + 72.2 % ) , D-dimer ( + 42.4 % ) and protein C activity ( + 6.1 % ) , whereas antithrombin-III activity ( -6.3 % ) and protein S activity ( -19.7 % ) were decreased . The use of the 20 micrograms ethinylestradiol formulation was associated with the same pattern of changes , but with lower magnitude ( F1 + 2 + 61.1 % , D-dimer + 36.0 % , antithrombin III -5.3 % , protein C + 4.6 % and protein S-16.0 % ) . The changes from baseline were significantly smaller in the 20 micrograms ethinylestradiol group for D-dimer , antithrombin III and protein S than in the 30 micrograms ethinylestradiol group ( p = 0.019 , p = 0.038 and p = 0.001 , respectively ) . One woman with a combined deficiency of proteins C and S developed deep venous thrombosis while using the 20 micrograms ethinylestradiol formulation . Use of both formulations was associated with a shift of the coagulation-fibrinolysis balance to an enhanced fibrin-generating and fibrin-degradating activity . The less-pronounced effect on hemostasis with the 20 micrograms ethinylestradiol preparation is reassuring with regard to thromboembolic risk in general . However , women with coagulation inhibitor deficiency should be advised not to use oral contraceptives Abstract . Ninety‐eight women seeking contraceptive advice were r and omly allocated to 6 months of treatment with one of the following four combinations of ethinylestradiol ( EE ) and levonorgestrel ( NG ) : 20/250 , 30/250 , 30/150 , and the so‐called triphasic drug . The EE/NG ratios were 0.08 , 0.12 , 0.20 and 0.36 respectively . Blood lipids , HDL‐cholesterol and sex hormone binding globulin ( SHBG ) were determined twice before treatment and after 1 , 3 and 6 months of medication PURPOSE In this open-label , r and omized study , we assessed the effects on hemostasis of two combined oral contraceptives containing drospirenone ( DRSP ) as progestogen component . METHODS Three milligrams of DRSP , a progestogen with antimineralocorticoid activity , was combined with either 30 or 20 microg ethinyl estradiol ( EE ) ( DRSP/30EE ; DRSP/20EE ) and compared with a preparation containing 150 microg desogestrel ( DSG ) and 30 microg ethinyl estradiol ( DSG/30EE ) . A total of 75 healthy female volunteers aged 18 - 35 years were enrolled . The hemostasis variables were measured in the medication-free precycle ( baseline ) ; in the first , third and sixth treatment cycle ; and in the follow-up phase . The target variables for comparison were the relative changes from baseline to Cycle 6 . RESULTS Data of 25 volunteers in each group were valid for the per- protocol evaluation . Most changes in hemostasis variables were similar in the three treatment groups . All procoagulatory variables and the anticoagulatory variable protein C antigen increased slightly , while protein S antigen and activity decreased . For fibrinogen and protein S activity , the changes were statistically significant : less pronounced with DRSP/20EE compared to DSG/30EE at Cycle 6 . There were no statistically significant differences in the changes of antifibrinolytic variables , the global clotting tests and D-dimer . All pairwise comparisons of DRSP/30EE vs. DSG/30EE yielded nonsignificant results ; however , there was a trend of a lower impact of DRSP/20EE on nearly all hemostatic parameters compared to the 30EE products . All three study treatments were safe and well tolerated by the volunteers and provided adequate contraceptive reliability . CONCLUSION The changes in the hemostatic variables for DRSP/20EE were less pronounced compared to DSG/30EE and DRSP/30EE . The results were in accordance with previous reports on effects of similar OCs The aim of the study was to evaluate if a pill containing the same dose of the same type of progestin compound ( gestodene , GES , 75 microg ) but different doses of ethinylestradiol ( EE2 ) ( 20 or 30 microg ) differently influences specific markers of bone resorption ( urinary levels of pyridinoline ( PYR ) and dexoxypyridinoline ( D-PYR ) ) . During the 12 months of the study a significant decrease of urinary levels of PYR and D-PYR was found in 2 groups of young post-adolescent women taking the pills with 20 and 30 microg of EE2 in comparison with control women ( subjects of the same age group with normal menstrual cycle who did not use contraception ) . In women taking pills with 20 or 30 microg EE2 , the levels of sex hormone-binding globulin ( SHBG ) significantly increased during treatment in comparison with baseline , whereas in the same time period no changes occurred in control women . These findings suggest that similar to the pill containing 30 microg EE2 , the lower dosage of the EE2 pill ( 20 microg ) is also capable of reducing bone resorption . Twenty and 30 microg EE2 pills exert the same biological estrogenic effect . In fact , SHBG levels significantly increased with both pills . However , an additional effect of the progestin compound that could act directly on progestin or estrogen receptors of bone can not be excluded . Since contraception with a pill containing the lowest estrogen dose is associated with the lowest incidence of side effects , these findings further suggest a pill containing 20 microg EE2 for young post-adolescent women would be the best choice The aim of the present study was to compare changes in the endogenous and rogen environment in healthy women while on low-dose oral contraceptives ( OCs ) . One-hundred healthy women were r and omized to receive one of four OCs during six months : 21 tablets of Cilest , Femodeen , Marvelon , or Mercilon . During the luteal phase of the pretreatment cycle , body weight and blood pressure were recorded and the following parameters were measured : sex hormone-binding globulin ( SHBG ) , corticosteroid-binding globulin ( CBG ) , testosterone ( T ) , free testosterone ( FT ) , 5 alpha-dihydrotestosterone ( DHT ) , and rostenedione ( A ) , dehydroepi and rosterone-sulphate ( DHEA-S ) and 17 alpha-hydroxyprogesterone ( 170HP ) while also the free and rogen index ( FAI ) was calculated . Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month . There were no differences on body mass and blood pressure with the use of the four OCs . The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon group when compared to Cilest and Marvelon ( approximately 20 % vs 45 % ) . Mean serum SHBG and CBG increased significantly in all four groups approximately 250 % and 100 % , respectively . In each group CBG also increased significantly but less in women taking Mercilon ( -75 % ) as compared to the others ( -100 % ) . Current low-dose OCs were found to have similar impact on the endogenous and rogen metabolism with significant decreases of serum testosterone , DHT , A , and DHEA-S. They may be equally beneficial in women with and rogen related syndromes such as acne and hirsutism OBJECTIVES To compare the bleeding patterns and cycle control of an oral contraceptive ( OC ) containing ethinylestradiol ( EE ) 30 μg/drospirenone ( drsp ) 3 mg administered in a 21/7 regimen versus a lower-dose OC containing EE 20 μg/drsp 3 mg administered in a 24/4 regimen , using data from two identically design ed studies . MATERIAL S AND METHODS In the first study , 326 healthy women ( 18 - 35 years ) received EE 30 μg/drsp 3 mg in a 21/7 regimen . In the second study , 1027 healthy women ( 17 - 36 years ) received EE 20 μg/drsp 3 mg in a 24/4 regimen . Participants recorded bleeding using daily completed diaries over 13 treatment cycles . RESULTS During cycles 1 - 12 , the prevalence of scheduled withdrawal bleeding was lower with EE 20 μg/drsp 3 mg 24/4 than with EE 30 μg/drsp 3 mg 21/7 ( 82.0 - 91.7 % versus 94.8 - 100.0 % of women , respectively ) ; moreover , a higher proportion of women reported a maximum intensity of light scheduled withdrawal bleeding with EE 20 μg/drsp 3 mg 24/4 than with EE 30 μg/drsp 3 mg 21/7 ( 30.9 - 39.0 % versus 13.8 - 20.5 % of women , respectively ) . In cycles 2 - 13 , unscheduled intracyclic bleeding was reported by 7.7 - 13.8 % of EE 20 μg/drsp 3 mg 24/4 recipients and 3.8 - 7.9 % of EE 30 μg/drsp 3 mg 21/7 recipients ; these were mainly single bleeding days . During reference periods 1 - 4 , the mean number of bleeding episodes was similar between groups ( 3.1 - 3.3 episodes with EE 20 μg/drsp 3 mg 24/4 versus 3.2 episodes with EE 30 μg/drsp 3 mg 21/7 ) . CONCLUSIONS A low-dose 24/4 regimen OC containing EE 20 μg/drsp 3 mg is generally comparable in terms of bleeding to a higher-dose 21/7 regimen OC containing EE30 μg/drsp 3 mg . Between-treatment differences in bleeding intensity and unscheduled intracyclic bleeding rates were observed OBJECTIVE To reassess and compare cycle control attained with two combined hormonal contraceptives , norgestimate (NGM)/ethinyl estradiol ( EE ) 25 microg and norethindrone acetate (NETA)/EE 20 microg , by new general criteria recommendations for all combined hormonal contraceptives . DESIGN Analysis of bleeding data for cycles 1 - 6 from a r and omized , multicenter trial . SETTING 221 North American centers . PATIENT(S ) Healthy , sexually active women ( 18 - 45 years old ) . INTERVENTION(S ) NETA/EE : 1 mg NETA/20 microg EE , days 1 - 21 of each cycle and 75 mg of ferrous fumarate , days 22 - 28 ; NGM/EE : triphasic NGM in 7-day increments ( days 1 - 7 : 180 microg ; days 8 - 14 : 215 microg ; days 15 - 21 : 250 microg ) and 25 microg EE , placebo on days 22 - 28 . MAIN OUTCOME MEASURE(S ) Cycle control evaluated from patients ' daily diaries . RESULT ( S ) For cycles 1 - 6 , there was a statistically significant lower incidence of unscheduled bleeding/spotting with NGM/EE 25 microg ( range 21.0%-34.4 % ) than with NETA/EE 20 microg ( range 33.0%-46.6 % ) . Of the women who had unscheduled bleeding/spotting , the mean number of days per cycle of bleeding/spotting was comparable . A statistically significant higher incidence of scheduled bleeding was seen with NGM/EE 25 microg ( 95.2%-97.5 % ) than with NETA/EE 20 microg ( 78.5%-84.2 % ) . CONCLUSION ( S ) The NGM/EE 25 microg has a lower incidence and comparable length of unscheduled bleeding and a higher incidence of scheduled bleeding than NETA/EE 20 microg in this post hoc analysis The aim of this study was to assess whether during regular OC use ovarian activity might lead to ovulation , as assessed by ultrasound ( US ) evaluation of follicular growth and blood levels of 17-beta-estradiol and progesterone . A total of 51 healthy women with normal menstrual cycles ( 28 + /- 3 days ) and no gynecological symptoms were recruited . A total of 22 patients were given a triphasic OC pill containing 35 mg ethinyl estradiol ( EE ) and 50 mg desogestrel ( DSG ) in the first seven tablets ; 30 mg EE and 100 mg DSG in tablets 8 to 14 , and 30 mg EE and 150 mg DSG in tablets 15 to 21 ; 29 patients received one of two OC pills , both containing 20 mg EE plus 150 mg DSG ( 15 patients ) or 75 mg of gestodene ( 14 patients ) . A total of 86 cycles were monitored : 51 during the 3rd-4th cycle and 35 during the 6th-8th cycle of OC treatment . Follicular-like structures were observed in nine patients . The frequency of follicular-like structures was similar during the 3rd-4th cycle ( 9 % ) and during the 6th-8th cycle ( 11 % ) . There was no relationship between follicular growth and blood levels of E2 and progesterone , which always appeared suppressed . In conclusion , the results of this study suggest that during OC use ( even with low dose of ethinyl estradiol ) , a little ovarian activity may be present without ovulation OBJECTIVE To compare a traditional 28‐day cycle to an extended 49‐day cycle of the 30 μg ethinyl estradiol (E2)/300 μg norgestrel monophasic birth control pill regimen . METHODS Ninety subjects r and omized to either 28‐day cycles with 21 active pills or 49‐day cycles with 42 active pills for a prospect i ve open label trial over four 84‐day reference periods or trimesters . Bleeding , pill taking , and symptom diaries were completed . The sample size with 80 % power to detect a 40 % reduction in bleeding days required 24 subjects in each arm . RESULTS Of the 90 women , 24 subjects ( 54.5 % ) on the 28‐day cycle and 29 ( 63 % ) on the 49‐day cycle completed the entire study ( P = .41 ) . There were no statistically significant differences between the two groups in demographics or continuation rates . There was a significant reduction in bleeding days in the experimental arm beginning in the first trimester ( 28‐day = 10.9 , 49‐day = 6.4 mean days of bleeding , P < .001 ) and continuing to the fourth trimester ( 28‐day = 11.3 , 49‐day = 5.8 mean days , P = .005 ) . The number of spotting days was similar between both schedules in the first trimester ( 28‐day = 4.8 , 49‐day = 3.7 mean days , P = .24 ) and continued into the fourth trimester ( 28‐day = 3.4 , 49‐day = 2.9 mean days , P = .30 ) . Annual expenditure for hygiene products was significantly less for extended use subjects ( 28‐day = $ 41.45 , 49‐day = $ 17.54 spent , P < .001 ) . CONCLUSION Extension of the 28‐day oral contraceptive ( OC ) cycle to a 49‐day cycle result ed in fewer bleeding days and no increase in mean spotting days or bleeding episodes We investigated the effect of oral contraceptives with low and high estrogen concentration on blood coagulation and thrombogenesis , induced by vascular subendothelium of rabbit aorta exposed to flowing human blood . Twenty healthy women intending to take oral contraceptives were studied [ 1 ] before drug ingestion ( control ) , and subsequently during the intake of oral contraceptives with [ 2 ] low estrogen content ( 20 micrograms ethinyl estradiol and 150 micrograms desogestrel per day ) and [ 3 ] high estrogen content ( 50 micrograms ethinyl estradiol and 125 micrograms desogestrel per day ) . All experiments were performed between day 17 and 21 of the menstrual cycle and drug effects were studied during the third tablet cycle . Deposition of fibrin , platelets and platelet thrombi on vascular subendothelium was tested at a defined blood flow and wall shear rate ( 10 ml/min , 650 s-1 ) and was quantified by morphometrical techniques . Treatment with the low and high dose contraceptive increased the plasma levels of ethinyl estradiol ( 728 + /- 139 and 1438 + /- 212 vs. 0 fmol/l [ low and high dose vs. control ] , means + /- SEM , P less than 0.001 ) and fibrinogen ( 2.3 + /- 0.1 and 2.6 + /- 0.1 vs. 2.0 + /- 0.1 g/l , P less than 0.05 ) ; and decreased antithrombin III activity ( 95 + /- 3 and 92 + /- 3 vs. 101 + /- 3 % , P less than 0.05 ) . Fibrin deposition on vascular subendothelium was enhanced by the high dose contraceptive only ( 47 + /- 4 vs. 35 + /- 4 % coverage of the subendothelial surface with fibrin , high dose vs. control , P less than 0.05 ) . The subendothelial deposition of platelets and platelet thrombi was not changed by contraceptive treatment . These results indicate that treatment with high dose contraceptives leads to an increase of fibrin-subendothelial interactions , whereas low dose contraceptives do not significantly alter the blood-subendothelium interactions . observed in this ex vivo model of thrombogenesis The contraceptive efficacy , cycle control , safety , and subject acceptance of the new contraceptive ( OC ) preparations containing gestodene ( GTD ) plus ethinyl estradiol ( EE ) are being compared with the combination containing desogestrel ( DSG ) plus EE in a r and omized , open-label outpatient study . Interim data from six cycles of this ongoing study were obtained for 378 women receiving 75 micrograms GTD + 30 micrograms EE per day and 384 women receiving 150 micrograms DSG + 30 micrograms EE per day . Each group received OCs for 21 days per cycle . There were no pregnancies in subjects receiving either OC during 1,658 cycles of GTD + EE or 1,707 cycles of DSG + EE use . The continuation rates were similar in the two groups , and no major differences in type or incidence of side effects were observed . There were also no clinical ly significant changes in blood pressure or body weight in either group . Slightly better cycle control was observed for subjects taking GTD + EE , since the incidence of spotting and breakthrough bleeding was slightly greater for women taking DSG + EE . The incidence of amenorrhea ( missed periods ) tended to be lower for the subjects taking the GTD-containing preparation : 7 ( 0.5 % ) cycles compared with 12 ( 0.9 % ) DSG + EE cycles . The GTD + EE-treated subjects also had a lighter menstrual flow . Fewer subjects taking GTD + EE withdrew because of side effects typically associated with OCs . The data from this study indicate that the new combination of GTD + EE provides safe and effective oral contraception , with good tolerance and cycle control OBJECTIVE This study was undertaken to compare the effects of 2 oral contraceptive regimens on menstrual cycle control and laboratory findings . METHODS In a multicenter r and omized study 100 microg levonorgestrel with 20 microg ethinyl estradiol ( Alesse or Loette ) was given to 155 healthy women . A triphasic preparation of 500 , 750 , and 1000 microg norethindrone with 35 microg ethinyl estradiol ( Ortho-Novum 7/7/7 or TriNovum ) was given to 167 women for 1 to 4 cycles of treatment . RESULTS Overall , the percentages of normal menstrual cycles and the percentages of cycles with intermenstrual and withdrawal bleeding were similar between the 2 treatment groups . In the levonorgestrel with ethinyl estradiol group , there was a statistically significantly longer latent period and a statistically significantly shorter withdrawal bleeding episode . Adverse events were similar between treatment groups , and none were serious . Most mean changes from baseline laboratory values were comparable between groups , although the mean increase in cholesterol concentration was statistically significantly lower in the levonorgestrel with ethinyl estradiol group . Changes in triglyceride and glucose concentrations were not statistically significantly different between groups . CONCLUSIONS Levonorgestrel ( 100 microg ) with ethinyl estradiol ( 20 microg ) provides menstrual cycle control equivalent to that obtained with triphasic norethindrone with ethinyl estradiol ( 75 % higher estrogen dose ) with similar safety and tolerability This study was design ed to determine the effects of two low-dose oral contraceptives , most frequently given in our area , monophasic desogestrel/ethinylestradiol ( DG/EE ) and triphasic levonorgestrel/ethinylestradiol ( LNG/EE ) , on lipoprotein parameters , especially LDL particle size and HDL subclass distribution ( determined by lipid-stained 2%-20 % polyacrylamide gradient gel electrophoresis ) in 37 healthy normolipidemic women aged 19 to 27 years . Lipid and lipoprotein parameters were measured before the start of treatment and in the third month of oral contraceptive use . Results reflected the estrogen-progestin balance . As compared with baseline values , with both formulations , plasma total cholesterol , phospholipids , and HDL3 cholesterol increased , and LDL-predominant peak size decreased , with a translation of LDL pattern A towards pattern I. With DG/EE , plasma triglycerides , apolipoproteins AI and B increased . With LNG/EE , LDL cholesterol increased , and HDL2 cholesterol decreased . All these modifications were moderate , within threshold limits . Estrogen-dominant monophasic DG/EE appears to be more favorable than progestin-dominant triphasic LNG/EE , since the reduction in LDL-predominant peak size is not associated with an increase in LDL cholesterol or with a decrease in HDL2 cholesterol The changes in haemostasis during oral contraception are related to the ethinylestradiol dose present in the formulation taken by the patient . An open , r and omized longitudinal study was performed to evaluate and compare the effects that low-dose oral contraceptives ( OCs ) containing different doses of ethinylestradiol exert on the haemostatic system . Eighty-nine healthy women , aged 18 - 45 years , were r and omly assigned to treatment with 3 different OCs : a monophasic pill containing 30 micrograms of ethinylestradiol plus 75 micrograms of gestodene ( GSD/30 ) ( 30 subjects ) , a triphasic pill containing levonorgestrel ( TRI/LNG ) ( 28 subjects ) , a monophasic pill containing 20 micrograms ethinylestradiol plus 150 micrograms of desogestrel ( DOG/20 ) ( 31 subjects ) . From every woman , blood sample s were collected before treatment and at the 3rd and 6th cycle of pill intake . The number of platelets significantly increased ( p less than 0.01 ) during treatment with TRI/LNG . Fibrinogen plasma values were significantly increased ( p less than 0.05 ) only in women treated with the preparation GSD/30 . Fibrinopeptide A ( FPA ) plasma levels significantly increased ( p less than 0.01 ) during treatment with the pills TRI/LNG and GSD/30 , but the levels of FPA were unchanged in the group treated with DOG/20 . The overall results of this study confirm that the effects of OCs on haemostasis are dependent on the ethinylestradiol dose . Moreover , they suggest that with reduction of the ethinylestradiol component to 20 micrograms , the effects of OCs on haemostasis seem to be virtually eliminated To determine a possible influence of two different hormonal contraceptives on bacterial microflora of gingival sulcus , subgingival plaque sample s of 29 healthy women aged between 20 and 32 years were investigated bacteriologically before subjects took a contraceptive and 10 and 20 days after subjects started the medication . In 14 women , and oral contraceptive containing 0.02 mg ethinyl estradiol and 0.15 mg desogestrel ( preparation A ) was used , and 15 women took a contraceptive containing 0.03 mg ethinyl estradiol and 2.00 mg dienogest ( preparation B ) daily over 21 days . There were no changes in clinical parameters of the teeth investigated during 3 weeks of the study . The periodontopathogenic bacteria Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans were never detected throughout the study . On the other h and , the periodontopathogenic species Prevotella intermedia was found in plaque sample s of 22 women . The content of this microorganism showed only a little change between the pretreatment period and plaque sampling after 10 days of contraceptive treatment , but a striking increase occurred after 20 days of contraceptive treatment , especially in the preparation A group . In this respect , there was a significant difference between preparations A and OBJECTIVES To comparatively evaluate the impact of a balanced one-third dose-reduced oral contraceptive on hemostatic variables . METHODS In an open-label , r and omized study , a dose-reduced oral contraceptive containing 20 microg of ethinylestradiol ( EE ) and 100 microg of levonorgestrel ( LNG ) was compared with a reference preparation containing 30 microg of EE and 150 microg of LNG . One-year data were obtained from 48 volunteers . RESULTS The direction and magnitude of the changes ( increase or decrease ) in most of the hemostatic variables were similar in both treatment groups . The majority of changes of all investigated variables remained within the reference ranges of variation . The procoagulatory variables increased to some extent from baseline to treatment cycle 13 , while the anticoagulatory variables slightly decreased . In particular , thrombin turnover measured by prothrombin fragments 1 + 2 increased during treatment by 35 % in the 20 microg of EE group and by 38 % in the 30 microg of EE group . Statistically significant differences between the two treatment groups were found only for TAT . For the profibrinolytic variables , plasminogen was increased by 42 % ( 20 microg of EE ) and 49 % ( 30 microg of EE ) . While the plasma levels of tPA antigen were reduced during treatment , the levels of its activity were increased by 54 % ( 20 microg of EE ) and 20 % ( 30 microg of EE ) . For PAI , both antigen and activity were decreased , somewhat more pronounced with 20 microg of EE . D-Dimer remained virtually unchanged . Finally , the median FbDP levels were elevated by 30 % ( 20 microg of EE ) and 38 % ( 30 microg of EE ) BACKGROUND Women often stop hormonal contraception because of perceived weight change . We conducted a r and omized trial comparing the contraceptive vaginal ring to a low-dose oral contraceptive ( OC ) . We examined the difference between women 's reported and measured baseline weights and looked at factors affecting perceived weight change . METHODS We r and omized 201 participants to either the vaginal ring or an OC for three cycles . We weighed participants upon enrollment ( n=194 ) and at exit ( n=167 ) , using the same instrument for all measurements . Participants also provided self-reported height and their reactions to perceived weight changes . RESULTS Baseline weight and body mass index were similar for both groups ( mean weight=145.9 lb ) . Measured weight was , on average , 4.4 lb more than reported weight ; this difference was greater in overweight and obese participants . Participants gained an average of 2.8 lb over 3 months ; this gain did not differ between groups or by baseline weight . Subjects who reported a " bad change " in weight at exit ( n=34 ) gained an average of 4.4 lb , whereas those who reported " no change " ( n=112 ) gained 2.2 lb and those who reported a " good change " ( n=14 ) gained 3.3 lb . CONCLUSION Participants underreported their weight , and this difference was greater for heavier women . There was little weight change for the women in our study . Participants ' opinions about weight change were not correlated with measured weight changes We investigated the effects of ethinylestradiol dose ( 50 , 30 and 20 microg ) and progestogen type [ desogestrel ( DSG ) , gestodene ( GSD ) , levonorgestrel ( LNG ) and norgestimate ( NGM ) ] in oral contraceptives on 24 hemostatic variables . In a multicenter , r and omized , comparative study , 707 healthy , nonsmoking , nulliparous women were treated for six cycles with one of the seven monophasic oral contraceptives tested . Significantly greater increases in prothrombin fragment 1 + 2 and factor VII ( activity and antigen ) , were found in the DSG , NGM and GSD groups compared to the LNG group . Similarly , significantly lower levels of protein S ( free and total ) and increased APC-sr ( endogenous thrombin potential based ) were found in the same groups compared with the LNG group . In addition , the estradiol dose ( 50 vs. 30 microg ) significantly influenced these parameters . All changes were within the normal range and have not been associated with an increased risk of venous thromboembolic event ( VTE ) . However , raised levels of these variables are associated with prothrombotic states such as pregnancy . The significance of the haemostatic changes found in this study in relation to VTE risk remains to be determined , but results of this study probably can not explain the differences in risk of VTE between OCs containing different progestogens Lowering the total steroid dose in modern oral contraceptives ( OCs ) has been connected with a higher incidence of ovarian follicle and cyst formation . To investigate the presence of ovarian follicles and cysts by means of vaginal ultrasonography and serum hormone determinations during use of two low-dose OCs , 65 volunteers were r and omized to receive either 20 micrograms ethinylestradiol ( EE ) + 150 micrograms desogestrel ( group A ) or 35 micrograms EE + 250 micrograms norgestimate ( group B ) for a 2-month study period . At baseline , 39 % of women in group A and 31 % in group B exhibited at least one follicle < 35 mm in diameter . By the end of the second treatment cycle , the frequency of these follicles had decreased to 14 % in each group . Only one subject in the higher estrogen group developed an ovarian cyst > 35 mm . One subject in each group demonstrated hormone levels characteristic of ovulation ; no pregnancy occurred in either group . The 20 micrograms EE preparation was not found to lead more often to ovarian follicles or cysts when compared with a 35 micrograms EE preparation , possibly because of the type and dose of the progestogen used This long-term , open-label multicenter study investigated the clinical efficacy and tolerability of a monophasic oral contraceptive containing 20 micrograms ethinylestradiol and 75 micrograms gestodene . A total of 670 women between the ages of 18 and 45 years received the trial preparation over a 3-year period , giving 19,095 evaluable cycles . Of the 670 participants in the study , 75 % completed at least 24 cycles with the trial preparation and 46 % remained in the study for the full 3 years . One pregnancy occurred during the study which was considered by the investigator to be the result of misuse of the drug , giving an uncorrected Pearl Index of 0.07 . Cycle control with the trial preparation was good , especially in women who did not miss any pills . By cycle 3 , only 10.2 % of women who had not missed pills reported intermenstrual bleeding ( scanty or medium/excessive bleeding ) and this decreased to 2.3 % by cycle 36 . The preparation was well tolerated , with a low incidence of unprompted adverse events . There were no clinical ly significant changes in mean body weight or blood pressure . Over the 3 years of the study , 10 % of women withdrew from the study for reasons related mostly to mild adverse events . Results from this study demonstrate that the trial preparation is a reliable and well-tolerated oral contraceptive that provides good cycle control In a double-blind , controlled , r and omized , four-arm , bicentric clinical study , the effect of four oral contraceptives ( OCs ) on various hormone parameters and serum-binding globulins was investigated . Four groups with 25 volunteers each ( 18 - 35 years of age ) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol ( EE ) + 2 mg dienogest ( DNG ) ( 30EE/DNG ) , 20 microg EE + 2 mg DNG ( 20EE/DNG ) , 10 microg EE + 2 mg estradiol valerate ( EV ) + 2 mg DNG ( EE/EV/DNG ) or 20 microg EE + 100 microg levonorgestrel ( LNG ) ( EE/LNG ) . The study was completed by 91 subjects . Blood sample s were taken after at least 12 h of fasting on Day 21 - 26 of the preceding control cycle and on Day 18 - 21 of the first , third and sixth treatment cycle . The serum concentrations of free testosterone were significantly decreased by about 40 - 60 % in all four groups , while those of dehydroepi and rosterone sulfate ( DHEAS ) showed a time-dependent decrease during treatment . Except for EE/EV/DNG , which increased prolactin significantly during the third and sixth cycles , no change was observed with the EE-containing preparations . There was a significant increase in the levels of serum-binding globulins during treatment , which differed according to the composition of the OCs used . The rise in sex hormone-binding globulin ( SHBG ) was highest during intake of 30EE/DNG ( + 320 % ) and lowest with EE/LNG ( + 80 % ) , while the effect of 20EE/DNG and EE/EV/DNG was similar ( + 270 % ) . The thyroxine-binding globulin ( TBG ) levels increased significantly , by 50 - 60 % , during treatment with the DNG-containing formulations , while the effect of EE/LNG was less significant ( + 30 % ) . The rise in corticosteroid-binding globulin ( CBG ) , which occurred in all groups , was most pronounced in women treated with 30EE/DNG ( + 90 % ) and least with EE/EV/DNG ( + 55 % ) , indicating a strong influence of EE and no effect of the progestogen component . In all treatment groups , the frequency of intracyclic bleeding rose in the first treatment cycle and decreased thereafter . Cycle control was significantly better with 30EE/DNG or EE/LNG than with 20EE/DNG or EE/EV/DNG . There was no significant change in blood pressure , body mass index or pulse rate throughout the study . In conclusion , the DNG-containing OCs caused a higher rise in SHBG and TBG levels than the LNG-containing preparation . The effects on CBG suggest a lesser hepatic effect of 2 mg EV as compared to 20 or 30 microg EE . In contrast to EE , the use of estradiol in OCs appeared to increase prolactin release , while the cycle control was better with the OC containing 30 microg EE BACKGROUND The risk of thromboembolic events related to the ethinyl estradiol ( EE ) dose in oral contraceptive ( OC ) pills has led to a further dose reduction . METHODS An OC pill with 150 micrograms desogestrel combined with only 20 micrograms EE was compared with a pill containing the same dose of desogestrel but 30 micrograms of EE in a Sc and inavian multicentre study with follow-up visits after 3 , 6 and 12 months . RESULTS In almost 5,000 cycles with each pill the numbers of pregnancies due to method failure with the lower and higher EE dose pills were 0 and 2 , respectively . Irregular bleedings were slightly more common with the lower EE dose , but tended to decrease over the year of study . Other side effects were uncommon . Regarding metabolic effects , both pills tended to raise the plasma HDL level and the lower EE dose pill also reduced LDL . Free testosterone was reduced by two-thirds with both pills , showing beneficial effects on acne . CONCLUSIONS It is concluded that both these pills are reliable and safe , but that many women would accept a slightly greater risk of irregular bleeding with the 20 micrograms EE dose pill in exchange for a reduction in potential risk related to the estrogenic component of OC pills OBJECTIVE : To compare bleeding patterns between a 21/7-day triphasic norgestimate/ethinyl estradiol ( E2 ) 25-microgram oral contraceptive pill ( OCP ) and a 24/4-day drospirenone/ethinyl E2 20-microgram OCP . METHODS : In a three-cycle , open-label , multicenter study , healthy , sexually active women were assigned r and omly to a 21/7-day ( norgestimate/ethinyl E2 ) or 24/4-day ( drospirenone/ethinyl E2 ) OCP regimen . R and omization was stratified to assure a balanced distribution between regimens for “ fresh starts ” and “ switchers . ” Bleeding data were collected daily using an interactive voice-response system . Bleeding was defined according to the 2007 U.S. Food and Drug Administration ’s Reproductive Health Drug Advisory Committee – endorsed criteria . RESULTS : Across the three cycles , the 21/7-day OCP group ( n=165 ) reported fewer unscheduled bleeding days than did the 24/4-day OCP group ( n=167 ) ( mean 4.6 compared with 6.1 days , P=.003 ) . Women using the 21/7-day OCP had significantly fewer episodes of unscheduled bleeding than did those using the 24/4-day OCP ( mean 1.47 compared with 2.01 , P=.001 ) . Moreover , women using the 21/7-day OCP had a significantly lower absence of scheduled bleeding at each cycle ( P<.001 ) . Both regimens were well-tolerated . CONCLUSION : A 21-day norgestimate/ethinyl E2 25-microgram regimen results in less unscheduled bleeding and more scheduled bleeding than does a 24-day drospirenone/ethinyl E2 20-microgram regimen . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . Clinical Trials.gov , NCT00745901 . LEVEL OF EVIDENCE : Objective : This study compared 84-day bleeding patterns after immediate initiation of a triphasic oral contraceptive with a 25-&mgr;g daily dose of ethinyl estradiol ( E2 ) compared with the contraceptive vaginal ring , which has a 15-&mgr;g daily dose of ethinyl E2 . Methods : This was an open-label controlled trial . We r and omly assigned 201 women to immediate start of a contraceptive pill or immediate start of the ring in a 1:1 allocation ratio . Our primary outcome was difference in mean bleeding – spotting days per woman according to treatment assignment . Secondary outcomes were differences in World Health Organization — defined menstrual indices , differences in perceived bleeding changes , and differences in bleeding according to cycle day at the start of method . Results : The mean bleeding – spotting days in the 84-day reference period for all subjects was 19.2 days ( 17.0 days for ring users and 21.4 days for pill users , mean difference 4.4 days ) . Using the World Health Organization menstrual indices , the ring users experienced fewer days or episodes of bleeding – spotting and shorter intervals . Among ring users , no baseline characteristics were associated with bleeding outcomes . Older nulliparous pill users , however , reported more bleeding – spotting days . Significantly more ring users reported a decrease in duration of bleeding compared with pill users ( P < .01 ) . We found no significant differences in bleeding patterns based on analysis of cycle day at study enrollment . Conclusion : Our study shows advantageous bleeding patterns for subjects using the contraceptive vaginal ring . It also confirms our previous findings that immediate start of hormonal contraception is an acceptable alternative to waiting for menses . Level of Evidence : OBJECTIVE To determine in a prospect i ve study if the use of two low-dose estrogen oral contraceptives is associated with changes in weight or body composition . DESIGN 80 out patients referring to the family planning service , aged 18 - 43 years were r and omly assigned to a treatment with the EE/desogestrel or EE/gestodene association , 20 patients with IUD , aged 26 - 40 years , were selected as a control group . Anthropometric data and body composition were taken at enrollment and after 6 and 12 months . MAIN OUTCOME MEASURES Anthropometric measurements included body mass index ( BMI ) , body composition estimated by mean of Bioelectrical Impendance Analysis ( BIA ) . RESULTS In the three groups weight , BMI , and total body water ( TBW ) , and body cellular mass ( BCM ) remained unchanged during the study period . CONCLUSIONS The use of EE/desogestrel and EE/gestodene is not associated with significant variations of body weight and body composition during one year treatment The objective of the study was to determine the suppressive effect on ovarian activity of 20 micrograms ethinylestradiol plus 75 micrograms gestodene administered for 21 or 23 days . The study was design ed as a double-blind , r and omized , multicenter trial in 60 women . A pre-treatment cycle , three treatment cycles and a post-treatment period were monitored by ovarian ultrasound and by LH , FSH , 17 beta-estradiol and progesterone measurements every other day . No ovulation and no luteinized , unruptured follicle were observed . Suppression of ovarian activity was more pronounced by the 23-day regimen . 17 beta-Estradiol serum levels during the last six days of a cycle and during the first six days of the next cycle were significantly less ( p < 0.05 ) in the 23-day regimen . The superiority of the 23-day regimen in comparison to the 21-day regimen with regard to the suppression of ovarian activity was shown in this study . The observed differences in the 17 beta-estradiol levels and follicular development between a 21-day and 23-day preparation combine to suggest that shortening the pill-free interval in combined oral contraceptives may increase the contraceptive safety margin in women on low-dose formulations OBJECTIVE Our purpose was to test the hypothesis that omitting the first three pills of the contraceptive cycle leads to ovulation . STUDY DESIGN Ninety-nine women , r and omly assigned to 1 of 3 treatments of combined oral contraceptives , completed the study . Treatments contained ethinyl estradiol and either monophasic gestodene , triphasic gestodene , or monophasic desogestrel . Pituitary-ovarian activity was monitored by ultrasonography of the ovaries and assay of serum concentrations of estradiol , progesterone , and follicle-stimulating hormone over 1 normal cycle ( study period 1 ) and 1 cycle after an extended pill-free interval of 10 days ( study period 2 ) . RESULTS None of the women experienced normal ovulation as evaluated by ultrasonography and serum progesterone concentrations . However , follicle-stimulating hormone reached a maximal serum concentration in most women during the first 7 pill-free days , indicating complete pituitary recovery , and increases in serum estradiol concentrations were seen in each woman although with marked interindividual variation . During study period 2 we found follicles of > 18 mm in 24 % , 24 % , and 40 % of the monophasic gestodene , triphasic gestodene , and monophasic desogestrel groups , respectively . CONCLUSIONS Follicular growth up to preovulatory size is common in women missing the first one to three pills of their contraceptive cycle . Although this creates the prerequisite for ovulation , normal ovulation did not occur when pill omissions were limited to only 3 days Oral contraceptive use is known to cause changes in the haemostatic system . These changes are thought to be related to oestrogen dose and to provide a possible link between the increased risk of thromboembolic disease known to occur in women taking oestrogen containing oral contraceptives . This study measured whole blood platelet activation , serially , in women taking oral contraceptives containing 20 micrograms and 30 micrograms ethinyloestradiol combined with desogestrel . Increased levels of ADP and arachidonic acid induced aggregation were observed in women taking the 30 micrograms ethinyloestradiol combination . Platelet release of beta-thromboglobulin ( beta TG ) was also significantly increased . Increased collagen induced aggregation was observed but this failed to reach statistical significance for the individual treatment groups . In women taking the 20 micrograms ethinyloestradiol combination , a significant increase was only observed when platelets were stimulated with arachidonic acid . Platelet factor 4 ( PF4 ) levels were unchanged in both groups . Significantly higher levels of beta TG were observed in women taking the 30 micrograms ethinyloestradiol combination compared with women taking the 20 micrograms ethinyloestradiol combination . These results show that oral contraceptive use is associated with platelet activation . Women taking the 20 micrograms ethinyloestradiol combination show less changes in platelet activation than women taking the 30 micrograms ethinyloestradiol combination . This lower dose pill may therefore be particularly suitable for high risk women wishing to use oral contraception The evaluation of the study was of the impact of oral contraceptive ( OC ) use on activated protein C ( APC-resistance ) . Eight hundred eighteen young fertile women were screened for a study design ed to compare three different marketed OC preparations . The women could have used either other oral contraceptive preparations before switching to the study medications ( switchers ) or were not using hormonal contraceptives ( new starters ) before the study began . Prior to study drug intake and during treatment , APC-resistance was determined with three different tests . Forty-one of 809 women evaluated ( 5.07 % ) carried the Factor V Leiden mutation . Twenty-two further participants ( 2.72 % ) had a positive screening test , but did not provide sample s for the confirmatory mutation test . Two women with homozygous Factor V Leiden mutations and 39 women with heterozygous mutations were identified . The homozygous carriers were identified in all three of the screening tests employed , whereas none of the tests detected all 39 heterozygotes . In the pretreatment screening tests , previous OC users ( switchers ) had slightly lower APC ratios than the women using non-hormonal birth control methods ( starters ) . During treatment the difference between starters and switchers was no longer apparent , but the APC ratio values of the screening tests slightly increased for both . The homozygous carriers were not treated . Differences in APC-resistance between users of the three different oral contraceptive preparations were not found . In conclusion , laboratory screening for APC-resistance using Coatest APC , ProC Global , or ProC APC-FV-Leiden clearly identifies homozygous mutant carriers . However , with regard to heterozygous mutant carriers , the sensitivity and specificity of the tests , especially during OC intake , is limited . The results of APC screening tests should have , at present , no impact on contraceptive counseling because the predictive value for thromboembolic risk of the test results and even the mutant status is low Fifty‐five women using Loestrin‐20 ( 20 μg ethinyl oestradiol and 1 mg norethisterone acetate ) as an oral contraceptive have been compared with a like number using Microgynon‐30 ( 30 μg ethinyl oestradiol and 150 μg levonorgestrel ) in a r and omized , double‐blind trial . Despite the small sample size , the main finding in the trial is clear‐cut ; Loestrin‐20 provides poor cycle control and is thus less acceptable as an oral contraceptive than Microgynon‐30 . Although there is also a suggestion that Loestrin‐20 may be less effective than Microgynon‐30 , the difference in the accidental pregnancy rates is not statistically significant Spotting and bleeding are among the most common side effects associated with oral contraceptive ( OC ) use and their occurrence is a prime determinant of whether a new user will continue to use OCs . Desogestrel and gestodene are two new progestins that were developed in part to minimize the occurrence of these side effects . Assessing the effect of these progestins is difficult , however , in part because their effects may be subtle , requiring a large sample size and possibly being overshadowed by other factors . To address these issues , we analyzed data from two comparative multicenter clinical trials that included 15,421 cycles among 2767 women . One study compared 75 micrograms gestodene + 30 micrograms ethinyl estradiol ( EE ) with 150 micrograms desogestrel + 30 micrograms EE , the other compared the same gestodene preparation with 150 micrograms desogestrel + 20 micrograms EE . Both studies found a higher risk of spotting or bleeding in all cycles among users of the desogestrel-containing preparation , with the differences ranging between 20 % and 70 % higher for the first study and 40 % and 140 % in the second . These differences were statistically significant in four of six cycles in each study and persisted after controlling for consistency and recency of OC use as well as smoking . After pooling the data and controlling for estrogen dose , the desogestrel-containing preparation was significantly associated with more frequent spotting or bleeding in five of six cycles . Smoking and consistency and recency of OC use were also independent predictors of spotting or bleeding This multicenter study compared the contraceptive efficacy , cycle control , and safety of a new triphasic norgestimate ( 180/215/250 microg)/ethinyl estradiol 25 microg regimen ( Ortho Tri-Cyclen Lo ) ( n = 1,723 ) with that of norethindrone acetate 1 mg/ethinyl estradiol 20 microg ( Loestrin Fe 1/20 ) ( n = 1,171 ) . Healthy women were treated for up to 13 cycles . Demographics were similar between regimens . Contraceptive efficacy was comparable for Ortho Tri-Cyclen Lo and Loestrin Fe 1/20 . The overall and method failure probabilities of pregnancy through 13 cycles were 1.9 % and 1.5 % , respectively , with Ortho Tri-Cyclen Lo and 2.6 % and 2.4 % , respectively , with Loestrin Fe 1/20 . Breakthrough bleeding and spotting was reported by a significantly lower percentage of participants in the Ortho Tri-Cyclen Lo group compared with the Loestrin Fe 1/20 group . At representative Cycles 1 , 3 , 6 , 9 , and 13 , breakthrough bleeding and spotting rates were 16.3 , 11.5 , 10.3 , 7.9 , and 7.7 % , respectively , in the Ortho Tri-Cyclen Lo group and 34.9 , 22.9 , 22.2 , 15.9 , and 13.1 % , respectively , in the Loestrin Fe 1/20 group . Compliance and safety data were similar for the two regimens OBJECTIVE To compare the effect of 2 oral contraceptives ( OCs ) on body weight . STUDY DESIGN A r and omized , parallel-group , multicenter study of 1,723 women taking an OC with norgestimate ( NGM ) 180/215/250 microg/ethinyl estradiol ( EE ) 25 microg vs. 1,171 women taking on OC with norethindrone acetate 1 mg/EE 20 microg for 6 - 13 cycles was performed . Body weight changes between baseline and cycle 6 and baseline and cycle 13 were analyzed . Analysis included not only changes in mean body weight but also the distribution of changes that were within 5 % of baseline weight , 5 - 10 % of baseline weight and > 10 % of baseline weight . Only the 10 % change was felt to be clinical ly significant . RESULTS The distribution of body weight changes did not statistically differ between the 2 OC groups for any parameter measured . The mean weight change after 6 months for the NGM/EE and norethindrone acetate/EE groups was + 0.71 kg and + 0.57 kg , respectively . At 13 cycles for the NGM/EE and norethindrone acetate/ EE groups , the mean body weight change was + 0.93 kg and + 0.62 kg , respectively . Only 0.3 % of subjects in both OC groups experienced a 10 % change in weight . CONCLUSION Use of OCs does not substantially affect body weight for most women This population -based case-control study assessed the effect of current use of monophasic or triphasic oral contraceptives ( OCs ) on the risk of functional ovarian cyst development . The cases were all 15 - 39-year-old enrollees in the Group Health Cooperative of Puget Sound who had either an inpatient primary diagnosis of functional ovarian cyst in 1988 or 1989 ( N=67 ) or an outpatient primary diagnosis of functional ovarian cyst from March 1988 through August 1989 at one of five Group Health Cooperative primary care clinics ( N=39 ) . Controls were r and omly selected enrollees matched to the cases for age , primary care clinic , and enrollment date ( N=255 ) . Subjects with previous hysterectomy or oophorectomy were excluded from this analysis . Pharmacy and medical record review showed that 16 % of cases and 19 % of controls were currently using monophasic OCs , whereas 11 % of cases and 9 % of controls were using triphasic OCs . Compared with women not using hormonal contraception , the relative risks of a diagnosed functional ovarian cyst among women currently using OCs were 0.8 ( 95 % confidence interval [ CI ] 0.4 - 1.8 ) for users of monophasic OCs and 1.3 ( 95 % CI 0.5 - 3.3 ) for users of triphasic OCs . In contrast to previous studies of monophasic OCs containing higher steroid dosages , the results of this study suggest that current use of low-dose monophasic OCs does not substantially decrease a woman 's risk of functional ovarian cyst formation . In addition , our results do not support recent speculation that current use of triphasic OCs appreciably increases the risk of functional ovarian cysts A statistically design ed study was carried out to determine an optimum combination of norgestimate and ethinyl estradiol as an oral contraceptive , based on efficacy , safety , and side-effect patterns . A total of 1,991 patients were studied for more than two years while they were receiving various dosage combinations of these steroids . There were seven dosage combinations studied as part of a statistically orthogonal experimental design , augmented by three combinations near the center . The data arising from these studies were used to fit approximate functions relating the amount of norgestimate and ethinyl estradiol to the rate of spotting and breakthrough bleeding , gastrointestinal disturbance , and pregnancies . These functions , in turn , helped to identify an optimum dosage ( 0.125 mg . of norgestimate plus 0.035 mg . of ethinyl estradiol ) in the entire range of combinations studied This prospect i ve , r and omized comparative clinical study involving 416 women investigated follicle development over a period of 12 oral contraceptive treatment cycles . Women were allocated to two groups , one group ( n = 207 ) received a preparation containing 30 micrograms ethinylestradiol and 75 micrograms gestodene daily , and the other group ( n = 209 ) received 20 micrograms ethinylestradiol and 150 micrograms desogestrel , daily . Follicular development was monitored by transvaginal ultrasonography of the ovaries , during days 18 - 21 in the pretreatment cycle and in treatment cycles 1 , 3 , 6 , 9 and 12 . Follicular development was found to be twice as frequent in the group receiving 20 micrograms ethinylestradiol/desogestrel as in the group receiving 30 micrograms ethinylestradiol/gestodene . For all cycles , follicles of 10 - 30 mm were found in 18 % of women in the desogestrel group , compared with 9.7 % in the gestodene group , whilst follicles with a diameter of > 30 mm were present in 5 % of the desogestrel group compared with 1.9 % of the gestodene group . The difference between the treatment groups with respect to follicle diameters of 10 - 30 mm and > 30 mm was statistically significant ( p < 0.05 and p < 0.001 , respectively ) . No ruptured follicles were observed in either group throughout the study , suggesting that there was no escape ovulation , however , there was one pregnancy in the desogestrel group that could not be explained either by drug interactions or missed pills . It can be concluded that the ethinylestradiol dose in an oral contraceptive has a significant effect on follicular ovarian activity , and that reducing the dose to 20 micrograms is associated with a significant increase in follicle size A r and omized controlled clinical trial comparing six combined oral contraceptives with 50 micrograms or less of ethinyl estradiol was undertaken in 10 WHO Collaborating Centres for Clinical Research in Human Reproduction . A total of 2430 women entered the trial and were observed for 28,077 woman-cycles . All low-dose combined oral contraceptives demonstrated equivalent efficiency with one-year pregnancy rates of one to six percent . However , discontinuation rates for medical reasons differed significantly between the treatment groups , with the preparation containing 20 micrograms ethinyl estradiol and that containing 400 micrograms norethisterone acetate being associated with higher discontinuation rates due to bleeding disturbances . Even among the preparations which did not differ in discontinuation rates , the reasons for discontinuation did differ . Women receiving norethisterone preparations tended to discontinue because of bleeding disturbances while those receiving the levonorgestrel-containing preparations tended to discontinue because of complaints of nausea and vomiting Contraceptive methods often induce disturbances in vaginal bleeding patterns which are the main reason for women to discontinue method use . Knowledge of these changes is essential for effective counselling and product development and necessitates adequate methods of collection and analysis of vaginal bleeding data . These issues were review ed by clinicians , medical statisticians and computer analysts during several consultations organized by the World Health Organization Special Programme of Research , Development and Research Training in Human Reproduction and their discussion s are summarized in this paper . Recommendations are made on the use of menstrual diary cards for data collection . It is suggested that the analysis of menstrual patterns be based on the reference period method developed by Rodriguez et al. in 1976 to which several modifications in terminology and choice of summary statistics are proposed . While these are presented as the minimum required for the comparability of studies , other points of analysis are identified which need further study , in an attempt to stimulate research in this field by other investigators In the present study the effect on the urinary excretion of vasoactive markers of two oral contraceptives ( OCs ) , i.e. , Leios , containing 0.02 mg ethinyl estradiol and 0.1 mg levonorgestrel , and Stediril 30 , containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel , was investigated . cGMP , prostacyclin and its antagonist thromboxane , serotonin , and urodilatin , a natriuretic and diuretic peptide formed in the kidney , were measured as markers . In a comparative , double-blind , r and omized , parallel group study , 34 women received Leios and 33 women Stediril 30 . Nocturnal urine was collected before treatment and during cyclic treatment after 3 and 12 cycles . Both contraceptives significantly enhanced cGMP excretion after 12 cycles . The prostacyclin metabolite remained unchanged for both formulations , but the excretion of the thromboxane metabolite was significantly decreased after 12 cycles . Thus , the ratio of prostacyclin to thromboxane , crucial for the result ing effect on vascular tone , increased significantly . For the serotonin metabolite , no changes were observed for both contraceptives . The excretion of urodilatin significantly increased for both preparations after 12 cycles compared to the pretreatment values . These results indicate that the low-dose OCs Leios and Stediril 30 may stimulate the production of some vasoactive markers , at least after 12 cycles of treatment . The positive influence of these contraceptives on the various markers investigated may improve vascular tone , impede development of atherosclerosis and arterial thrombosis , and improve water and electrolyte homeostasis . These effects most likely can be attributed to the estrogenic component . Levonorgestrel may elicit no impact on these estrogen-induced changes that , however , seem only to be manifested after a longer treatment period A comparative study of two low-dose oral contraceptives , gestodene ( GES ) 75 mcg/ethinyl oestradiol ( EE ) 30 mcg and desogestrel ( DES ) 150 mcg/EE 20 mcg , was conducted in women over 30 years of age . This r and omised , open-label study was organised in Denmark , Italy , New Zeal and and United Kingdom . A total of 505 women received GES/EE and 501 received DES/EE for 6 consecutive menstrual cycles . The two groups were comparable in terms of demographic and gynaecologic characteristics at baseline . However , the menstrual flow length was slightly longer in the GES/EE group before the start of the treatment . The mean age ( + /- SD ) was 35 + /- 4 years in the GES/EE group and 35 + /- 5 years in the DES/EE group . The subjects in the GES/EE group contributed data for a total of 2800 cycles and those in the DES/EE group , data for 2796 cycles . There were no pregnancies on medication with either preparation . The results showed that there were significantly more normal cycles in the GES/EE group for cycles 1 to 6 . Irregular bleeding between withdrawal bleeds occurred in 10 % of GES/EE and 18.5 % of DES/EE cycles . Absence of all bleeding was reported in 29 ( 1 % ) and 63 ( 2 % ) cycles , respectively . The incidence of missed pills was low in both groups ( 11 % of cycles ) . No significant differences were observed in cycle length or withdrawal bleeding episode length . Withdrawal bleeding mean intensity was statistically significantly greater with GES/EE . However , for both preparations , the mean intensity was close to light bleeding . No clinical ly significant differences were noted in weight , blood pressure , Papanicolaou smears or laboratory data . Sixty-eight ( 13.5 % ) subjects in the GES/EE group and 64 ( 12.8 % ) in the DES/EE group discontinued before the end of the study . Among them , 37 ( 7 % ) and 40 ( 8 % ) in the respective groups withdrew because of adverse reactions . There was no difference between groups in terms of primary reasons for withdrawal . The most frequently reported complaints that led to discontinuation in both groups were headache , nausea and metrorrhagia . Breast tenderness led to the discontinuation of 1 subject in the GES/EE group and 3 in the DES/EE group . These results show excellent cycle control , efficacy and very low rate of side effects with both GES/EE and DES/EE . These low-dose oral contraceptives could be well suited to healthy nonsmoking women requiring contraception up to the age of menopause 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 ( enrollment , 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 |
2,210 | 26,577,590 | Conclusions IVUS guidance was associated with improved clinical outcomes , especially in patients with complex lesions admitted with ACS . | Background Intravascular ultrasound ( IVUS ) can be a useful tool during drug-eluting stents ( DES ) implantation as it allows accurate assessment of lesion severity and optimal treatment planning .
However , numerous reports have shown that IVUS guided percutaneous coronary intervention is not associated with improved clinical outcomes , especially in non-complex patients and lesions . | Background — Prior small to modest-sized studies suggest a benefit of intravascular ultrasound ( IVUS ) guidance in noncomplex lesions . Whether IVUS guidance is associated with improved clinical outcomes after drug-eluting stent ( DES ) implantation in an unrestricted patient population is unknown . Methods and Results — Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents ( ADAPT-DES ) was a prospect i ve , multicenter , nonr and omized “ all-comers ” study of 8583 consecutive patients at 11 international centers design ed to determine the frequency , timing , and correlates of stent thrombosis and adverse clinical events after DES . Propensity-adjusted multivariable analysis was performed to examine the relationship between IVUS guidance and 1-year outcomes . IVUS was utilized in 3349 patients ( 39 % ) , and larger-diameter devices , longer stents , and /or higher inflation pressures were used in 74 % of IVUS-guided cases . IVUS guidance compared with angiography guidance was associated with reduced 1-year rates of definite/probable stent thrombosis ( 0.6 % [ 18 events ] versus 1.0 % [ 53 events ] ; adjusted hazard radio , 0.40 ; 95 % confidence interval , 0.21–0.73 ; P=0.003 ) , myocardial infa rct ion ( 2.5 % versus 3.7 % ; adjusted hazard radio , 0.66 ; 95 % confidence interval , 0.49–0.88 ; P=0.004 ) , and composite adjudicated major adverse cardiac events ( ie , cardiac death , myocardial infa rct ion , or stent thrombosis ) ( 3.1 % versus 4.7 % ; adjusted hazard radio , 0.70 ; 95 % confidence interval , 0.55–0.88 ; P=0.002 ) . The benefits of IVUS were especially evident in patients with acute coronary syndromes and complex lesions , although significant reductions in major adverse cardiac events were present in all patient subgroups those with including stable angina and single-vessel disease . Conclusions — In ADAPT-DES , the largest study of IVUS use to date , IVUS guidance was associated with a reduction in stent thrombosis , myocardial infa rct ion , and major adverse cardiac events within 1 year after DES implantation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00638794 OBJECTIVES This study sought to assess the impact of intravascular ultrasound ( IVUS ) guidance on clinical outcomes following drug-eluting stent implantation when treating long lesions . BACKGROUND The role of IVUS guidance when treating long lesions has been tested during bare-metal stent , but not during drug-eluting stent , implantation . METHODS A total of 543 patients treated with stents ≥ 28 mm in length were r and omly assigned to IVUS guidance ( n = 269 ) versus angiography guidance ( n = 274 ) . The primary endpoint was a composite of major adverse cardiac events ( MACE ) , including cardiovascular death , myocardial infa rct ion , target vessel revascularization , or stent thrombosis at 1 year following intervention . RESULTS In the intention-to-treat analysis , total stent length was 32.4 mm in the IVUS-guided arm versus 32.3 mm in angiography-guided arm ( p = 0.84 ) . Adjunct post-dilation was more frequently performed in the IVUS-guided arm ( 54.6 % vs. 44.5 % , p = 0.03 ) ; post-intervention minimal lumen diameters were similar ( 2.55 vs. 2.55 mm , respectively , p = 0.50 ) ; and MACE occurred in 12 ( 4.5 % ) patients in IVUS-guided arm and in 20 ( 7.3 % ) patients in the angiography-guided arm ( p = 0.16 ) . However , among the 269 patients assigned to IVUS guidance , IVUS was not used in 13 patients ( 4.8 % ) ; conversely , in 274 patients assigned to angiography alone , 41 patients ( 15.0 % ) were treated with IVUS guidance . Therefore , in a per- protocol analysis according to actual IVUS usage , minimum lumen diameter was larger ( 2.58 vs. 2.51 mm , p = 0.04 ) , and MACE rates were lower : 4.0 % in the IVUS-guided arm versus 8.1 % in the angiography-guided arm ( p = 0.048 ) . CONCLUSIONS A strategy of routine IVUS for drug-eluting stent implantation in long lesions did not improve the 1-year MACE rates . The IVUS use per operator decision was associated with improved results . ( A New Strategy Regarding Discontinuation of Dual Antiplatelet ; NCT01145079 ) BACKGROUND No r and omized studies have thus far evaluated intravascular ultrasound ( IVUS ) guidance in the drug-eluting stent ( DES ) era . The aim was to evaluate if IVUS optimized DES implantation was superior to angiographic guidance alone in complex lesions . METHODS R and omized , multicentre , international , open label , investigator-driven study evaluating IVUS vs angiographically guided DES implantation in patients with complex lesions ( defined as bifurcations , long lesions , chronic total occlusions or small vessels ) . Primary study endpoint was post-procedure in lesion minimal lumen diameter . Secondary end points were combined major adverse cardiac events ( MACE ) , target lesion revascularization , target vessel revascularization , myocardial infa rct ion ( MI ) , and stent thrombosis at 1 , 6 , 9 , 12 , and 24 months . RESULTS The study included 284 patients . No significant differences were observed in baseline characteristics . The primary study end point showed a statistically significant difference in favor of the IVUS group ( 2.70 mm ± 0.46 mm vs. 2.51 ± 0.46 mm ; P = .0002 ) . During hospitalization , no patient died , had repeated revascularization , or a Q-wave MI . No difference was observed in the occurrence of non-Q wave MI ( 6.3 % in IVUS vs. 7.0 % in angio-guided group ) . At 24-months clinical follow-up , no differences were still observed in cumulative MACE ( 16.9%vs . 23.2 % ) , cardiac death ( 0%vs . 1.4 % ) , MI ( 7.0%vs . 8.5 % ) , target lesion revascularization ( 9.2 % vs. 11.9 % ) or target vessel revascularization ( 9.8 % vs. 15.5 % ) , respectively in the IVUS vs. angio-guided groups . In total , only one definite subacute stent thrombosis occurred in the IVUS group . CONCLUSIONS A benefit of IVUS optimized DES implantation was observed in complex lesions in the post-procedure minimal lumen diameter . No statistically significant difference was found in MACE up to 24 months Background The importance of intravascular ultrasound (IVUS)-guided stenting of the unprotected left main coronary artery ( ULMCA ) remains controversial and has not been fully studied in the subset of patients with ULMCA . This study evaluated the clinical outcome of IVUS-guided stenting using a drug-eluting stent for ULMCA . Methods A total of 1,016 consecutive patients with ULMCA stenosis who underwent drug-eluting stent implantation from January 2006 to December 2011 were prospect ively registered . The primary endpoint of this nonr and omized registry was the rate of one-year major adverse cardiac events ( MACE , including cardiac death , myocardial infa rct ion , and target vessel revascularization ) . Stent thrombosis served as the safety endpoint . Propensity score matching was used to calculate the adjusted event rate . Results The unadjusted one-year MACE rate was 14.8 % in the IVUS-guided group ( n=337 , 33.2 % ) , significantly different from the 27.7 % ( P<0.001 ) in the angiography-guided group ( n=679 , 66.8 % ) . After propensity score matching , 291 paired patients were matched between the two groups , and the difference in one-year MACE between IVUS-guided ( 16.2 % ) versus angiography-guided ( 24.4 % ) groups was still significant ( P=0.014 ) , mainly driven by decreased rates of cardiac death ( 1.7 % ) and target vessel revascularization ( 3.4 % ) in the IVUS-guided group when compared with 5.2 % ( P=0.023 ) and 10.0 % ( P=0.002 ) in the angiography-guided group , respectively . Although it did not reach significance ( P=0.075 ) , the adjusted one-year rate of stent thrombosis in the angiography-guided group was higher than in the IVUS-guided group . Conclusion Compared with angiography guidance , IVUS-guided treatment of ULMCA using a drug-eluting stent was associated with a significant reduction of one-year cardiac death and target vessel revascularization , result ing in less frequent one-year MACE after propensity score matching OBJECTIVES This study sought to report the final 5 years follow-up of the l and mark LEADERS ( Limus Eluted From A Durable Versus ERodable Stent Coating ) trial . BACKGROUND The LEADERS trial is the first r and omized study to evaluate biodegradable polymer-based drug-eluting stents ( DES ) against durable polymer DES . METHODS The LEADERS trial was a 10-center , assessor-blind , noninferiority , " all-comers " trial ( N = 1,707 ) . All patients were central ly r and omized to treatment with either biodegradable polymer biolimus-eluting stents ( BES ) ( n = 857 ) or durable polymer sirolimus-eluting stents ( SES ) ( n = 850 ) . The primary endpoint was a composite of cardiac death , myocardial infa rct ion ( MI ) , or clinical ly indicated target vessel revascularization within 9 months . Secondary endpoints included extending the primary endpoint to 5 years and stent thrombosis ( ST ) ( Academic Research Consortium definition ) . Analysis was by intention to treat . RESULTS At 5 years , the BES was noninferior to SES for the primary endpoint ( 186 [ 22.3 % ] vs. 216 [ 26.1 % ] , rate ratio [ RR ] : 0.83 [ 95 % confidence interval ( CI ) : 0.68 to 1.02 ] , p for noninferiority < 0.0001 , p for superiority = 0.069 ) . The BES was associated with a significant reduction in the more comprehensive patient-orientated composite endpoint of all-cause death , any MI , and all-cause revascularization ( 297 [ 35.1 % ] vs. 339 [ 40.4 % ] , RR : 0.84 [ 95 % CI : 0.71 to 0.98 ] , p for superiority = 0.023 ) . A significant reduction in very late definite ST from 1 to 5 years was evident with the BES ( n = 5 [ 0.7 % ] vs. n = 19 [ 2.5 % ] , RR : 0.26 [ 95 % CI : 0.10 to 0.68 ] , p = 0.003 ) , corresponding to a significant reduction in ST-associated clinical events ( primary endpoint ) over the same time period ( n = 3 of 749 vs. n = 14 of 738 , RR : 0.20 [ 95 % CI : 0.06 to 0.71 ] , p = 0.005 ) . CONCLUSIONS The safety benefit of the biodegradable polymer BES , compared with the durable polymer SES , was related to a significant reduction in very late ST ( > 1 year ) and associated composite clinical outcomes . ( Limus Eluted From A Durable Versus ERodable Stent Coating [ LEADERS ] trial ; NCT00389220 ) Objective : To assess the role of the intravascular ultrasound ( IVUS ) during implantation of Drug‐eluting stents ( DES ) on long‐term outcome in patients with complex coronary artery disease and high clinical risk profile with special attention to the development of late stent thrombosis ( LST ) . Methods : Two hunderd and ten patients were r and omly assigned to receive DES either with ( N = 105 ) or without ( N = 105 ) the IVUS guidance . Dual antiplatelet treatment was administered for 6 months in all patients . At 18‐month follow‐up , the rates of Major adverse cardiac events ( MACEs ) ( death , myocardial infa rct ion , and reintervention ) were assessed in both groups with special attention to possible LST . Stent thrombosis was classified according to Academic Research Consortium ( ARC ) . Results : At the 18‐month follow‐up , there was no significant difference between both groups regarding MACE ( 11 % vs. 12 % ; P = NS ) . Stent thrombosis has occurred in four patients ( 3.8 % ) in the group with and in 6 patients ( 5.7 % ; P = NS ) in the group without the IVUS guidance . Conclusions : In our r and omized trial we failed to demonstrate the superiority of the IVUS guidance during DES implantation over st and ard high‐pressure postdilatation . However we confirmed worrisome results concerning DES thrombosis after discontinuation of dual antiplatelet‐treatment with documented stent thrombosis related events in almost 5 % of patients with 50 % of mortality in this high‐risk clinical scenario . © 2009 Wiley‐Liss , OBJECTIVES This study sought to assess the impact of intravascular ultrasound (IVUS)-guided versus angiography-guided drug-eluting stent ( DES ) implantation . BACKGROUND There are limited data on IVUS guidance in the DES era . Therefore , we investigated the impact of IVUS guidance on clinical outcomes in the MATRIX ( Comprehensive Assessment of Sirolimus-Eluting Stents in Complex Lesions ) registry . METHODS The MATRIX registry prospect ively enrolled consecutive , unselected patients treated with sirolimus-eluting stents ( SES ) ( n = 1,504 ) ; 631 patients ( 42 % ) underwent IVUS-guided stenting , and 873 ( 58 % ) had only angiographic guidance . We assessed 30-day , 1-year , and 2-year rates of death/myocardial infa rct ion ( MI ) , major adverse cardiac events ( cardiac death , MI , or target vessel revascularization ) , and definite/probable stent thrombosis in 548 propensity-score matched patient pairs . RESULTS After matching , baseline and angiographic characteristics were similar in IVUS and no-IVUS groups . Patients in the IVUS group had significantly less death/MI at 30 days ( 1.5 % vs. 4.6 % , p < 0.01 ) , 1 year ( 3.3 % vs. 6.5 % , p < 0.01 ) , and 2 years ( 5.0 % vs. 8.8 % , p < 0.01 ) . Patients in the IVUS group had significantly less major adverse cardiac events at 30 days ( 2.2 % vs. 4.8 % , p = 0.04 ) and numerically less major adverse cardiac events at 1 year ( 9.1 % vs. 13.5 % , p = 0.07 ) and 2 years ( 12.9 % vs. 16.7 % , p = 0.18 ) . Rates of MI were significantly lower in the IVUS group at 30 days ( 1.5 % vs. 4.0 % , p < 0.01 ) , 1 year ( 1.8 % vs. 4.8 % , p < 0.01 ) , and 2 years ( 2.1 % vs. 5.7 % , p < 0.01 ) . CONCLUSIONS IVUS-guided stent implantation appears to be associated with a reduction in both early and long-term clinical events . Further investigation in r and omized controlled trials is warranted |
2,211 | 20,488,270 | It can be concluded that MBSR has small effects on depression , anxiety and psychological distress in people with chronic somatic diseases .
Integrating MBSR in behavioral therapy may enhance the efficacy of mindfulness based interventions | OBJECTIVES The objective of this study was to examine the effectiveness of mindfulness-based stress reduction ( MBSR ) on depression , anxiety and psychological distress across population s with different chronic somatic diseases . | Generalized anxiety disorder ( GAD ) is a chronic anxiety disorder , associated with comorbidity and impairment in quality of life , for which improved psychosocial treatments are needed . GAD is also associated with reactivity to and avoidance of internal experiences . The current study examined the efficacy of an acceptance-based behavioral therapy aim ed at increasing acceptance of internal experiences and encouraging action in valued domains for GAD . Clients were r and omly assigned to immediate ( n = 15 ) or delayed ( n = 16 ) treatment . Acceptance-based behavior therapy led to statistically significant reductions in clinician-rated and self-reported GAD symptoms that were maintained at 3- and 9-month follow-up assessment s ; significant reductions in depressive symptoms were also observed . At posttreatment assessment 78 % of treated participants no longer met criteria for GAD and 77 % achieved high end-state functioning ; these proportions stayed constant or increased over time . As predicted , treatment was associated with decreases in experiential avoidance and increases in mindfulness Background : Mindfulness-based stress reduction ( MBSR ) proposes a systematic program for reduction of suffering associated with a wide range of medical conditions . Studies suggest improvements in general aspects of well-being , including quality of life ( QoL ) , coping and positive affect , as well as decreased anxiety and depression . Methods : A quasi-experimental study examined effects of an 8-week MBSR intervention among 58 female patients with fibromyalgia ( mean , 52 ± 8 years ) who underwent MBSR or an active social support procedure . Participants were assigned to groups by date of entry , and 6 subjects dropped out during the study . Self-report measures were vali date d German inventories and included the following scales : visual analog pain , pain perception , coping with pain , a symptom checklist and QoL. Pre- and postintervention measurements were made . Additionally , a 3-year follow-up was carried out on a subgroup of 26 participants . Results : Pre- to postintervention analyses indicated MBSR to provide significantly greater benefits than the control intervention on most dimensions , including visual analog pain , QoL subscales , coping with pain , anxiety , depression and somatic complaints ( Cohen d effect size , 0.40–1.10 ) . Three-year follow-up analyses of MBSR participants indicated sustained benefits for these same measures ( effect size , 0.50–0.65 ) . Conclusions : Based upon a quasi-r and omized trial and long-term observational follow-up , results indicate mindfulness intervention to be of potential long-term benefit for female fibromyalgia patients The purpose of this study was to gather data on the efficacy of a newly developed psychosocial group intervention for cancer patients , called mindfulness-based art therapy ( MBAT ) . One hundred and eleven women with a variety of cancer diagnoses were paired by age and r and omized to either an eight-week MBAT intervention group or a wait-list control group . Ninety-three participants ( 84 % ) completed both the pre- and post- study measurements . As compared to the control group , the MBAT group demonstrated a significant decrease in symptoms of distress ( as measured by the Symptoms Checklist-90-Revised ) and significant improvements in key aspects of health-related quality of life ( as measured by the Medical Outcomes Study Short-Form Health Survey ) . This investigation of MBAT provides initial encouraging data that support a possible future role for the intervention as a psychosocial treatment option for cancer patients Recovered recurrently depressed patients were r and omized to treatment as usual ( TAU ) or TAU plus mindfulness-based cognitive therapy ( MBCT ) . Replicating previous findings , MBCT reduced relapse from 78 % to 36 % in 55 patients with 3 or more previous episodes ; but in 18 patients with only 2 ( recent ) episodes corresponding figures were 20 % and 50 % . MBCT was most effective in preventing relapses not preceded by life events . Relapses were more often associated with significant life events in the 2-episode group . This group also reported less childhood adversity and later first depression onset than the 3-or-more-episode group , suggesting that these groups represented distinct population s. MBCT is an effective and efficient way to prevent relapse/recurrence in recovered depressed patients with 3 or more previous episodes This study evaluated mindfulness-based cognitive therapy ( MBCT ) , a group intervention design ed to train recovered recurrently depressed patients to disengage from dysphoria-activated depressogenic thinking that may mediate relapse/recurrence . Recovered recurrently depressed patients ( n = 145 ) were r and omized to continue with treatment as usual or , in addition , to receive MBCT . Relapse/recurrence to major depression was assessed over a 60-week study period . For patients with 3 or more previous episodes of depression ( 77 % of the sample ) , MBCT significantly reduced risk of relapse/recurrence . For patients with only 2 previous episodes , MBCT did not reduce relapse/recurrence . MBCT offers a promising cost-efficient psychological approach to preventing relapse/recurrence in recovered recurrently depressed patients OBJECTIVE To assess the effect of a meditation training program , Mindfulness-Based Stress Reduction ( MBSR ) , on depressive symptoms , psychological status , and disease activity in patients with rheumatoid arthritis ( RA ) through a r and omized , waitlist-controlled pilot study . METHODS Participants were r and omized to either an MBSR group , where they attended an 8-week course and 4-month maintenance program , or to a waitlist control group , where they attended all assessment visits and received MBSR free of charge after study end . Participants received usual care from their rheumatologists throughout the trial . Self-report question naires were used to evaluate depressive symptoms , psychological distress , well-being , and mindfulness . Evaluation of RA disease activity ( by Disease Activity Score in 28 joints ) included examination by a physician masked to treatment status . Adjusted means and mean changes in outcomes were estimated in mixed model repeated measures analyses . RESULTS Sixty-three participants were r and omized : 31 to MBSR and 32 to control . At 2 months , there were no statistically significant differences between groups in any outcomes . At 6 months , there was significant improvement in psychological distress and well-being ( P = 0.04 and P = 0.03 , respectively ) , and marginally significant improvement in depressive symptoms and mindfulness ( P = 0.08 and P = 0.09 , respectively ) . There was a 35 % reduction in psychological distress among those treated . The intervention had no impact on RA disease activity . CONCLUSION An 8-week MBSR class was not associated with change in depressive symptoms or other outcomes at 2-month followup . Significant improvements in psychological distress and well-being were observed following MBSR plus a 4-month program of continued reinforcement . Mindfulness meditation may complement medical disease management by improving psychological distress and strengthening well-being in patients with RA OBJECTIVE To test the short and longterm benefits of an 8 week mind-body intervention that combined training in mindfulness meditation with Qigong movement therapy for individuals with fibromyalgia syndrome ( FM ) . METHODS A total of 128 individuals with FM were r and omly assigned to the mind-body training program or an education support group that served as the control . Outcome measures were pain , disability ( Fibromyalgia Impact Question naire ) , depression , myalgic score ( number and severity of tender points ) , 6 minute walk time , and coping strategies , which were assessed at baseline and at 8 , 16 , and 24 weeks . RESULTS Both groups registered statistically significant improvements across time for the Fibromyalgia Impact Question naire , Total Myalgic Score , Pain , and Depression , and no improvement in the number of feet traversed in the 6 minute walk . However , there was no difference in either the rate or magnitude of these changes between the mind-body training group and the education control group . Salutary changes occurring by the eighth week ( which corresponded to the end of the mind-body and education control group sessions ) were largely maintained by both groups throughout the 6 month followup period . CONCLUSION While both groups showed improvement on a number of outcome variables , there was no evidence that the multimodal mind-body intervention for FM was superior to education and support as a treatment option . Additional r and omized controlled trials are needed before interventions of this kind can be recommended for treatment of FM & NA ; The objectives of this pilot study were to assess the feasibility of recruitment and adherence to an eight‐session mindfulness meditation program for community‐dwelling older adults with chronic low back pain ( CLBP ) and to develop initial estimates of treatment effects . It was design ed as a r and omized , controlled clinical trial . Participants were 37 community‐dwelling older adults aged 65 years and older with CLBP of moderate intensity occurring daily or almost every day . Participants were r and omized to an 8‐week mindfulness‐based meditation program or to a wait‐list control group . Baseline , 8‐week and 3‐month follow‐up measures of pain , physical function , and quality of life were assessed . Eighty‐nine older adults were screened and 37 found to be eligible and r and omized within a 6‐month period . The mean age of the sample was 74.9 years , 21/37 ( 57 % ) of participants were female and 33/37 ( 89 % ) were white . At the end of the intervention 30/37 ( 81 % ) participants completed 8‐week assessment s. Average class attendance of the intervention arm was 6.7 out of 8 . They meditated an average of 4.3 days a week and the average minutes per day was 31.6 . Compared to the control group , the intervention group displayed significant improvement in the Chronic Pain Acceptance Question naire Total Score and Activities Engagement subscale ( P = .008 , P = .004 ) and SF‐36 Physical Function ( P = .03 ) . An 8‐week mindfulness‐based meditation program is feasible for older adults with CLBP . The program may lead to improvement in pain acceptance and physical function Objective The objective of this study was to assess the effects of participation in a mindfulness meditation – based stress reduction program on mood disturbance and symptoms of stress in cancer out patients . Methods A r and omized , wait-list controlled design was used . A convenience sample of eligible cancer patients enrolled after giving informed consent and were r and omly assigned to either an immediate treatment condition or a wait-list control condition . Patients completed the Profile of Mood States and the Symptoms of Stress Inventory both before and after the intervention . The intervention consisted of a weekly meditation group lasting 1.5 hours for 7 weeks plus home meditation practice . Results Ninety patients ( mean age , 51 years ) completed the study . The group was heterogeneous in type and stage of cancer . Patients ’ mean preintervention scores on dependent measures were equivalent between groups . After the intervention , patients in the treatment group had significantly lower scores on Total Mood Disturbance and subscales of Depression , Anxiety , Anger , and Confusion and more Vigor than control subjects . The treatment group also had fewer overall Symptoms of Stress ; fewer Cardiopulmonary and Gastrointestinal symptoms ; less Emotional Irritability , Depression , and Cognitive Disorganization ; and fewer Habitual Patterns of stress . Overall reduction in Total Mood Disturbance was 65 % , with a 31 % reduction in Symptoms of Stress . Conclusions This program was effective in decreasing mood disturbance and stress symptoms in both male and female patients with a wide variety of cancer diagnoses , stages of illness , and ages Summary : Heart disease is the leading cause of death among Americans each year , yet the misperception still exists that cardiovascular disease is not a serious health problem for women . Evidence indicates that anxiety contributes to the development of heart disease . The primary purpose of this study was to assess the effectiveness of Kabat-Zinn 's mindfulness-based stress reduction program to reduce anxiety in women with heart disease . Anxiety , emotional control , coping styles , and health locus of control were compared in a treatment and control group of women with heart disease . Post-intervention analyses provide initial support for beneficial effects of this program OBJECTIVE Depressive symptoms are common among patients with fibromyalgia , and behavioral intervention has been recommended as a major treatment component for this illness . The objective of this study was to test the effects of the Mindfulness-Based Stress Reduction ( MBSR ) intervention on depressive symptoms in patients with fibromyalgia . METHODS This r and omized controlled trial examined effects of the 8-week MBSR intervention on depressive symptoms in 91 women with fibromyalgia who were r and omly assigned to treatment ( n = 51 ) or a waiting-list control group ( n = 40 ) . Eligible patients were at least 18 years old , willing to participate in a weekly group , and able to provide physician verification of a fibromyalgia diagnosis . Of 166 eligible participants who responded to local television news publicizing , 49 did not appear for a scheduled intake , 24 enrolled but did not provide baseline data , and 2 were excluded due to severe mental illness , leaving 91 participants . The sample averaged 48 years of age and had 14.7 years of education . The typical participant was white , married , and employed . Patients r and omly assigned to treatment received MBSR . Eight weekly 2.5-hour sessions were led by a licensed clinical psychologist with mindfulness training . Somatic and cognitive symptoms of depression were assessed using the Beck Depression Inventory administered at baseline , immediately postprogram , and at followup 2 months after the conclusion of the intervention . RESULTS Change in depressive symptoms was assessed using slopes analyses of intervention effects over time . Depressive symptoms improved significantly in treatment versus control participants over the 3 assessment s. CONCLUSION This meditation-based intervention alleviated depressive symptoms among patients with fibromyalgia & NA ; This study reports chronic pain prevalence in a r and omly selected sample of the adult Australian population . Data were collected by Computer‐Assisted Telephone Interview ( CATI ) using r and omly generated telephone numbers and a two‐stage stratified sample design . Chronic pain was defined as pain experienced every day for three months in the six months prior to interview . There were 17,543 completed interviews ( response rate=70.8 % ) . Chronic pain was reported by 17.1 % of males and 20.0 % of females . For males , prevalence peaked at 27.0 % in the 65–69 year age group and for females , prevalence peaked at 31.0 % in the oldest age group ( 80–84 years ) . Having chronic pain was significantly associated with older age , female gender , lower levels of completed education , and not having private health insurance ; it was also strongly associated with receiving a disability benefit ( adjusted OR=3.89 , P<0.001 ) or unemployment benefit ( adjusted OR=1.99 , P<0.001 ) ; being unemployed for health reasons ( adjusted OR=6.41 , P<0.001 ) ; having poor self‐rated health ( adjusted OR=7.24 , P<0.001 ) ; and high levels of psychological distress ( adjusted OR=3.16 , P<0.001 ) . Eleven per cent of males and 13.5 % of females in the survey reported some degree of interference with daily activities caused by their pain . Prevalence of interference was highest in the 55–59 year age group in both males ( 17.2 % ) and females ( 19.7 % ) . Younger respondents with chronic pain were proportionately most likely to report interference due to pain , affecting 84.3 % of females and 75.9 % of males aged 20–24 years with chronic pain . Within the subgroup of respondents reporting chronic pain , the presence of interference with daily activities caused by pain was significantly associated with younger age ; female gender ; and not having private health insurance . There were strong associations between having interfering chronic pain and receiving disability benefits ( adjusted OR=3.31 , P<0.001 ) or being unemployed due to health reasons ( adjusted OR=7.94 , P<0.001 , respectively ) . The results show that chronic pain impacts upon a large proportion of the adult Australian population , including the working age population , and is strongly associated with markers of social disadvantage |
2,212 | 11,601,955 | The literature review did not identify any clinical trials of preventive counseling for osteoporosis .
Current smoking has been associated with lower bone mineral density ( BMD ) and increased risk for fracture after minimal trauma in most studies ( 2 ) .
In a follow-up multivariate analysis of the Study of Osteoporotic Fractures , axial BMD was positively associated with physical activity ( 53 ) . | Osteoporosis is a systemic skeletal disease characterized by low bone mass , microarchitectural deterioration of bone tissue , and a consequent increase in bone fragility and susceptibility to fracture ( 1 ) .
Approximately 10 million people in the United States , 80 % of whom are women , have osteoporosis , and another 18 million ( 83 % women ) have low bone mass ( 2 ) .
Osteoporosis is a major cause of morbidity and death in older persons .
The clinical complications of osteoporosis include fractures , most commonly vertebral , hip , and forearm ; disability ; deformity ; and chronic pain .
For women who are 50 years of age , the estimated lifetime risk for osteoporotic fracture is 54 % ( 3 ) .
For white men who are 50 years of age , the lifetime risk for hip fracture is an estimated 5 % to 6 % ( 2 ) .
Studies suggest that the prevalence of vertebral fractures is similar for men and women ( 4 , 5 ) .
Approximately 4 % of patients older than 50 years of age who experience a hip fracture will die while in the hospital , and 24 % will die within 1 year of experiencing hip fracture ( 6 ) .
In the United States in 1995 , osteoporotic fractures cost an estimated $ 13.8 billion ( 7 ) .
Numerous risk factors , both modifiable and nonmodifiable , have been identified for osteoporosis .
However , numerous studies have demonstrated the benefits of HRT on BMD and fracture risk .
These effects , which are detailed in the Table , include decreased rate of bone loss ( 28 ) ; increased BMD ( 29 , 30 ) ; and decreased risk for fracture of the spine ( 31 ) , hip ( 32 , 34 ) , and wrist ( 32 , 38 ) .
Also , a 4-year prospect i ve study of exercise in osteoporotic patients reported that exercise could improve quality of life by decreasing pain ( 54 ) .
Numerous guidelines support the use of weight-bearing exercise for the prevention and treatment of osteoporosis ( 1 , 13 , 15 , 16 , 45 , 46 , 48 , 55 ) . | We interviewed 327 women who had been 50 to 74 years of age when treated for fracture of the hip of lower forearm , to determine their use ( or lack of use ) of estrogen preparations . Their responses were compared with those in a r and om sample of 567 women who were of similar age and from the same region . The risk of fracture was 50 to 60 per cent lower in women who had used these drugs for six years or longer than in women who hadnot used them ( 95 per cent confidence interval of relative risk , 0.3 to 0.6 ) ; those using them for shorter periods received less benefit , if any . A decreased risk of fracture was clearly evident only in women still taking estrogens and evident at either common daily dose ( 0.625 and 1.25 mg ) . In conjunction with the finding that estrogens can retard the development of osteoporosis in postmenopausal women , our data argue that lowering of the risk of hip and forearm fractures must be weighed as a benefit of long-term estrogen use Summary To develop an improved treatment schedule for osteoporosis , a study was undertaken in 100 postmenopausal women using a modified ADFR 90-day cyclical regimen with etidronate . After one year of treatment , the etidronate-treated group showed a significant increase in bone density of the spine , which continued over the following 2 years of treatment and remained stable during the fourth year . In contrast , in the non-etidronate group , bone density decreased significantly after four years . In addition , the fracture rate was significantly lower in the etidronate group than in the non-etidronate group . Side effects were minimal in both groups and no serious adverse reactions were reported . In conclusion , it appears that a cyclical regimen using 1,25-dihydroxyvitamin D3 , etidronate and calcium increases bone mass and reduces fractures with no significant side effects , thus making a useful contribution in the treatment of postmenopausal osteoporosis OBJECTIVE : To define the effects of therapeutic exercise on bone density and back complaints . METHODS : A r and omised controlled trial with parallel groups was conducted in an outpatient clinic , Medical School , University of Vienna . Ninety two sedentary post-menopausal women with back problems were r and omly allocated to either exercise ( groups 1 and 2 ) or control ( group 3 , no exercise , n = 31 ) ; the exercise group was retrospectively subdivided into compliant ( group 1 , n = 27 ) and not fully compliant patients ( group 2 , n = 34 ) . Regular , initially supervised therapeutic exercise aim ed at restoring biomechanical function was performed for four years . Bone density in the forearm was measured by single photon absorptiometry at entry and after four years ; subjective back complaints were documented . RESULTS : A significant decrease in bone density was observed in groups 2 and 3 ; no change was noted in group 1 ; back complaints decreased in group 1 only . CONCLUSIONS : Sedentary postmenopausal women may benefit from regular long term therapeutic exercise in terms of subjective back complaints and slowed loss of bone mass A population -based case-control study was conducted to examine the effects of past and recent physical activity on the risk of hip fracture in women . Cases included females aged 55 - 84 years with a first diagnosis of hip fracture in 1989 in metropolitan Toronto , Canada . Controls were a population -based r and om sample frequency matched by 5-year age groups . Data were collected on 381 cases and 1,138 controls by self-administered mailed question naires or telephone interviews . Past activity was calculated as a compilation of activity scores at ages 16 , 30 , and 50 years . Recent activity was defined as activity in the past year for controls and activity in the year before fracture for cases . Multiple logistic regression was used to control for age , previous fracture , obesity , smoking , osteoporosis , epilepsy , stroke or Parkinson 's disease , daily intake of dietary calcium , and duration of use of supplemental calcium , fluoride , and estrogen . After recent activity was adjusted for , statistically significant effects were found for women who in the past had been active ( odds ratio estimate ( OR ) = 0.66 , 95 % confidence interval ( CI ) 0.45 - 0.96 ) or very active ( OR = 0.54 , 95 % CI 0.33 - 0.88 ) . After past activity was adjusted for , a similar protective effect was found for women who were moderately active recently ( OR = 0.61 , 95 % CI 0.41 - 0.90 ) , but women who were very active recently were not protected from hip fracture ( OR = 1.15 , 95 % CI 0.72 - 1.83 ) . This study showed evidence of independent protective effects of past physical activity and of moderate levels of recent physical activity on the risk of hip fracture in postmenopausal women Because of uncertainty about the place of hormones in the treatment of postmenopausal bone loss vertebral and forearm bone loss was measured by absorptiometry in early post-menopausal women before and after continuous or sequential treatment with combined oestrogen and progestogen in a double blind placebo controlled trial . Treatment with hormones significantly reversed the vertebral bone loss . The net gain in vertebral bone density amounted to 6·4 % a year with continuous supplementation and 5·4 % a year with sequential supplementation ; the net gain in forearm bone density was lower ( 3·6 % with continuous and 3·7 % with sequential supplementation ) . Before a policy of supplementation with hormones can be recommended to all postmenopausal women with the aim of reducing the incidence of vertebral crush fractures further studies with different doses and combinations of hormones , administered over several years , are needed The aims of this study were to ascertain vertebral deformity prevalence in elderly men and women and to describe the association between bone mineral density ( BMD ) at the lumbar spine and femoral neck , severity of spinal degenerative disease and vertebral deformity prevalence . We performed st and ardized spinal radiographs in a r and om sample of 300 elderly men and women participating in the Dubbo Osteoporosis Epidemiology Study , a population -based study of fracture risk factors . Radiographs were read independently by masked observers for the prevalence of vertebral deformity and severity of osteophytosis . BMD was measured by dual-energy X-ray absorptiometry . The prevalence of vertebral deformities was critically dependent on the criterion used . The less strict criteria seemed to overestimate deformities at either end of the spine region analysed . However , irrespective of the criterion used , prevalence of deformity was higher in men than in women ( 25 % vs 20 % for the 3 SD criterion , 17 % vs 12 % for the 4 SD criterion and 27 % vs 25 % for the 25 % criterion ) . Femoral neck BMD was more strongly associated with vertebral deformities than spinal BMD for the 25 % criterion ( OR/SD change in BMD 1.39 ( p=0.02 ) vs 1.20 ( p=0.19 ) ) , 3 SD criterion ( OR/SD change in BMD 1.45 ( p=0.01 ) vs 1.10 ( p=0.34 ) ) and 4 SD criterion ( OR/SD change in BMD 1.98 ( p=0.0002 ) vs 1.68 ( p=0.008 ) ) . BMD was also more strongly associated with biconcave deformities than either wedge or crush deformities and more so in men than in women . Severity of spinal osteophytosis was not associated with vertebral deformity . In conclusion , femoral neck BMD is at least equivalent to the lumbar spine BMD in strength of association with prevalent vertebral fractures . Spinal osteophytosis falsely elevates BMD without a concomitant decrease in fracture risk , indicating that any interpretation of spinal BMD needs to be adjusted for osteophytosis . These findings support the use of femoral neck bone densitometry in older men and women . Moreover , these data indicate that current criteria for radiological assessment of vertebral deformity are sufficiently loose to include a substantial proportion of non-fractures in the elderly , with important implication s for the design of clinical trials . However , irrespective of the criterion used , vertebral deformities in men are at least as common , if not more so , than in women , suggesting that vertebral osteoporotic fractures are overlooked in men OBJECTIVE Oral alendronate sodium is a potent , specific inhibitor of osteoclast-mediated bone resorption . To assess its efficacy and safety , a 3-year , r and omized , double-blind , multicenter study of 478 postmenopausal women with osteoporosis was conducted . PATIENTS AND METHODS Subjects received either placebo , alendronate 5 or 10 mg/day for 3 years , or 20 mg/day for 2 years followed by 5 mg/day for 1 year ( 20/5 mg ) . All subjects received 500 mg/day of supplemental calcium . Bone mineral density ( BMD ) was measured by dual energy x-ray absorptiometry ( DXA ) . RESULTS After 3 years , alendronate 10 mg induced marked increases in BMD of the lumbar spine ( 9.6 + /- 0.4 % ) , femoral neck ( 4.7 + /- 0.7 % ) and trochanter ( 7.4 + /- 0.6 % ) ( mean + /- SE ; each P < or = 0.001 ) versus decreases of 0.8 to 1.6 % with placebo . Progressive increases at these sites in the alendoronate 10 mg group were significant during both the second and third years . Alendronate 10 mg increased total body BMD ( 1.6 + /- 0.3 % , P < or = 0.001 ) , and prevented loss but did not increase BMD at the 1/3 forearm site . Alendronate 20/5 mg was no more effective , whereas alendronate 5 mg was significantly less effective than 10 mg at all sites . Bone turnover decreased to a stable nadir over 3 months for resorption markers ( urine deoxypyridinoline ) and over 6 months for formation markers ( alkaline phosphatase and osteocalcin ) . Mean loss of stature was reduced by 41 % in alendronate treated subjects ( P = 0.01 ) . CONCLUSION The safety profile of alendronate was similar to that of placebo . At 10 mg , there were no trends toward increased frequency of any adverse experience except for abdominal pain , which was usually mild , transient , and resolved with continued treatment . Thus , alendronate appears to be an important advance in the treatment of osteoporosis in postmenopausal women Objective To investigate the magnitude and pattern of the changes in bone mass during five years of continuous and cyclic sequential oestrogen/progestin treatment BACKGROUND Previous studies have shown that alendronate can increase bone mineral density ( BMD ) and prevent radiographically defined ( morphometric ) vertebral fractures . The Fracture Intervention Trial aim ed to investigate the effect of alendronate on the risk of morphometric as well as clinical ly evident fractures in postmenopausal women with low bone mass . METHODS Women aged 55 - 81 with low femoral-neck BMD were enrolled in two study groups based on presence or absence of an existing vertebral fracture . Results for women with at least one vertebral fracture at baseline are reported here . 2027 women were r and omly assigned placebo ( 1005 ) or alendronate ( 1022 ) and followed up for 36 months . The dose of alendronate ( initially 5 mg daily ) was increased ( to 10 mg daily ) at 24 months , with maintenance of the double blind . Lateral spine radiography was done at baseline and at 24 and 36 months . New vertebral fractures , the primary endpoint , were defined by morphometry as a decrease of 20 % ( and at least 4 mm ) in at least one vertebral height between the baseline and latest follow-up radiograph . Non-spine clinical fractures were confirmed by radiographic reports . New symptomatic vertebral fractures were based on self-report and confirmed by radiography . FINDINGS Follow-up radiographs were obtained for 1946 women ( 98 % of surviving participants ) . 78 ( 8.0 % ) of women in the alendronate group had one or more new morphometric vertebral fractures compared with 145 ( 15.0 % ) in the placebo group ( relative risk 0.53 [ 95 % Cl 0.41 - 0.68 ] ) . For clinical ly apparent vertebral fractures , the corresponding numbers were 23 ( 2.3 % ) alendronate and 50 ( 5.0 % ) placebo ( relative hazard 0.45 [ 0.27 - 0.72 ] ) . The risk of any clinical fracture , the main secondary endpoint , was lower in the alendronate than in the placebo group ( 139 [ 13.6 % ] vs 183 [ 18.2 % ] ; relative hazard 0.72 [ 0.58 - 0.90 ] ) . The relative hazards for hip fracture and wrist fracture for alendronate versus placebo were 0.49 ( 0.23 - 0.99 ) and 0.52 ( 0.31 - 0.87 ) . There was no significant difference between the groups in numbers of adverse experiences , including upper-gastrointestinal disorders . INTERPRETATION We conclude that among women with low bone mass and existing vertebral fractures , alendronate is well tolerated and substantially reduces the frequency of morphometric and clinical vertebral fractures , as well as other clinical fractures OBJECTIVE To study the efficacy of synthetic 1,25 dihydroxyvitamin D3 ( calcitriol ) in the treatment of osteoporosis . DESIGN Two-year , double-blind , r and omized clinical trial . SETTING University medical center . PATIENTS Fifty postmenopausal women with vertebral fractures recruited by referral . INTERVENTION Calcium intake was adjusted to 25 mmol/d ( 1000 mg/d ) at baseline . Patients were then r and omized to treatment with either calcitriol or placebo . During the study , calcium intake was reduced to 15 mmol/d ( 600 mg/d ) and the dose of calcitriol was adjusted to maintain serum calcium less than 2.74 mmol/L ( less than 11.0 mg/dL ) or urine calcium less than 9.96 mmol/d ( less than 400 mg/d ) . MEASUREMENTS AND MAIN RESULTS After 2 years , the mean dose of calcitriol in the treated group was 0.62 micrograms/d . Bone mineral density of the spine increased 1.94 % with calcitriol therapy and decreased 3.92 % with placebo ( P = 0.001 ) . Total body calcium increased 0.21 % with calcitriol therapy and decreased 1.85 % with placebo ( P = 0.004 ) . Patients receiving placebo had significant decreases in spine density ( P = 0.0007 ) and total body calcium ( P = 0.0004 ) . There were no differences in vertebral fracture rates between the groups . Renal function studies were not statistically different between the groups after 2 years . CONCLUSION The treatment of postmenopausal osteoporotic women with synthetic calcitriol for 2 years was associated with increases in spine density and total body calcium . No adverse effects on renal function were seen after long-term calcitriol therapy CONTEXT Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures , but its effects on fracture risk have not been studied for women without vertebral fractures . OBJECTIVE To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density ( BMD ) but no vertebral fractures . DESIGN R and omized , blinded , placebo-controlled trial . SETTING Eleven community-based clinical research centers . SUBJECTS Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less ( Hologic Inc , Waltham , Mass ) but no vertebral fracture ; 4432 were r and omized to alendronate or placebo and 4272 ( 96 % ) completed outcome measurements at the final visit ( an average of 4.2 years later ) . INTERVENTION All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol . Subjects were r and omly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial . MAIN OUTCOME MEASURES Clinical fractures confirmed by x-ray reports , new vertebral deformities detected by morphometric measurements on radiographs , and BMD measured by dual x-ray absorptiometry . RESULTS Alendronate increased BMD at all sites studied ( P<.001 ) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group , but not significantly so ( 14 % reduction ; relative hazard [ RH ] , 0.86 ; 95 % confidence interval [ CI ] , 0.73 - 1.01 ) . Alendronate reduced clinical fractures by 36 % in women with baseline osteoporosis at the femoral neck ( > 2.5 SDs below the normal young adult mean ; RH , 0.64 ; 95 % CI , 0.50 - 0.82 ; treatment-control difference , 6.5 % ; number needed to treat [ NNT ] , 15 ) , but there was no significant reduction among those with higher BMD ( RH , 1.08 ; 95 % CI , 0.87 - 1.35 ) . Alendronate decreased the risk of radiographic vertebral fractures by 44 % overall ( relative risk , 0.56 ; 95 % CI , 0.39 - 0.80 ; treatment-control difference , 1.7 % ; NNT , 60 ) . Alendronate did not increase the risk of gastrointestinal or other adverse effects . CONCLUSIONS In women with low BMD but without vertebral fractures , 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity . Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD CONTEXT Raloxifene hydrochloride , a selective estrogen receptor modulator , prevents bone loss in postmenopausal women , but whether it reduces fracture risk in these women is not known . OBJECTIVE To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures . DESIGN The Multiple Outcomes of Raloxifene Evaluation ( MORE ) study , a multicenter , r and omized , blinded , placebo-controlled trial . SETTING AND PARTICIPANTS A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis . The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events . INTERVENTIONS Participants were r and omized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills ; in addition , all women received supplemental calcium and cholecalciferol . MAIN OUTCOME MEASURES Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits . Nonvertebral fracture was ascertained by interview at 6-month-interim visits . Bone mineral density was determined annually by dual-energy x-ray absorptiometry . RESULTS At 36 months of the evaluable radiographs in 6828 women , 503 ( 7.4 % ) had at least 1 new vertebral fracture , including 10.1 % of women receiving placebo , 6.6 % of those receiving 60 mg/d of raloxifene , and 5.4 % of those receiving 120 mg/d of raloxifene . Risk of vertebral fracture was reduced in both study groups receiving raloxifene ( for 60-mg/d group : relative risk [ RR ] , 0.7 ; 95 % confidence interval [ CI ] , 0.5 - 0.8 ; for 120-mg/d group : RR , 0.5 ; 95 % CI , 0.4 - 0.7 ) . Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture . Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly ( RR , 0.9 ; 95 % CI , 0.8 - 1.1 for both raloxifene groups combined ) . Compared with placebo , raloxifene increased bone mineral density in the femoral neck by 2.1 % ( 60 mg ) and 2.4 % ( 120 mg ) and in the spine by 2.6 % ( 60 mg ) and 2.7 % ( 120 mg ) P<0.001 for all comparisons ) . Women receiving raloxifene had increased risk of venous thromboembolus vs placebo ( RR , 3.1 ; 95 % CI , 1.5 - 6.2 ) . Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer . CONCLUSIONS In postmenopausal women with osteoporosis , raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture STUDY OBJECTIVE To determine if calcitriol is an effective treatment in postmenopausal osteoporosis . DESIGN Double-blind , r and omized clinical trial of 2 years ' duration . SETTING University medical center with patients recruited by media announcements . PATIENTS Eighty-six postmenopausal women with vertebral compression fractures . INTERVENTIONS Patients were treated with calcitriol or placebo . Mean dose was 0.43 micrograms/d . Dietary calcium was 1000 mg/d ( 24.9 mmol/d ) . The medication dose and dietary calcium were adjusted for hypercalciuria or hypercalcemia . MEASUREMENTS AND MAIN RESULTS No significant differences between placebo and control groups were seen in the percent change in total body calcium ( 0.4 % + /- 1.0 compared with 0.0 % + /- 0.9 ) , single photon absorptiometry ( -0.5 % + /- 1.2 compared with -3.1 % + /- 0.9 ) or dual photon absorptiometry ( 0.0 % + /- 1.7 compared with -1.0 % + /- 2.2 ) . New fractures were seen in 16 % of the placebo group and 26 % of the calcitriol groups , so the difference in percent fractures was 10 % ( 95 % CI , -5.7 % to 25.7 % ) . Bone biopsies did not show changes in either group . The calcitriol group had significantly higher serum and urine calcium values , but renal function was not worse than in the placebo group . CONCLUSIONS Calcitriol is not an effective treatment for established postmenopausal osteoporosis OBJECTIVE To determine the relative risk for sustaining a first hip fracture after hormone replacement therapy . DESIGN Prospect i ve population -based cohort study with an average observation period of 5.7 years . SETTING A prescription-based cohort in the Uppsala health care region in Sweden . PARTICIPANTS The cohort ( 23 246 women ) comprised virtually all women of 35 years of age and older who received noncontraceptive estrogens from April 1977 through March 1980 . Comparisons were made with women in the background population . MEASUREMENTS Follow-up through 1983 was done with regard to hospital admissions for a first cervical or trochanteric hip fracture . The observed number of cases was compared with that expected on the basis of person-years of observation in the cohort and incidence rates in the background population . Analyses were made in exposure categories , based solely on prescription data . MAIN RESULTS During 133 022 person-years of observation , 163 cases of first hip fracture occurred , compared with the 205.5 expected , yielding an overall relative risk of 0.79 ( 95 % CI , 0.68 to 0.93 ) . The greatest protective effect ( relative risk , 0.37 ; CI , 0.13 to 0.79 ) was found against trochanteric fracture among women receiving potent estrogens who were under 60 years of age at cohort entry . This group also had the highest proportion of treatments with combinations of estrogens and progestogen ( 41 % ) . Treatment with less potent estrogens , mainly estriols , had no protective effect . Data indicated that the baseline risk for hip fracture was not lower in the cohort women than in the background population . CONCLUSIONS Treatment with potent estrogens , both alone and possibly when combined with progestogens , reduces the risk for both cervical and trochanteric hip fractures within the first decade after menopause As men age , their serum testosterone concentrations decrease , as do their bone densities . Because bone density is also low in hypogonadal men , we hypothesized that increasing the serum testosterone concentrations of men over 65 yr to those found in young men would increase their bone densities . We r and omized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch double blindly for 36 months . We measured bone mineral density by dual energy x-ray absorptiometry before and during treatment . Ninety-six men completed the entire 36-month protocol . The mean serum testosterone concentration in the men treated with testosterone increased from 367 + /- 79 ng/dL ( + /-SD ; 12.7 + /- 2.7 nmol/L ) before treatment to 625 + /- 249 ng/dL ( 21.7 + /- 8.6 nmol/L ; P < 0.001 ) at 6 months of treatment and remained at that level for the duration of the study . The mean bone mineral density of the lumbar spine increased ( P < 0.001 ) in both the placebo-treated ( 2.5 + /- 0.6 % ) and testosterone-treated ( 4.2 + /- 0.8 % ) groups , but the mean changes did not differ between the groups . Linear regression analysis , however , demonstrated that the lower the pretreatment serum testosterone concentration , the greater the effect of testosterone treatment on lumbar spine bone density from 0 - 36 months ( P = 0.02 ) . This analysis showed a minimal effect ( 0.9 + /- 1.0 % ) of testosterone treatment on bone mineral density for a pretreatment serum testosterone concentration of 400 ng/dL ( 13.9 nmol/L ) , but an increase of 5.9 + /- 2.2 % for a pretreatment testosterone concentration of 200 ng/dL ( 6.9 nmol/L ) . Increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men did not increase lumbar spine bone density overall , but did increase it in those men with low pretreatment serum testosterone concentrations The effects of 1α-hydroxyvitamin D3 [ 1α(OH)D3 ] on bone mineral density , fracture incidence , and bone metabolism were evaluated by a double-blind , placebo-controlled study . Eighty postmenopausal osteoporotic Japanese women ( 71.9±7.3 years , mean±SD ) were r and omly assigned to 1 μg of 1α(OH)D3 daily or inactive placebo for 1 year . All patients were given supplemental calcium ( 300 mg of elemental calcium daily ) . Lumbar ( L2–L4 ) bone mineral density ( BMD ) determined by dual energy X-ray absorptiometry increased 0.65 % with 1α(OH)D3 treatment and decreased 1.14 % with placebo ( P=0.037 ) . BMD in both the femoral neck and Ward 's triangle did not yield any significant differences between the two groups , whereas trochanter BMD in the 1α(OH)D3-treated group increased 4.20 % and decreased 2.37 % with placebo ( P=0.055 ) . X-ray analysis demonstrated that new vertebral fractures occurred in two patients with 1α(OH)D3 and in seven patients with placebo . The vertebral fracture rate in the treated group was significantly less ( 75/1000 patient years ) than in the control group ( 277/1000 patient years ; P=0.029 ) . Hypercalcemia ( 12.1 mg/100 ml ) occurred in one patient receiving 1α(OH)D3 ; however , the serum calcium level in this patient promptly decreased to the reference range after cessation of the treatment . There were no significant changes in serum creatinine level in either group . A significant increase in urinary excretion of calcium was found but there was no significant change in urinary excretion of hydroxyproline in the treated group . The serum level of bone-derived alkaline phosphatase activity significantly decreased by−26±26 ( mU/ml ) after the treatment ( P=0.003 ) . These results indicate that 1α(OH)D3 treatment is effective for maintaining trabecular bone mass and prevents further vertebral fractures without any serious adverse effects in postmenopausal osteoporosis BACKGROUND Many risk factors for hip fractures have been suggested but have not been evaluated in a comprehensive prospect i ve study . METHODS We assessed potential risk factors , including bone mass , in 9516 white women 65 years of age or older who had had no previous hip fracture . We then followed these women at 4-month intervals for an average of 4.1 years to determine the frequency of hip fracture . All reports of hip fractures were vali date d by review of x-ray films . RESULTS During the follow-up period , 192 women had first hip fractures not due to motor vehicle accidents . In multivariable age-adjusted analyses , a maternal history of hip fracture doubled the risk of hip fracture ( relative risk , 2.0 ; 95 percent confidence interval , 1.4 to 2.9 ) , and the increase in risk remained significant after adjustment for bone density . Women who had gained weight since the age of 25 had a lower risk . The risk was higher among women who had previous fractures of any type after the age of 50 , were tall at the age of 25 , rated their own health as fair or poor , had previous hyperthyroidism , had been treated with long-acting benzodiazepines or anticonvulsant drugs , ingested greater amounts of caffeine , or spent four hours a day or less on their feet . Examination findings associated with an increased risk included the inability to rise from a chair without using one 's arms , poor depth perception , poor contrast sensitivity , and tachycardia at rest . Low calcaneal bone density was also an independent risk factor . The incidence of hip fracture ranged from 1.1 ( 95 percent confidence interval , 0.5 to 1.6 ) per 1,000 woman-years among women with no more than two risk factors and normal calcaneal bone density for their age to 27 ( 95 percent confidence interval , 20 to 34 ) per 1,000 woman-years among those with five or more risk factors and bone density in the lowest third for their age . CONCLUSIONS Women with multiple risk factors and low bone density have an especially high risk of hip fracture . Maintaining body weight , walking for exercise , avoiding long-acting benzodiazepines , minimizing caffeine intake , and treating impaired visual function are among the steps that may decrease the risk OBJECTIVE To determine the relation between estrogen replacement therapy and fractures . DESIGN Prospect i ve cohort study . SETTING Four clinical centers in Baltimore County , Maryl and ; Minneapolis , Minnesota ; Portl and , Oregon ; and the Monongahela Valley , Pennsylvania . PARTICIPANTS 9704 ambulatory , nonblack women 65 years of age or older . MEASUREMENTS Estrogen use , medical history , and anthropometric data were obtained by question naire , interview , and examination . Appendicular bone mass was measured by single-photon absorptiometry . Incident fractures were vali date d by radiographic report . RESULTS After adjustment for potential confounders , current estrogen use was associated with a decrease in the risk for wrist fractures ( relative risk [ RR ] , 0.39 ; 95 % CI , 0.24 to 0.64 ) and for all nonspinal fractures ( RR , 0.66 ; CI , 0.54 to 0.80 ) when compared with no estrogen use . Results were similar for women using unopposed estrogen or estrogen plus progestin , for women younger or older than 75 years of age , and for current smokers or nonsmokers . The effect of estrogen remained after adjustment was made for appendicular bone mass . The relative risk for hip fracture tended to be lower among current users ( RR , 0.60 ; CI , 0.36 to 1.02 ) than among never-users . Estrogen was most effective in preventing hip fracture among those older than 75 years . Current users who started estrogen within 5 years of menopause had a decreased risk for hip fractures ( RR , 0.29 ; CI , 0.09 to 0.92 ) , wrist fractures ( RR , 0.29 ; CI , 0.13 to 0.68 ) , and all nonspinal fractures ( RR , 0.50 ; CI , 0.36 to 0.70 ) when compared with women who had never used estrogen . Previous use of estrogen for more than 10 years or use begun soon after menopause had no substantial effect on the risk for fractures . CONCLUSIONS Current use of estrogen appears to decrease the risk for fracture in older women . These results suggest that for protection against fractures , estrogen should be initiated soon after menopause and continued indefinitely CONTEXT Risedronate , a potent bisphosphonate , has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but , to our knowledge , it has not been evaluated in the treatment of established postmenopausal osteoporosis . OBJECTIVE To test the efficacy and safety of daily treatment with risedronate to reduce the risk of vertebral and other fractures in postmenopausal women with established osteoporosis . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline who were enrolled at 1 of 110 centers in North America conducted between December 1993 and January 1998 . INTERVENTIONS Subjects were r and omly assigned to receive oral treatment for 3 years with risedronate ( 2.5 or 5 mg/d ) or placebo . All subjects received calcium , 1000 mg/d . Vitamin D ( cholecalciferol , up to 500 IU/d ) was provided if baseline levels of 25-hydroxyvitamin D were low . MAIN OUTCOME MEASURES Incidence of new vertebral fractures as detected by quantitative and semiquantitative assessment s of radiographs ; incidence of radiographically confirmed nonvertebral fractures and change from baseline in bone mineral density as determined by dual x-ray absorptiometry . RESULTS The 2.5 mg/d of risedronate arm was discontinued after 1 year ; in the placebo and 5 mg/d of risedronate arms , 450 and 489 subjects , respectively , completed all 3 years of the trial . Treatment with 5 mg/d of risedronate , compared with placebo , decreased the cumulative incidence of new vertebral fractures by 41 % ( 95 % confidence interval [ CI ] , 18%-58 % ) over 3 years ( 11.3 % vs 16.3 % ; P= .003 ) . A fracture reduction of 65 % ( 95 % CI , 38%-81 % ) was observed after the first year ( 2.4 % vs 6.4 % ; P<.001 ) . The cumulative incidence of nonvertebral fractures over 3 years was reduced by 39 % ( 95 % CI , 6%-61 % ) ( 5.2 % vs 8.4 % ; P = .02 ) . Bone mineral density increased significantly compared with placebo at the lumbar spine ( 5.4 % vs 1.1 % ) , femoral neck ( 1.6 % vs -1.2 % ) , femoral trochanter ( 3.3 % vs -0.7 % ) , and midshaft of the radius ( 0.2 % vs -1.4 % ) . Bone formed during risedronate treatment was histologically normal . The overall safety profile of risedronate , including gastrointestinal safety , was similar to that of placebo . CONCLUSIONS These data suggest that risedronate therapy is effective and well tolerated in the treatment of women with established postmenopausal osteoporosis In a prospect i ve , r and omized study , 66 osteoporotic postmenopausal women ( mean age , 67 years ) were scheduled to receive either alfacalcidol 0.25 microgram twice daily together with calcium 500 mg twice daily ( treatment group , n = 24 ) or placebo twice daily with calcium 500 mg twice daily ( control group , n = 42 ) for three years . In the treatment group , bone mineral content at the distal radius may have increased by 2 % compared to a significant decrease of 7.8 % in the control group . The difference between the two groups was also significant . Since the dose of alfacalcidol and calcium remained unadjusted , frequent hypercalciuria , as well as occasional mild , transient elevations of serum calcium , were observed in the treatment group . No changes in serum creatinine levels or creatinine clearance throughout the study were observed . The two groups did not differ with respect to the frequency of clinical side effects , which were mainly gastrointestinal and probably related to the calcium supplementation . Alfacalcidol and calcium may prevent further bone loss in women suffering from postmenopausal osteoporosis 50 Japanese women within 10 years after menopause ( mean age 52.5 years ) were studied to determine the effects of 0.75 microgram of 1-alpha-hydroxyvitamin D3 [ 1-alpha-(OH)D3 ] with calcium ( 150 mg/day ) ( treated group : N = 25 ) and calcium only ( control group : N = 25 ) for 12 months on bone mass and metabolism . Their L2 - 4 BMD measurements were 1.5 SD below the mean value of Japanese young , normal women . L2 - 4 BMDs increased significantly in the treated group ( + 2.1 % ; p < 0.01 ) , but decreased significantly in controls ( -2.1 % ; p < 0.01 ) . Although serum calcium and creatinine remained unchanged in both groups , phosphorus levels increased significantly in the treated group ( p < 0.01 ) . Urinary calcium/creatinine ( Cr ) increased in both groups . Urinary pyridinoline/Cr and deoxypyridinoline/Cr decreased significantly in the treated group ( p < 0.05 ) , but not in the control group . Serum osteocalcin levels remained unchanged in both groups . Intact parathyroid hormone levels decreased significantly ( p < 0.05 ) and calcitonin levels significantly increased in the treated group ( p < 0.05 ) , but these changes were not observed in the control group . These data clearly demonstrate that 0.75 microgram of 1-alpha-(OH)D3 maintained bone mass by reducing bone resorption by modulation of calcium-regulating hormones . Temporarily increased urinary calcium excretion was observed in control group , but did not appear to be effective in modulating bone turnover OBJECTIVE To evaluate the effects of 120 weeks of intermittent cyclical etidronate on the progression of bone loss and fracture incidence and rate in postmenopausal osteoporotic women after 150 weeks of either etidronate or placebo treatment . METHODS This was an open label followup study of 37 postmenopausal osteoporotic women enrolled from the earlier 150 week study , 17 from the etidronate group and 20 from the placebo group . Treatment cycles were of oral doses of etidronate 400 mg/day for 2 weeks , followed by a 13 week drug-free period for a total of 120 weeks . All patients received a daily supplement of 0.5 g calcium and 400 U vitamin D. RESULTS During the earlier 150 week study , mean vertebral bone mineral content increased significantly in the etidronate group by 5.5 % ( p = 0.013 ) and decreased by 2.7 % ( not significant ) in the placebo group . After 120 weeks of etidronate treatment in this followup study , patients who had formerly received etidronate experienced an additional 1.4 % increase ; after 5 years , bone mineral content was 6.9 % above the original baseline ( p = 0.037 ) . Bone mineral content also increased in the former placebo group during the latter study , up to 5.3 % above the original study baseline ( not significant ) . The vertebral fracture rate in the former placebo group decreased significantly , from 103 to 27 per 100 patient-years ( p < 0.01 ) , while the fracture rate in the former etidronate group was unchanged ( 38 and 33 per 100 patient-years ) . CONCLUSION Five years of etidronate therapy for postmenopausal osteoporosis results in significant increases in vertebral bone mineral content , and the previously observed reduction in vertebral fracture rate in the etidronate group is maintained during at least 5 years of therapy The separate and combined effects of weight-bearing exercise and hormone replacement therapy ( HRT ) on bone mineral density ( BMD ) were studied in 32 women , 60 to 72 years of age . HRT consisted of continuous conjugated estrogens 0.625 mg/day and trimonthly medroxyprogesterone acetate 5 mg/day for 13 days . Exercise consisted of 2 months of low-intensity exercise followed by 9 months of more vigorous weight-bearing exercise approximately 45 minutes/day , > or = 3 days/week , at 65 - 85 % of maximal heart rate . Lumbar spine and proximal femur BMD were significantly increased in response to exercise and to HRT , and total body BMD was significantly increased in response to HRT ; neither exercise nor HRT had an effect on wrist BMD . The combination of exercise + HRT result ed in increased BMD at all sites except the wrist , with effects being additive for the lumbar spine and Ward 's triangle and synergistic for the total body . Based on reductions in serum osteocalcin levels , it appears that increases in BMD in response to HRT and exercise + HRT were due to decreased bone turnover . The lack of change in serum osteocalcin and IGF-I in response to exercise alone suggests that increases in BMD were due to decreased bone resorption and not increased formation . Results indicate that weight-bearing exercise + HRT may be effective in preventing and /or treating osteoporosis . It is likely that the additive effects of weight-bearing exercise and HRT on bone mineral accretion , coupled with other adaptations to the exercise ( i.e. , increased strength and functional capacity ) , could effectively reduce the incidence of falls and osteoporotic fractures As part of a prospect i ve study begun in 1981 , we evaluated 8,600 postmenopausal women and 5,049 men residing in a southern California retirement community for risk factors for hip fracture . Incidence rates were twice as high in women as in men , but in both sexes the rates nearly doubled every 5 years between 70 and 90 years . Active exercise was strongly and negatively associated with hip fracture risk in both sexes ; the age-adjusted relative risk was 0.6 and 0.5 for females and males , respectively , for 1 or more hours of exercise per day compared with less than 1/2 hour of exercise . A high body mass index ( upper tertile of weight divided by height squared ) was associated with a strong reduction in hip fracture risk for females ( RR = 0.5 ) . Current cigarette smokers had a significantly increased risk ( RR = 1.8 and RR = 2.2 for females and males , respectively ) compared with never-smokers , but the risk for past smokers was not different from that of lifetime nonsmokers . Other factors related to reduced hip fracture risk in women were high parity , late age at menarche , and long menstrual cycle length . These age-adjusted relative risk estimates did not change material ly in multivariate analysis when adjusted simultaneously for age , active exercise , body mass , smoking , and , for women , age at menarche and number of children . Among estrogen users , the lowest risk of hip fracture was observed for recent users ( RR = 0.8 ) , while users who had stopped estrogen use 15 or more years ago had a relative risk of 1.1 , suggesting that the protective effect of estrogen dissipates after many years since cessation of estrogen Twenty-eight women with postmenopausal osteoporosis were studied in a double-blind trial aim ed to compare the effects of a one-year treatment with 1,25-dihydroxyvitamin D3 ( 1,25(OH)2D3 ) , estradiol valerate ( E2 ) and placebo . Patients were divided into 4 groups : group 1 was given 1,25(OH)2D3 alone , group 2 was given E2 alone , group 3 was given 1,25(OH)2D3 + E2 , group 4 received a placebo . The evaluation of the effects of the treatments included clinical examination of patients , the measurement of a number of biochemical parameters , such as plasma and urinary calcium and phosphate , urinary hydroxyproline , serum alkaline phosphatase , the measurement of intestinal calcium absorption and bone mineral content ( BMC ) and a histomorphometric study of bone biopsies from the iliac crest . The best clinical results were obtained in the patients who were given 1,25(OH)2D3 alone ; appreciable results were also noticed in the patients who were given E2 alone or in combination with 1,25(OH)2D3 , while patients in the placebo group worsened . BMC decreased in the placebo group and increased , although non significantly , in the patients treated with 1,25(OH)2D3 or E2 or both . The histomorphometric study showed a significant increase in the mean trabecular diameter in patients treated with 1,25(OH)2D3 alone or in combination with E2 . Changes in the volume density of trabecular bone paralleled those in BMC . The results of the trial indicate that 1,25(OH)2D3 is an effective therapeutic agent in postmenopausal osteoporosis The value of a program for the rehabilitation of osteoporotic patients ( PRO ) was assessed from a 4-year follow up of 139 patients referred to the program over its initial 2 years of operation . The program consisted of educational seminars , social activities and regular exercise supervision . Patients had annual clinical assessment s , and bone mass measurements by neutron activation analysis ( reported as CaBI ) . Fitness was assessed by performance on a treadmill ( reported in terms of VO2 max , ml/kg/min).Seventy-eight of the 139 patients remained in the program over the 4-year follow-up . This unusually high level of commitment to the program is indicative of the psychological value that patients have derived from it . The effect of the program on the osteoporosis process was inconclusive . Group 2 , the 37 patients who obtained the greatest improvement in fitness ( VO2max > 6 ml/kg/min ) , had a significantly greater reduction in back pain than did group 1 , the 36 with less significant improvement ( VO2max > 6 ml/kg/min ) . The bone mass and incidence of vertebral fractures on entry into the program were not significantly different between the two groups . Group 2 had on average a greater increase in bone mass over the 4 years ; mean increases in CaBI , ( ±SD ) were 0.09±0.09 and 0.05±0.10 for groups 2 and 1 respectively . Group 2 had on average fewer new vertebral fractures ( 0.08±0.36 and 0.28±0.75 for groups 2 and 1 respectively ) . While these findings were encouraging , they did not reach significance at the 5 % level ( p=0.075 and p=0.09 for changes in CaBI and new vertebral fractures , respectively ) . A large r and omized study would be required to establish clinical value quantitatively . Nevertheless , the qualitative benefit to patients is sufficiently impressive for a wider experience in rehabilitation programs to be encouraged The purpose of this open , prospect i ve , controlled , r and omized trial was to study the effect of intermittent , cyclic etidronate on the bone mass of osteoporotic postmenopausal women with or without fractures . Eligible subjects were asymptomatic women less than 75 years old who had been amenorrhoeic for at least 1 year . Those with secondary osteoporosis were excluded . Subjects also had to be ambulant with a bone mineral density ( BMD ) of the lumbar spine > 1 SD below that of age matched controls ( Z-score < −1 SD ) . Eighty patients were enrolled , of whom 65 were recruited through a screening programme conducted in the practice s of two general practitioners . The remaining patients were from other referrals . The subjects were r and omized to two groups of 40 women . Treatment regimens were as follows . The etidronate group was treated with etidronate 400 mg once daily for 14 days followed by 76 days of 500 mg of elementary calcium once daily ; this cycle was repeated every 3 months . The calcium group took 500 mg of elementary calcium once daily . The groups were not different in age , height , weight , time since menopause , BMD at baseline and prevalent vertebral fractures . In 50 patients ( 28 in the etidronate group and 22 in the calcium group ) no vertebral fractures were present ( 67 % ) . Sixty-four patients ( 35 in the etidronate group and 29 in the calcium group ) completed the 3 years of the study . In the etidronate group the mean BMD of the lumbar spine , femoral neck , trochanter and Ward 's triangle increased by 5.7 % , 1.4 % , 7.1 % and 10.9 % from baseline values respectively ( p<0.05 at all sites except for the femoral neck ) . In the calcium group no significant changes from baseline were found at any time point at any site after 3 years , except for the femoral neck , where BMD at 156 weeks decreased significantly by 3 % ( p<0.003 ) . In 3 patients , all in the calcium group , six new fractures were found . There were no serious adverse effects . We conclude that intermittent , cyclic treatment with etidronate causes a significant increase in the BMD of the lumbar spine and the proximal femur in osteopenic postmenopausal women , and that treatment is safe and has no serious adverse effects Vitamin D deficiency is common in elderly persons , especially those with hip fracture [ 1 , 2 ] . It is caused by low exposure to sunshine , decreased synthesis of vitamin D3 in the aging skin , and a diet low in vitamin D [ 3 , 4 ] . The mean vitamin D intake in elderly persons in the Netherl and s is about 100 IU/d , half that of elderly persons in the United States [ 5 ] . Most of this vitamin D comes from margarine , which is the only vitamin D-supplemented food in the Netherl and s ( 3 IU/g ) . In vitamin D deficiency , the low serum concentration of 25-hydroxyvitamin D [ 25(OH)D ] leads to a low 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] concentration and then to a higher serum parathyroid hormone concentration , especially in the winter [ 6 - 10 ] . Histologically , the increased parathyroid activity is associated with high bone turnover , leading to cortical bone loss and low density bone [ 5 , 11 ] , which may lead to hip fracture . We previously studied the effects of vitamin D supplementation in residents of a home for the elderly and residents of a nursing home [ 10 ] . Vitamin D3 , 400 IU/d , led to an adequate increase of the serum 25(OH)D concentration , to a small but significant increase of the serum 1,25(OH)2D concentration , and to a decrease of the serum concentration of intact parathyroid hormone . It was recently observed [ 12 , 13 ] that bone mineral density at the hip is positively related to serum 25(OH)D concentration in postmenopausal and elderly women . Therefore , it might be expected that vitamin D supplementation would increase bone mineral density in elderly persons deficient in vitamin D. In line with this expectation , it was shown that vitamin D supplementation prevented bone loss from the spine during the winter in postmenopausal women [ 14 ] . These results suggest that vitamin D supplementation may reduce the incidence of hip fractures , because bone strength shows a strong correlation with bone mineral density [ 15 ] . However , increasing bone mineral density through a therapeutic intervention does not necessarily lead to increased bone strength , as has been shown with sodium fluoride [ 16 ] . Bone structure and bone quality are also determinants of bone strength [ 17 ] , and falls are a risk factor for hip fractures [ 18 ] . Therefore , hip fracture should be the outcome criterion in studies on the effect of vitamin D supplementation . Intervention studies on the prevention of osteoporotic fractures necessitate large numbers of patients , because the outcome has an annual incidence of 0.5 % to 4 % in the elderly population [ 19 ] . We report the results of a large-scale , prospect i ve study on the effect of vitamin D supplementation on the incidence of hip and other osteoporotic fractures . Methods Participants The study included 2578 persons ( 1916 women and 662 men ) 70 years of age and older ( mean age SD , 80 6 years ; range , 70 to 97 years ) . Participants were recruited from general practitioners , from apartment houses for elderly persons , and from homes for elderly persons in Amsterdam and its vicinity . Persons recruited from practitioners were living independently ; those recruited from apartment houses and homes were receiving some care , but less than they would have received in a nursing home . Participants had to be reasonably healthy and able to give informed consent . Persons with a history of hip fracture or total hip arthroplasty , known hypercalcemia , sarcoidosis , or recent urolithiasis ( < 5 years earlier ) were excluded . Patients who had diseases or who used medications that influence bone metabolism ( such as thyroid disease or glucocorticoid medication ) were not excluded . The spontaneous use of vitamin D supplements and multivitamins was discouraged , but the prescription practice s of the general practitioners were not altered . All vitamin use was carefully documented . The study was approved by the Ethical Review Board of the Vrije Universiteit Hospital , and all participants gave informed consent . Study Design After checking the inclusion and exclusion criteria and obtaining informed consent , the participants were r and omly assigned to receive either active treatment with vitamin D3 or placebo . The study was double-blind , and r and omization was done in blocks of 10 per general practice , apartment house , or home . R and omization lists were made using a computerized r and om-number generator . Lists in sealed envelopes were sent to the hospital pharmacy for assignment . Each participant took either one tablet per day that contained vitamin D3 , 400 IU , or one placebo tablet per day that was identical in appearance and taste to the vitamin tablet . After enrollment , the participants received the first container of tablets ( 210 tablets ) . The container was replaced every 6 months with a full container . All participants were also advised in writing to consume at least three servings of dairy products per day ( for example , 1 glass of milk , 1 cup of yogurt , and 1 slice of cheese ) to ensure a calcium intake of at least 800 to 1000 mg/d . The study was started in August 1988 . The last participant was enrolled in December 1990 , and all participants had stopped using study medication by December 1993 . The follow-up period had been planned to last no more than 3 years , but because the number of hip fractures during the study was lower than expected , a 6-month extension was planned . The study participants thus received medication for 3 to 3.5 years ; those who received it for 3.5 years were those who consented to the 6-month extension . Total follow-up was to a maximum of 4 years . Data collected at baseline included an outdoor activity score ( 1 equals going outdoors less than once a week ; 2 equals going outdoors 1 or 2 times per week ; and 3 equals going outdoors 3 times per week or more ) and a score for sunshine exposure ( when outside : 1 equals in the shade as much as possible ; 2 equals sometimes in sunshine ; 3 equals much exposure to sunshine ) . These scores show a positive relation with serum 25(OH)D concentration [ 3 ] . Mobility was estimated by a walking score that ranged from 1 ( unable to walk ) to 5 ( walks independently a fair distance on any surface ) [ 20 ] . The dietary calcium intake from dairy products was estimated in a subset of 348 women by using a question naire , as described previously [ 21 ] . The participants were evaluated annually with a question naire on hip fractures , other peripheral fractures , outdoor score , sunshine exposure score , use of vitamin supplements , and walking score . Each general practitioner or caretaker was asked to immediately report change of address , hip fracture , or death . Hip fracture and death were verified by the general practitioner . All participants were followed for the maximal period of 4 years if possible , even if they had stopped using the trial medication , had sustained a fracture , or had moved to another city . To investigate possible selection bias , 267 potential participants in a home for the elderly and its adjunct apartments ( all residents of the institution ) were studied for baseline characteristics , including age , sex , sunshine exposure score , outdoor score , walking score , and reasons for nonparticipation . Compliance was checked when the tablet containers were replaced ( every 6 months ) , by question naire ( every year ) , and by measurement of the serum 25(OH)D concentration . Serum 25(OH)D concentration was measured at baseline and after 1 year in 270 persons who participated in a sub study investigating the effect of vitamin D supplementation on bone mineral density and bone turnover variables . This sub study included a nonr and om sample of participants from several apartment houses and homes for the elderly and is described in detail elsewhere [ 21 ] . In the same sub study , dietary calcium intake from diary products was assessed . Serum 25(OH)D concentration was also estimated during the third year of the study in February and March in a r and om sample of 96 participants drawn from the remaining study population . These participants received a letter giving them an appointment within 10 days ; the blood sample s were drawn at home . Serum 25(OH)D concentration was measured by competitive protein binding assay after being purified by gradient high-pressure liquid chromatography . The intra- and interassay coefficients of variation were 5 % and 6 % , respectively [ 22 ] . Statistical Analysis Baseline data of the vitamin D group and the placebo group were compared using t-tests ( age , calcium intake ) , chi-square tests ( sex , residence ) , and Wilcoxon rank-sum tests ( scores ) . The serum 25(OH)D concentrations of both groups were compared using t-tests . Data on fractures and mortality were analyzed by survival analysis using log-rank tests , Cox proportional-hazards regression , and hazard rate ratios [ 23 ] . Hip fractures are presented using the Kaplan-Meier method . All participants were kept in the study as long as possible . The data were analyzed in two ways . The intention-to-treat analysis included all r and omly assigned participants for either the total follow-up period or until fracture , death , or loss to follow-up . The active treatment analysis included the participants as long as they stated that they were using the trial medication . Thus , the participants were included in the active treatment analysis until they stopped using the trial medication , regardless of whether a fracture occurred after they had stopped . Age , sex , and residence were added in both analyses as covariates to the Cox regression model . Because outdoor score , sunshine score , and walking score were interrelated ( correlation coefficients ranging from 0.21 to 0.59 ) and were likely to indicate general health or mobility , they were averaged over the years and added up to a sum score . For this purpose , the walking score was simplified ( 1 , 2 , or 3 equals 1 ; 4 equals 2 ; 5 equals 3 ) , because the lower walking scores applied to a few participants only . The result ing total score , ranging from 3 to 9 , was entered as a covariate in the model . The level of compliance ( weekly intake as reported on A two-year double-blind study monitored and evaluated the effects of 1 alpha-hydroxy vitamin D3 ( 1 alpha(OH)D3 ) on the lumbar ( L2 - 4BMD ) and total body bone mineral densities ( TBBMD ) and occurrence of fracture in 113 female osteoporotic patients receiving 0.75 micrograms/day of 1 alpha(OH)D3 ( n = 57 ) or a placebo ( n = 56 ) with calcium supplementation in both groups . L2 - 4BMD increased 1.81.% and 2.32 % after one and 2 years in the 1 alpha (OH)D3 group , but decreased 1.89 % ( P < 0.05 ) and 0.28 % in the placebo group . A significant difference ( P < 0.01 ) existed between the two groups after one year . TBBMD decreased significantly in the placebo group by 3.34 % ( P < 0.01 ) and 3.52 % after one and 2 years . Six new fractures occurred in the control group , but only two in the 1 alpha(OH)D3 group ( Odd 's ratio = 0.343 , 95 % confidence range ; 0.0648 - 1.815 ) . There were no serious adverse effects of the 1 alpha(OH)D3 treatment . It was concluded that two-year treatment with 1 alpha(OH)D3 increased the lumbar BMD and inhibited the decrease in TBBMD . Although it was not significant , new fracture occurrence in the 1 alpha(OH)D3 group was around 1/3 of that in the control group BACKGROUND The use of calcium supplements slows bone loss in the forearm and has a beneficial effect on the axial bone density of women in late menopause whose calcium intake is less than 400 mg per day . However , the effect of a calcium supplement of 1000 mg per day on the axial bone density of postmenopausal women with higher calcium intakes is not known . METHODS We studied 122 normal women at least three years after they had reached menopause who had a mean dietary calcium intake of 750 mg per day . The women were r and omly assigned to treatment with either calcium ( 1000 mg per day ) or placebo for two years . The bone mineral density of the total body , lumbar spine , and proximal femur was measured every six months by dual-energy x-ray absorptiometry . Serum and urine indexes of calcium metabolism were measured at base line and after 3 , 12 , and 24 months . RESULTS The mean ( + /- SE ) rate of loss of total-body bone mineral density was reduced by 43 percent in the calcium group ( -0.0055 + /- 0.0010 g per square centimeter per year ) as compared with the placebo group ( -0.0097 + /- 0.0010 g per square centimeter per year , P = 0.005 ) . The rate of loss of bone mineral density was reduced by 35 percent in the legs ( P = 0.02 ) , and loss was eliminated in the trunk ( P = 0.04 ) . Calcium use was of significant benefit in the lumbar spine ( P = 0.04 ) , and in Ward 's triangle the rate of loss was reduced by 67 percent ( P = 0.04 ) . Calcium supplementation had a similar effect whether dietary calcium intake was above or below the mean value for the group . Serum parathyroid hormone concentrations tended to be lower in the calcium group , as were urinary hydroxyproline excretion and serum alkaline phosphatase concentrations . CONCLUSIONS Calcium supplementation significantly slowed axial and appendicular bone loss in normal post-menopausal women PURPOSE To determine whether intermittent cyclical etidronate therapy can prevent early postmenopausal bone loss . PATIENTS AND METHOD This was a 2-year outpatient , r and omized , double-blind , placebo-controlled clinical trial . The subjects were 152 women within 1 to 10 years of the onset of menopause and bone mineral density ( BMD ) between 0 and -2 SD of normal values for a 50 year old woman . The women were stratified according to years since the menopause ( 1 to 3 years : n = 43 ; 4 to 6 years : n = 53 ; 7 to 10 years : n = 56 ) . Measurements of lumbar spine , proximal femur and total body BMD were performed at baseline , 12 and 24 months by dual x-ray absorptiometry . Biochemical markers of bone resorption and bone formation were measured on the same visits . RESULTS One hundred thirty-five subjects completed the study . Mean percentage change in lumbar spine BMD ( and SEM ) at 2 years was + 2.14 (0.47)% in the etidronate group and -1.72 (0.41)% in the placebo group . Results for lumbar spine BMD in the treated and control groups stratified according to years since the menopause were : 1 to 3 years : + 1.73 (0.84)% and -3.30 (0.70)% ; 4 to 6 years : + 1.37 (0.88)% and -1.80 (0.61)% ; 7 to 10 years : + 3.42 (0.61)% and -0.38 (0.70)% . The effect of both treatment group and menopausal stratum were highly statistically significant for lumbar spine and total body BMD . Treatment group , but not stratum , was significant for BMD in the proximal femur . Markers of bone resorption and bone formation were significantly decreased by etidronate therapy . CONCLUSIONS Cyclical etidronate prevents bone loss in the total skeleton and at the clinical ly relevant sites ( spine and proximal femur ) even in the early postmenopausal years . Hence , it appears to be an effective and safe nonhormonal therapy in postmenopausal women with normal or low BMD CONTEXT Observational studies have found lower rates of coronary heart disease ( CHD ) in postmenopausal women who take estrogen than in women who do not , but this potential benefit has not been confirmed in clinical trials . OBJECTIVE To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease . DESIGN R and omized , blinded , placebo-controlled secondary prevention trial . SETTING Outpatient and community setting s at 20 US clinical centers . PARTICIPANTS A total of 2763 women with coronary disease , younger than 80 years , and postmenopausal with an intact uterus . Mean age was 66.7 years . INTERVENTION Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily ( n = 1380 ) or a placebo of identical appearance ( n = 1383 ) . Follow-up averaged 4.1 years ; 82 % of those assigned to hormone treatment were taking it at the end of 1 year , and 75 % at the end of 3 years . MAIN OUTCOME MEASURES The primary outcome was the occurrence of nonfatal myocardial infa rct ion ( MI ) or CHD death . Secondary cardiovascular outcomes included coronary revascularization , unstable angina , congestive heart failure , resuscitated cardiac arrest , stroke or transient ischemic attack , and peripheral arterial disease . All-cause mortality was also considered . RESULTS Overall , there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes : 172 women in the hormone group and 176 women in the placebo group had MI or CHD death ( relative hazard [ RH ] , 0.99 ; 95 % confidence interval [ CI ] , 0.80 - 1.22 ) . The lack of an overall effect occurred despite a net 11 % lower low-density lipoprotein cholesterol level and 10 % higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group ( each P<.001 ) . Within the overall null effect , there was a statistically significant time trend , with more CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5 . More women in the hormone group than in the placebo group experienced venous thromboembolic events ( 34 vs 12 ; RH , 2.89 ; 95 % CI , 1.50 - 5.58 ) and gallbladder disease ( 84 vs 62 ; RH , 1.38 ; 95 % CI , 1.00 - 1.92 ) . There were no significant differences in several other end points for which power was limited , including fracture , cancer , and total mortality ( 131 vs 123 deaths ; RH , 1.08 ; 95 % CI , 0.84 - 1.38 ) . CONCLUSIONS During an average follow-up of 4.1 years , treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease . The treatment did increase the rate of thromboembolic events and gallbladder disease . Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events , we do not recommend starting this treatment for the purpose of secondary prevention of CHD . However , given the favorable pattern of CHD events after several years of therapy , it could be appropriate for women already receiving this treatment to continue Fractures are an important cause of disability in elderly women , especially among those with osteopenia . Decreased bone mass increases the risk for most types of fractures [ 1 - 4 ] . In particular , we recently reported [ 5 ] that most fractures in elderly women are associated with low bone mass at appendicular sites ( the radius and calcaneus ) . The risk for these fractures , including some fractures not previously linked to osteopenia , such as of the leg and h and , increased 40 % to 80 % for each st and ard deviation reduction in appendicular bone mass [ 5 ] . We also found that appendicular bone mass predicts the risk for all nonspine fractures as well as for bone mass measured at the hip and spine [ 6 ] . Despite the strong relation between appendicular bone mass and risk for fracture , little consensus exists about the many proposed risk factors for decreased bone mass [ 7 , 8 ] , perhaps because most studies have examined a limited number of risk factors in relatively small selected cohorts . To determine what factors might contribute to osteopenia in older women , we examined a wide variety of potential correlates of appendicular bone mass in the Study of Osteoporotic Fractures , a large multicenter , community-based study of elderly women . Methods Patients From September 1986 to October 1988 , women who were at least 65 years old were recruited in four areas of the United States : Portl and , Oregon ; Minneapolis , Minnesota ; Baltimore , Maryl and ; and the Monongahela Valley near Pittsburgh , Pennsylvania . Age-eligible women were identified from membership lists from several sources , as previously reported [ 1 ] . We excluded black women because of the reduced incidence of hip fractures in this group [ 9 ] , and we excluded women who were unable to walk without the assistance of another person or who had bilateral hip replacements . Measurement of Bone Mass Bone mass ( in g/cm2 ) was measured using OsteoAnalyzers ( Siemens-Osteon , Wahiawa , Hawaii ) . We scanned three sites : the distal radius , the midradius , and the calcaneus . The protocol for the bone mass measurements has been described elsewhere [ 1 ] . To describe the reproducibility of these measurements , a participant in the study was measured five times on 5 consecutive days at each of the four clinical centers . The average coefficients of variation in these older women ( st and ard deviation/mean for each subject ) were 1.5 % for the distal radius , 2.0 % for the midradius , and 1.3 % for the calcaneus . To assess variations between scanners at the four centers , two investigators were measured by all four machines ; the mean of their coefficients of variation in these younger subjects was 0.4 % for the distal radius , 0.5 % for the midradius , and 1.2 % for the calcaneus [ 10 ] . The correlation coefficients between the measurement sites were distal and midradius , 0.75 ; calcaneus and distal radius , 0.66 ; and calcaneus and midradius , 0.63 . Predictor Variables Participants completed a self-administered question naire and were interviewed and examined at the clinical center . A selected medical history was obtained , including a history of a physician diagnosis of osteoporosis , spine fracture , arthritis , gastric surgery , hyperthyroidism , and stroke . Reproductive history , including age of last menstrual period , genitourinary surgery ( hysterectomy , oophorectomy ) , number of pregnancies , and breast-feeding , was recorded . Previous fractures in subjects and their parents or sisters were noted . We collected detailed records about specific health habits including lifetime smoking history , alcohol use , and caffeine intake . Women who had smoked less than 100 cigarettes in their lifetime were considered nonsmokers . We assumed that a cup of coffee contained 95 mg of caffeine and that tea and cola drinks contained 55 mg and 45 mg , respectively . Participants were asked to bring all prescription and nonprescription medications with them to the interview for verification . The dose and duration of use of sex hormones , diuretics , corticosteroids , thyroid supplements , aluminum-containing antacids , vitamin D , sedative hypnotics , and antiepileptic medications were obtained . The frequency and duration of use of calcium supplements were recorded ; use of TUMS ( which can be taken as an antacid or calcium supplement ) was recorded separately . Responses to the question naire were checked by a trained interviewer and were verified against the labels of medications that the subject brought to the interview . Recent dietary history ( past 12 months ) , particularly calcium , phosphorus , and protein intake , was assessed by a checklist-interview method developed from the HANES-II survey [ 11 ] . Food models were used to estimate portion sizes , and foods that account for 80 % of calcium intake in most adults were included . This instrument has a correlation of 0.76 with calcium intake assessed by a 7-day diet diary , but it tends to underestimate calcium intake by approximately 150 mg/day [ 12 ] . The frequency of milk consumption as a child and young adult was also assessed by question naire . Physical activity was examined with a modified Paffenbarger survey that has been vali date d in postmenopausal women [ 13 - 16 ] . The type and duration of weight-bearing recreational activities from the previous 12 months were recorded , and these were converted into weekly caloric expenditure . Other current activities , such as stair climbing , walking , and heavy household chores , were included . Intensity-weighted measures were calculated by design ating activities as low ( for example , walking or gardening ) , medium ( dancing or tennis ) , or high intensity ( jogging or skiing ) and multiplying the reported frequency of the activity by 2.5 , 5 , and 7.5 , respectively . Weight ( in light indoor clothes with shoes removed ) was recorded with a balance beam scale , and height was measured using a st and ard held-expiration technique with a wall-mounted Harpenden stadiometer [ 17 ] . Maximal right knee extension , triceps ( arm extension ) , and hip abduction torque strength were measured with a h and -held isometric dynamometer ( Sparks Instruments and Academics , Coralville , Iowa ) . Grip strength of the right and left h and was assessed as the average of two attempts with the dynamometer . Waist , hip , and abdominal circumferences were measured using st and ard methods [ 18 ] . Statistical Methods The cohort was r and omly divided into equal-sized ( n = 4852 ) training and validation groups . In the training group , we analyzed potential associations with bone mass in univariate analyses , adjusted for age . We then adjusted associations ( P < 0.05 ) for other plausible confounding effects . For example , associations between the use of thiazide diuretics and bone mass were also adjusted for body weight , because those who were taking diuretics tended to be heavier . Potentially nonlinear associations between bone mass and continuous variables , such as calcium intake , were examined by plotting bone mass against the median of each decile of the predictor variable . Associations were tested for statistical significance with simple linear regression , Student t-test , or analysis of variance . Variables that were associated with bone mass in univariate analyses ( P < 0.05 ) were examined by multivariate analyses using PROC GLM ( SAS Institute , Inc. , Cary , North Carolina ) . Some categories of predictor variables , such as calcium intake and muscle strength , contained several variables associated with bone mass in univariate analyses . After examining these variables for multicollinearity , separate models for strength , family history of fractures , dietary calcium , and physical activity were analyzed to determine the individual variables that explained most of the variance of bone mass within each category . For example , grip strength explained most of the variance for bone mass related to strength ; thus , we selected this variable as the measure of strength for subsequent multivariate analyses . Both current dietary calcium and calcium from milk ( ingested between ages 18 to 50 years ) contributed to bone mass variance ; therefore , both were included in the final multivariate models . A history of any maternal fracture after age 50 accounted for most of the bone mass variance from family history , and intensity-weighted lifetime physical activity accounted for most of the variance from physical activity . Selected variables ( see Table 2 ) were then entered into a single multivariate model . We found that results from multivariate models were very similar in both training and validation groups ; thus results are reported for the entire ( combined ) cohort . Results were generally similar for the three bone mass sites , and for those analyses that were concordant at all three sites , only the results for the distal radius are presented . We presented results at the other two sites only when they differed from the distal radius . Results The average age at enrollment was 71.1 years , and the age distributions were similar in the training and validation groups ( Table 1 ) . Thirteen percent of patients reported a previous wrist or hip fracture . Table 1 . Baseline Characteristics of Patients Demographic and Anthropometric Data Bone mass was strongly and inversely associated with age , decreasing by approximately 5 % with every additional 5 years of age after 65 years ( Table 2 ) . Northern European ancestry , hair color , and educational level were not associated with bone mass ( Table 3 ) . Table 2 . Univariate and Multivariate Correlates of Distal Radius Bone Mass Table 3 . Variables Not Associated with Distal Radius Bone Mass , Age-Adjusted Univariate Analyses * Several anthropometric measurements were strongly associated with bone mass ( see Table 2 ) . Both weight [ in kilograms ] and obesity ( as Quetelet index , in kilograms per square meter ) were associated with increased bone mass : after adjusting for age , bone mass increased 5.0 % for every 10-kg increase in weight ( Figure 1 ) . Although weight and Quetelet were highly correlated ( r = 0.91 ) , weight was more strongly associated with bone mass Although osteoporosis is an age-related disorder , the accelerated bone loss observed in postmenopausal women may be preventable with early diagnosis and adequate estrogen replacement . In a prospect i ve study , we investigated the effect of oral estrogen replacement using conjugated estrogens ( Premarin , 0.625 mg ) or micronized 17 beta-estradiol ( Estrace , 1 mg ) versus no estrogen in sequential single-photon bone density measurements over 3-year intervals in 397 postmenopausal women . Estradiol , 1 mg , and conjugated estrogens , 0.625 mg , were equally effective in regarding bone loss . The rate of bone loss was about the same for estrogen users regardless of age ( 51 to 80 years ) and was approximately one third that of nonusers . Among nonusers a uniform accelerated rate of bone loss of 2.5 % per year was noted between 56 and 70 years old , whereas between the ages of 51 and 55 years and after age 70 years , the rate of bone loss was significantly less . Ever users over age 65 years showed continued protection from bone loss as long as estrogen therapy was continued . Previous estrogen users who stopped estrogen after age 65 years lost bone more rapidly than women of similar age who had never taken estrogen . Thus to prevent accelerated bone loss in postmenopausal women , we recommend early and continued hormone replacement for life . Estrogen nonusers should be monitored at regular intervals to minimize accelerated bone loss Quality of care can be measured by using either processes or outcomes . Each method has its strengths and limitations ( 1 ) . With the concurrence of the Assessing Care of Vulnerable Elders ( ACOVE ) Policy Advisory Committee [ 2 ] , we chose to assess the care of vulnerable elders by using processes rather than outcomes . We did so because 1 ) processes are a more efficient measure of quality ; 2 ) for most conditions there are insufficient information in the medical record and a paucity of vali date d models to adequately adjust outcomes for differences in case mix between providers ; and 3 ) ultimately , processes of care are amenable to direct action by providers . To be a valid measure of quality , a health care process must be strongly linked to an outcome that is important to patients . Ideally , high- quality published studies would link performance of all such processes to outcomes ; however , few health care processes are supported by high- quality evidence ( 3 ) . Even when a process is supported by strong evidence from r and omized clinical trials , the inclusion and exclusion criteria of the clinical trials leave the evidence directly applicable to only a narrow group of patients ( 4 , 5 ) . This is particularly true for vulnerable elders , who are typically excluded from clinical trials ( 6 ) . Therefore , as we developed the ACOVE quality indicators , we used expert opinion to interpret the available evidence for applicability to vulnerable elders . Our methods entailed a literature review and several levels of expert opinion ( Figure ) , which we explain in detail . Figure . Assessing Care of Vulnerable Elders ( ACOVE ) method for developing quality indicators for vulnerable elders . Methods Development of Draft Process Indicators For each ACOVE condition that we selected for quality improvement in vulnerable elders ( 2 ) , we identified a content expert , who worked as a team with another project member knowledgeable about systematic review s and quality indicator development . Together , the content expert and project member developed potential quality indicators from existing guidelines , review criteria , and expert opinion . Because practice guidelines and existing quality indicators are seldom referenced in the traditional scientific data bases , we used various search strategies to locate these material s. In addition to search ing MEDLINE , we search ed the following sources : CONQUEST 1.1 ( A Computerized Needs-Oriented Quality Measurement Evaluation System ) ( 7 ) ; DEMPAQ : A Project to Develop and Evaluate Methods to Promote Ambulatory Care Quality ( 8) ; Directory of Clinical Practice Guidelines ( 9 ) ; Guide to Clinical Preventive Services ( 10 ) ; HEDIS 3.0 : Health Plan Employer Data and Information Set ( 11 ) ; National Guideline Clearinghouse ( 12 ) ; National Library of Health Care Indicators ( 13 ) ; and The Medical Outcomes & Guidelines Source book ( 14 ) . We also h and search ed the tables of contents of all issues of The Journal of the American Medical Association and Medical Care published April through November 1998 for relevant practice guidelines and quality indicators . Furthermore , we requested practice guidelines and quality indicators from the following agencies and organizations : Administration on Aging ( AOA ) ; Agency for Health Care Policy and Research (AHCPR)now known as Agency for Healthcare Research and Quality ( AHRQ ) ; Centers for Disease Control and Prevention ( CDC ) ; Department of Health and Human Services ( DHHS ) ; Department of Veterans Affairs ; Foundation for Accountability ( FACCT ) ; Health Care Financing Administration ( HCFA ) ; HCFA/Connecticut Peer Review Organization ; Joint Commission on Accreditation of Healthcare Organizations ( JCAHO ) ; National Committee for Quality Assurance ( NCQA ) ; and National Institutes of Health ( NIH ) . By using the quality indicators identified through this process , as well as using expert opinion and existing guidelines , the content expert developed 20 to 30 preliminary quality indicators for further review . Potential indicators were constructed in an IFTHENBECAUSE format : IF refers to the clinical characteristics that describe persons eligible for the quality indicator ; THEN indicates the actual process that should or should not be performed ; and BECAUSE refers to the expected health impact if the indicator is performed . For example , IF a vulnerable elder has heart failure with an ejection fraction of 40 % or less , THEN an angiotensin-converting enzyme ( ACE ) inhibitor should be offered BECAUSE treatment with ACE inhibitors improves longevity . We circulated this initial set of potential quality indicators to other clinical experts for their review . On the basis of review ers ' comments , we narrowed down the initial set to the 10 to 25 most promising indicators for future development . Review of Scientific Literature Next , we assessed the published evidence supporting a link between the process specified in each quality indicator and patient outcomes . To do so , we performed a systematic review on each quality indicator by using the essence of the Cochrane Collaboration 's methods (15)except that we used a single review er to screen and assess studies . With the assistance of a reference librarian , we electronically search ed MEDLINE , EMBASE , The Cochrane Data base of Systematic Review s , HealthSTAR , Ageline , and other specialized data bases on a condition-specific basis by using keywords and free-text terms to identify potentially relevant studies . For most conditions , the search es were not restricted by language . The content expert review ed the retrieved citations by using a three-step process : First , the titles were review ed for possibly relevant studies ; the abstract s associated with the titles that passed the first round of screening were then review ed ; and , finally , the full articles of abstract s that passed the second round of screening were review ed . Abstract s and articles were not masked for review . To be accepted , titles and abstract s had to contain information indicating that the full article probably reported evidence on the potential relationship between the process in question and better outcomes in humans . We excluded animal studies , letters , review articles , and other articles that did not report original data . In review ing full articles , we gave priority to evidence from studies with the strongest design s that were relevant to the potential quality indicator being examined . In general , this meant that we chose r and omized clinical trials for questions about the efficacy or effectiveness of interventions and prospect i ve cohort studies to answer questions about risk or prognosis . We considered such evidence to be direct evidence , and we judged direct evidence in elderly persons to be the strongest level of evidence available . In the absence of direct evidence in elderly persons , we performed search es for direct evidence in other groups . Indirect evidence that from less rigorous design sin elderly or nonelderly persons was review ed if the available direct evidence was insufficient . When both direct evidence and indirect evidence were lacking , we included the statements of authoritative bodies ( for example , specialty societies , National Institutes of Health consensus development conferences , or Agency for Health Care Policy and Research practice guidelines ) . After review ing all of the relevant articles , the content expert prepared a monograph detailing each of the quality indicators and summaries of the evidence supporting them . This monograph was sent to one or more peer review ers , who were asked to assess the quality of the monograph according to the following guidelines : 1 ) Is the review complete in terms of both the proposed quality criteria and the evidence ? 2 ) Is the review fair ( that is , is the presentation of the evidence unbiased ) ? The authors subsequently revised the monographs on the basis of review ers ' comments in a manner analogous to the response to a critique of a journal article : Each comment was addressed in turn , and the author provided an appropriate revision or stated the reason why he or she believed that no revision was indicated . Expert Panels We convened two multidisciplinary groups , each composed of 12 clinical experts , to interpret the supporting evidence detailed in the monographs and to select quality indicators for further consideration . Each panel of experts considered a separate set of ACOVE conditions . Table 1 lists the members of the panels and the conditions they considered . Table 1 . ACOVE Expert Panels To assess the expert opinions of the panelists , we used a modified version of the R AND /UCLA Appropriateness Method ( 16 , 17 ) . In brief , the method entails two rounds of anonymous ratings on a riskbenefit scale ranging from 1 to 9 and a face-to-face group discussion between rounds . Each panelist has equal weight in determining the final ratings . The reproducibility of the R AND /UCLA Appropriateness Method is consistent with that of well-accepted diagnostic tests , such as the interpretation of coronary angiography and screening mammography ( 18 ) . It also has content , construct , and predictive validity ( 5 , 17 , 19 , 20 ) . In this application of the method , we sent each panelist the proposed quality indicators and the relevant condition-specific monographs . We asked the panelists to assess the validity of each proposed indicator on a scale of 1 to 9 , in which 1 was definitely not valid and 9 was definitely valid . We considered an indicator to be valid if 1 ) adequate scientific evidence or professional consensus supported a link between the process specified by the indicator and a health benefit to the patient ; 2 ) a physician or health plan with high rates of adherence to the indicator would be considered a higher- quality provider ; and 3 ) the physician or health plan influenced a majority of factors that determine adherence to the indicator ( such as smoking cessation ) . Each panelist was instructed to rate each potential quality indicator for validity and return the ratings to us before the face-to-face This open , prospect i ve therapeutic trial studied the effects of regular moderate and rogen supplementation on bone mineral density in eugonadal men with established osteoporosis , and collected data on the safety of and rogen therapy used in this setting . 23 men , aged 34 - 73 years , with vertebral crush fractures and back pain , in whom secondary causes of osteoporosis had been excluded , were treated with fortnightly intramuscular injections of 250 mg testosterone esters ( Sustanon 250(R ) ) for 6 months . Blood pressure was recorded monthly ; fasting lipids , glucose , haematocrit , plasma viscosity , and testosterone levels were measured every 3 months . Psychological effects were assessed using the Hospital Anxiety and Depression Scale ( HADS ) and General Health Question naire ( GHQ ) , together with question ing on libido changes . Principal outcomes measured were changes in bone mineral density at the hip and spine by dual-energy X-ray absorptiometry ( DEXA ) over the treatment period . 21 men completed the study period . Mean bone mineral density at the lumbar spine increased from 0.799 g/cm(2 ) to 0.839 g/cm(2 ) during treatment ( p < 0 . 001 ) , a rise of 5 % in 6 months . Bone mineral density at the hip did not change . There were significant , favorable changes in diastolic blood pressure ( -4.7 mmHg , p < 0.01 ) , serum triglyceride levels ( -0.405 mmol/L , p < 0.01 ) , and total cholesterol ( -0.27 mmol/L , p < 0.05 ) . Adverse changes included a fall in HDL cholesterol ( -0.087 mmol/L , p < 0.05 ) and a rise in plasma viscosity which was significant at 3 months but not at 6 months . The expected rises in hematocrit ( 0.434 to 0.456 ) and FAI ( 0.504 to 0.887 ) occurred . We conclude that testosterone supplementation significantly increased bone mineral density in this heterogeneous group of men with idiopathic primary osteoporosis , without an overall adverse effect on cardiovascular risk factors . This treatment warrants further evaluation in a r and omized , controlled trial Malabsorption of calcium is a common finding in patients with postmenopausal osteoporosis ( 1 , 2 ) . In a number of studies serum 1,25 dihydroxyvitamin D levels were found to be significantly lower in osteoporotic patients , which could account for the calcium absorptive defect ( 3–6 ) . Based on these findings , we studied the effects of synthetic calcitriol ( Rocaltrol ) in women with osteoporosis . We showed that calcitriol , 0.25 μg twice daily , improved and normalized the absorption of calcium in all patients and improved calcium balance ( 7 ) . Urine hydroxyproline , which is a measure of bone resorption , decreased significantly after 2 years of treatment with Rocaltrol . Because of these preliminary findings , further clinical studies were carried out at two centers using a variable dose of Rocaltrol . In these studies we focused on the effectiveness of Rocaltrol in preventing vertebral fractures in patients with spinal osteoporosis . Methods The results from two centers have been analyzed both as separate groups and as one combined group . One study was performed at the Mayo Clinic ( Protocol 861 ) and the other at Creighton University ( Protocol 860 ) . In both centers the studies performed were double blind and r and omized , and compared the effect of placebo against Rocaltrol for a period of 1 year . At the end of 1 year all patients on placebo were crossed over to treatment with Rocaltrol and followed for 2 more years . Patients initially treated with Rocaltrol were followed for an additional 2 years , thus yielding treatment data extending to 3 years in a number of patients . In the study design , patients were given Rocaltrol at a starting dose of 0.25 μg twice daily , if hypercalcemia and hypercalciuria did not occur the dose then was increased to 0.75 μg or 1.0 μg daily at the discretion of the investigator Background . The effectiveness of calcium in retarding bone loss in older postmenopausal women is unclear . Earlier work suggested that the women who were most likely to benefit from calcium supplementation were those with low calcium intakes . Methods . We undertook a double-blind , placebo-controlled , r and omized trial to determine the effect of calcium on bone loss from the spine , femoral neck , and radius in 301 healthy postmenopausal women , half of whom had a calcium intake lower than 400 mg per day and half an intake of 400 to 650 mg per day . The women received placebo or either calcium carbonate or calcium citrate malate ( 500 mg of calcium per day ) for two years . Results . In women who had undergone menopause five or fewer years earlier , bone loss from the spine was rapid and was not affected by supplementation with calcium . Among the women who had been postmenopausal for six years or more and who were given placebo , bone loss was less rapid in the group with the higher dietary calcium intake . In those with the lower calcium intake , calcium citrate malate prevented bone loss during the two years of the study ; its effect was significantly different from that of placebo ( P less than 0.05 ) at the femoral neck ( mean change in bone density [ + /- SE ] , 0.87 + /- 1.01 percent vs. -2.11 + /- 0.93 percent ) , radius ( 1.05 + /- 0.75 percent vs. -2.33 + /- 0.72 percent ) , and spine ( -0.38 + /- 0.82 percent vs. -2.85 + /- 0.77 percent ) . Calcium carbonate maintained bone density at the femoral neck ( mean change in bone density , 0.08 + /- 0.98 percent ) and radius ( 0.24 + /- 0.70 percent ) but not the spine ( -2.54 + /- 0.85 percent ) . Among the women who had been postmenopausal for six years or more and who had the higher calcium intake , those in all three treatment groups maintained bone density at the hip and radius and lost bone from the spine . Conclusions . Healthy older postmenopausal women with a daily calcium intake of less than 400 mg can significantly reduce bone loss by increasing their calcium intake to 800 mg per day . At the dose we tested , supplementation with calcium citrate malate was more effective than supplementation with calcium carbonate Bone mass was measured prospect ively in 73 women during the period immediately after menopause . By comparing the rates of loss at three skeletal sites , we assessed the protective effects of calcium supplements given alone or combined with low-dosage estrogen therapy . After 2 years of follow-up , spinal trabecular mineral content , measured by quantitative computed tomography , decreased by a mean of 9.0 % ( p = 0.002 compared with baseline ) in untreated women and a mean of 10.5 % ( p = 0.0001 ) in women given calcium supplements alone . By contrast , women given conjugated estrogens , 0.3 mg/d , with calcium supplements showed an insignificant increase of 2.3 % . Significant losses of a lesser magnitude were seen in the appendicular cortical skeleton of women not receiving therapy and in those receiving calcium alone , but no significant changes were observed in women receiving estrogen with calcium The effect on forearm bone mineral content ( BMC ) of initiation and withdrawal of oestrogen/gestagen treatment was studied in a r and omised trial in 94 healthy female volunteers six months to three years after the menopause . BMC was measured every three months for three years . BMC increased by 3.7 % ( p less than 0.001 ) during three years ' hormone treatment and decreased by 5.7 % ( p less than 0.001 ) during three years ' placebo treatment . The annual rate of bone loss after discontinuation of hormone therapy was identical with the bone loss in the placebo group . The present study indicates that even temporary hormone replacement therapy after the menopause will have a lasting beneficial effect on bone mass OBJECTIVE To evaluate the tolerance and effectiveness of transdermal estrogen for women with established postmenopausal osteoporosis and vertebral fractures . DESIGN Double-blind , r and omized , placebo-controlled clinical trial lasting 1 year . SETTING Referral-based outpatient clinic . PATIENTS Seventy-five postmenopausal women , 47 to 75 years of age , with one or more vertebral fractures due to osteoporosis . INTERVENTIONS Thirty-nine women received dermal patches delivering 0.1 mg of 17 beta-estradiol for days 1 to 21 and oral medroxyprogesterone acetate for days 11 to 21 of a 28-day cycle . Another 39 women received placebo . MEASUREMENTS Bone turnover assessed by biochemical markers and iliac bone histomorphometry ; bone loss assessed by serial measurement of bone density ; and vertebral fracture rate . RESULTS Compared with the placebo group , the median annual percentage change in bone mineral density in the estrogen group reflected increased or steady-state bone mineral density at the lumbar spine ( 5.3 compared with 0.2 ; P = 0.007 ) , femoral trochanter ( 7.6 compared with 2.1 ; P = 0.03 ) , and midradius ( 1.0 compared with -2.6 , P less than 0.001 ) but showed no significant difference at the femoral neck ( 2.6 compared with 1.4 ; P = 0.17 ) . Estrogen treatment uniformly decreased bone turnover as assessed by several methods including serum osteocalcin concentration ( median change , -0.35 compared with 0.02 nmol/L ; P less than 0.001 ) . Histomorphometric evaluation of iliac biopsy sample s confirmed the effect of estrogen on bone formation rate per bone volume ( median change , -12.9 compared with -6.2 % per year ; P = 0.004 ) . Also , 8 new fractures occurred in 7 women in the estrogen group , whereas 20 occurred in 12 women in the placebo group , yielding a lower vertebral fracture rate in the estrogen group ( relative risk , 0.39 ; 95 % CI , 0.16 to 0.95 ) . CONCLUSIONS Transdermal estradiol treatment is effective in postmenopausal women with established osteoporosis The purpose of this study was to investigate the effects of 10 years of hormone replacement therapy ( HRT ) in postmenopausal women on bone mineral density of the lumbar spine ( L-BMD ) and bone mineral content of the distal forearm ( F- BMC ) . A total of 151 women were enrolled in the study , 100 of whom were r and omized to receive oral HRT ( equally divided between a continuous combined and a sequential treatment regimen ) , with the remaining 51 receiving placebo or no treatment . The study was double-blind for the first 24 months , followed by 8 years of open-label follow-up . Total treatment duration was 10 years . At the end of 10 years , 38 % of women r and omized to continuous combined HRT remained on therapy compared with 22 % of those who had received sequential HRT and 49 % of the untreated group . A further 18 % of women originally r and omized to HRT had switched to other regimens . After 10 years of therapy , L-BMD was found to be significantly higher in HRT-treated women than in those who remained untreated ( 14.5 % ; p < 0.001 ) , corresponding to an increase in L-BMD of 13.1 % from baseline values on HRT compared with a reduction in L-BMD of 4.7 % without therapy . L-BMD increased by 15.9 % in women receiving continuous combined therapy compared with 11.1 % in those on sequential HRT ; however , intergroup differences were not statistically significant . F- BMC decreased by 0.7 % over the 10 year period in the HRT treatment groups compared with a reduction of 17.6 % in untreated women ( p < 0.001 ) . Mean F- BMC was 20.3 % higher in women who had received HRT than in those who had not received therapy at the end of the 10 year follow-up . In conclusion , 10 years of treatment with HRT result ed in a substantial increase in L-BMD , with F- BMC also significantly higher in the HRT group than in untreated women . These results confirm that long-term HRT exerts a continuous effect against bone loss in postmenopausal women BACKGROUND Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons . METHODS We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density , biochemical measures of bone metabolism , and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home . They received either 500 mg of calcium plus 700 IU of vitamin D3 ( cholecalciferol ) per day or placebo . Bone mineral density was measured by dual-energy x-ray absorptiometry , blood and urine were analyzed every six months , and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records . RESULTS The mean ( + /-SD ) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows : femoral neck , + 0.50+/-4.80 and -0.70+/-5.03 percent , respectively ( P=0.02 ) ; spine,+2.12+/-4.06 and + 1.22+/-4.25 percent ( P=0.04 ) ; and total body , + 0.06+/-1.83 and -1.09+/-1.71 percent ( P<0.001 ) . The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year , but it was significant only for total-body bone mineral density in the second and third years . Of 37 subjects who had nonvertebral fractures , 26 were in the placebo group and 11 were in the calcium-vitamin D group ( P=0.02 ) . CONCLUSIONS In men and women 65 years of age or older who are living in the community , dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck , spine , and total body over the three-year study period and reduced the incidence of nonvertebral fractures Treatment of 63 oophorectomised women with oestrogen for five years prevented the reduction in bone mineral content observed in 57 women treated with a placebo preparation . When onset of therapy was delayed for three to six years there was a highly significant increase in bone mineral content mainly during the first three years of treatment . During the next two years there was no further increase in bone mineral , while the placebo-treated groups continued to lose bone at about 1 % per annum . In association with the changes in bone mass , the expected biochemical effects of oestrogen therapy also persisted for at least three years , and were compatible with a prolonged increase in parathyroid activity but a reduction in bone turnover In a controlled single blind study to determine the minimal effective dose of estrogen for protection against bone loss , conjugated equine estrogens in doses of 0.625 and 1.25 mg per day were equally effective in reducing bone loss in postmenopausal and oophorectomized women when bone mass was estimated by single-photon absorptiometry or radiogrammetry . Daily dose levels of less than 0.625 mg were essentially ineffective . Fifty percent response level was calculated to be 0.45 mg per day . Concomitant biochemical effects , reduction in urine calcium and hydroxyproline , were compatible with the observed effects on bone mineral To evaluate the efficacy of therapeutic exercises in the prevention of bone loss , 146 untrained healthy postmenopausal women were prospect ively controlled for ( mean + /- SD ) 3.0 + /- 1.3 yr . Eighty-two subjects aged ( mean + /- SD ) 61.5 + /- 6.1 yr participated in an exercise program ( group 1 ) and sixty-four aged ( mean + /- SD ) 59.1 + /- 7.4 yr served as controls ( group 2 ) . Periodically during the study period , we measured women 's bone density at two forearm sites and recorded their physical activities . Because bone loss differed insignificantly between the groups , group 1 was retrospectively subdivided into group 1a ( regular exercise ) and group 1b ( nonregular exercise ) . The results showed that only 39 women ( 48 percent ) of group 1 ( group 1a ) performed the exercise program regularly for the prescribed time . Regression slopes of forearm bone density ( distal and proximal scans ) v time were significantly less negative ( P < 0.05 ) in group 1a ( distal , -0.3 percent and proximal , -0.7 percent per year ) than in group 1b ( distal , -1.8 percent and proximal -1.6 percent per year ) or group 2 ( distal , -1.7 percent and proximal , -1.9 percent per year ) . We conclude that in untrained elderly women , poor compliance with regular physical activities is a main factor , explaining the lack of response to exercise treatment in prevention of osteoporosis 100 women who had taken part in a prospect i ve controlled trial of oestrogen therapy for prevention of post-oophorectomy bone loss were review ed after a median follow-up period of nine years . A significant reduction in height occurred among the placebo-treated group , but not in the group treated with mestranol ( mean 23 x 3 micrograms/day ) . The placebo-treated group had a higher spine score , lower central vertebral height , and larger wedge-angle than the oestrogen group . Within each group none of these spinal morphometric changes correlated with changes in mineral content of metacarpal or radial bones as measured by photon absorptiometry or X-ray densitometry , although both peripheral and central measurements showed highly significant differences between groups . Oestrogen treatment , therefore , prevents against central , as well as peripheral , bone loss , and reduces the incidence of vertebral compression BACKGROUND The efficacy of antiresorptive therapy in preventing fractures in women at highest fracture risk , such as very elderly women or those with severe osteoporosis , is uncertain . PARTICIPANTS AND METHODS Using data from a double-blind , r and omized , placebo-controlled clinical trial that enrolled 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone mineral density ( BMD ) and existing vertebral fractures , we examined the consistency of the effect of treatment with alendronate sodium in preventing fractures within a priori-specified risk subgroups defined at baseline by age , bone density , number of preexisting vertebral fractures , and history of postmenopausal fracture . The women were r and omized to oral administration of alendronate or placebo and followed up for an average of 2.9 years . The initial dose of alendronate sodium was 5 mg/d ; the dosage was increased from 5 to 10 mg/d at 24 months . New vertebral fractures , the primary end point of this arm of the trial , were defined by morphometry as a decrease of 20 % and at least 4 mm in any vertebral height between baseline and a follow-up radiograph at 36 months . Incident clinical fractures , the secondary end point , included nonspine and clinical ( symptomatic ) vertebral fractures . All clinical fractures were confirmed with x-ray film reports or , in the case of clinical vertebral fractures , x-ray films . RESULTS Overall , there was a 47 % significant reduction in risk of new vertebral fractures in the alendronate group compared with the placebo group . The reduction in risk of new vertebral fracture was consistent across fracture risk categories including age ( relative risk [ RR ] , 0.49 in women < 75 years compared with 0.62 in those > or = 75 years ) , BMD ( RR , 0.54 in women with a femoral neck BMD < 0.59 g/cm2 [ median ] compared with 0.53 in those with a BMD > or = 0.59 g/cm2 ) , and number of preexisting vertebral fractures ( RR , 0.58 in women with 1 vertebral fracture compared with 0.52 in those with > or = 2 ) . The overall significant 28 % reduction in risk of incident clinical fractures in the alendronate group compared with the placebo group was also observed within these subgroups . Compared with the number of lower-risk women , a similar or smaller number of high-risk women needed to be treated to prevent 1 fracture . For example , 8 women aged 75 years or older compared with 9 women younger than 75 years , or 4 women with 2 or more existing vertebral fractures compared with 16 women with 1 existing vertebral fracture , needed to be treated with alendronate for 5 years to prevent 1 new vertebral fracture . CONCLUSIONS Alendronate effectively reduces fracture risk in postmenopausal women with vertebral fractures and low BMD , including those women at highest risk because of advanced age or severe osteoporosis . Since the risk reductions observed with alendronate treatment were consistent within fracture risk categories , more fractures were prevented by treating women at highest risk |
2,213 | 24,835,434 | Aerobic exercise decreased the adhesion molecules , vascular cell adhesion molecule-1 ( VCAM-1 ) and intercellular adhesion molecule-1 ( ICAM-1 ) ( moderate and high evidence , respectively ) , while effects of PA on E- and P-selectin were inconclusive .
PA decreases C-reactive protein ( CRP ) ( high evidence ) .
The angiogenic actors , endothelial progenitor cells ( EPCs ) are increased ( high evidence ) and VEGF is decreased ( moderate evidence ) by PA .
The effect of PA on these factors seems to depend on the type and duration of exercise intervention and patient factors , such as presence of ischemia .
As presented in this review , there is a high level of evidence that physical activity positively affects key players in atherosclerosis development .
These effects could partly explain the scientifically proven anti-atherogenic effects of PA , and do have important clinical implication | OBJECTIVE This systematic review aim ed to summarize published papers on the effect of physical activity (PA)/exercise on key atherosclerotic factors in patients with risk factors for or established cardiovascular disease ( CVD ) . | BACKGROUND Interleukin-6 ( IL-6 ) plays a central role in inflammation and tissue injury . However , epidemiological data evaluating the role of IL-6 in atherogenesis are sparse . METHODS AND RESULTS In a prospect i ve study involving 14 916 apparently healthy men , we measured baseline plasma concentration of IL-6 in 202 participants who subsequently developed myocardial infa rct ion ( MI ) and in 202 study participants matched for age and smoking status who did not report vascular disease during a 6-year follow-up . Median concentrations of IL-6 at baseline were higher among men who subsequently had an MI than among those who did not ( 1.81 versus 1 . 46 pg/mL ; P=0.002 ) . The risk of future MI increased with increasing quartiles of baseline IL-6 concentration ( P for trend < 0.001 ) such that men in the highest quartile at entry had a relative risk 2.3 times higher than those in the lowest quartile ( 95 % CI 1.3 to 4.3 , P=0.005 ) ; for each quartile increase in IL-6 , there was a 38 % increase in risk (P=0.001).This relationship remained significant after adjustment for other cardiovascular risk factors , was stable over long periods of follow-up , and was present in all low-risk subgroups , including nonsmokers . Although the strongest correlate of IL-6 in these data was C-reactive protein ( r=0.43 , P<0.001 ) , the relationship of IL-6 with subsequent risk remained after control for this factor ( P<0.001 ) . CONCLUSIONS In apparently healthy men , elevated levels of IL-6 are associated with increased risk of future MI . These data thus support a role for cytokine-mediated inflammation in the early stages of atherogenesis Background Significant regression of coronary and femoral atherosclerotic lesions has been documented by angiographic studies using aggressive lipid-lowering treatment . This study tested the applicability and effects of intensive physical exercise and low-fat diet on coronary morphology and myocardial perfusion in nonselected patients with stable angina pectoris . Methods and Results Patients were recruited after routine coronary angiography for stable angina pectoris ; they were r and omized to an intervention group ( n = 56 ) and a control group on “ usual care ” ( n = 57 ) . Treatment comprised intensive physical exercise in group training sessions ( minimum , 2 hr/wk ) , daily home exercise periods ( 20 min/d ) , and low-fat , low-cholesterol diet ( American Heart Association recommendation , phase 3 ) . No lipid-lowering agents were prescribed . After 12 months of participation , repeat coronary angiography was performed ; relative and minimal diameter reductions of coronary lesions were measured by digital image processing . Change in myocardial perfusion was assessed by 201TI scintigraphy . In patients participating in the intervention group , body weight decreased by 5 % ( p<0.001 ) , total cholesterol by 10 % ( p<0.001 ) , and triglycerides by 24 % ( p<0.001 ) ; high density lipoproteins increased by 3 % ( p = NS ) . Physical work capacity improved by 23 % ( p<0.0001 ) , and myocardial oxygen consumption , as estimated from maximal rate-pressure product , by 10 % , ( p<0.05 ) . Stress-induced myocardial ischemia decreased concurrently , indicating improvement of myocardial perfusion . Based on minimal lesion diameter , progression of coronary lesions was noted in nine patients ( 23 % ) , no change in 18 patients ( 45 % ) , and regression in 13 patients ( 32 % ) . In the control group , metabolic and hemodynamic variables remained essentially unchanged , whereas progression of coronary lesions was noted in 25 patients ( 48 % ) , no change in 18 patients ( 35 % ) , and regression in nine patients ( 17 % ) . These changes were significantly different from the intervention group ( p<0.05 ) . Conclusions In patients participating in regular physical exercise and low-fat diet , coronary artery disease progresses at a slower pace compared with a control group on usual care Alterations in circulating angiogenic cells ( CAC ) and endothelial progenitor cells ( EPC ) , known to contribute to endothelial repair , could explain the reversal of endothelial function in response to exercise training . Moreover , training-induced vascular remodeling might affect the acute response of EPC and CAC following a single exercise bout . We studied the impact of exercise training on CAC function and numbers of CD34+/KDR+ EPC in patients with chronic heart failure ( CHF ) and we assessed the effect of acute exercise on CAC and EPC in sedentary and trained patients . Twenty-one sedentary CHF patients underwent 6-month exercise training and were compared to a non-trained control group ( n = 17 ) and 10 healthy age-matched subjects . At baseline and follow-up , flow-mediated dilation was assessed and grade d exercise testing ( GXT ) was performed . Before and immediately after GXT , CAC migratory capacity was assessed in vitro and circulating CD34+/KDR+ EPC were quantified using flow cytometry . At baseline , CAC migration was significantly impaired in sedentary CHF patients but normalized acutely after GXT . Training corrected endothelial dysfunction , which coincided with a 77 % increase in CAC migration ( P = 0.0001 ) . Moreover , the GXT-induced improvement detected at baseline was no longer observed after training . Numbers of CD34+/KDR+ EPC increased following 6-month exercise training ( P = 0.021 ) , but were not affected by GXT , either prior or post-training . In conclusion , the present findings demonstrate for the first time that exercise training in CHF reverses CAC dysfunction and increases numbers of CD34+/KDR+ EPC , which is accompanied by improvement of peripheral endothelial function . The acute exercise-induced changes in CAC function wane with exercise training , suggesting that repetitive exercise bouts progressively lead to functional endothelial repair Background Coronary heart disease as well as major cardiovascular risk factors are associated with elevated levels of proinflammatory markers . There is , however , limited information about how changes in lifestyle improving the cardiovascular risk profile influence these levels . The aim of the study was to evaluate whether changes in lifestyle measures with special attention to physical activity , were associated with the levels of such markers . Design Coronary heart disease patients ( n = 197 ) were r and omized to either a comprehensive lifestyle intervention programme comprising regular physical activity , low fat diet and smoking cessation , or usual care with routine follow-up in the outpatient clinic for 6 months . An exercise test and fasting blood sample s analysed for soluble cell adhesion molecules , C reactive protein and pro-inflammatory cytokines were evaluated before and at the end of the study . Results Improved diet , physical performance and reduction in smoking were obtained in the intervention programme when compared with usual care patients , but no significant group differences in levels of inflammatory markers were observed . In the total population , however , physical performance significantly and inversely predicted levels of soluble cell adhesion molecule 1 , ( P>0.001 ) , C-reactive protein ( P>0.001 ) and interleukin-6 ( P=0.01 ) at 6 months . Smokers had elevated levels of soluble cell adhesion molecule 1 when compared with non-smokers ( P=0.011 ) . Conclusions We demonstrated that physical performance is inversely correlated with levels of pro-inflammatory markers in coronary heart disease patients , possibly retarding the process of atherosclerosis . No effect on inflammatory markers was obtained with a 6-month lifestyle intervention programme when compared with patients who received usual care follow-up . Eur J Cardiovasc Prev Rehabil 13:356 - 362 © 2006 The European Society of Background —C-reactive protein ( CRP ) and interleukin (IL)-6 are important risk factors for atherosclerosis and coronary heart disease . In the present study , we examined serum levels of CRP and IL-6 , IL-6 production by monocytes , and the effect of nasal continuous positive airway pressure ( nCPAP ) in patients with obstructive sleep apnea syndrome ( OSAS ) . Methods and Results —After polysomnography , venous blood was collected at 5 am from 30 patients with OSAS and 14 obese control subjects . Serum levels of CRP and IL-6 and spontaneous production of IL-6 by monocytes were investigated . In addition , the effects of 1 month of nCPAP were studied in patients with moderate to severe OSAS . Levels of CRP and IL-6 were significantly higher in patients with OSAS than in obese control subjects ( CRP P < 0.001 , IL-6 P < 0.05 ) . IL-6 production by monocytes was also higher in patients with OSAS than in obese control subjects ( P < 0.01 ) . In patients with OSAS , the primary factors influencing levels of CRP were severity of OSAS and body mass index and those influencing levels of IL-6 were body mass index and nocturnal hypoxia . nCPAP significantly decreased levels of both CRP ( P < 0.0001 ) and IL-6 ( P < 0.001 ) and spontaneous IL-6 production by monocytes ( P < 0.01 ) . Conclusions —Levels of CRP and IL-6 and spontaneous production of IL-6 by monocytes are elevated in patients with OSAS but are decreased by nCPAP . Therefore , OSAS is associated with increased risks for cardiovascular morbidity and mortality , and nCPAP may be useful for decreasing these risks Background Obesity is characterized by chronic mild inflammation and may influence the risk and progression of cancer . Purpose The current study is an exploratory analysis of the effect of a weight loss intervention that emphasized increased physical activity on inflammatory cytokines ( tumor necrosis factor-α [ TNF-α ] , interleukin-6 [ IL-6 ] , interleukin-8 [ IL-8 ] , and vascular endothelial growth factor [ VEGF ] ) at the end of the 16-week intervention period in overweight breast cancer survivors . Methods Study participants averaged 56 years of age ( N = 68 ) . Intervention participants ( n = 44 vs. 24 controls ) participated in a cognitive behavioral therapy-based weight management program as part of an exploratory r and omized trial . The intervention incorporated strategies to promote increased physical activity and diet modification . Baseline and 16-week data included height , weight , body composition , physical activity level , and biomarkers IL-6 , IL-8 , TNF-α , and VEGF . Results Weight loss was significantly greater in the intervention group than controls ( −5.7 [ 3.5 ] vs. 0.2 [ 4.1 ] kg , P < 0.001 ) . Paired t tests noted favorable changes in physical activity level ( P < 0.001 intervention , P = 0.70 control ) , marginally lower IL-6 levels ( P = 0.06 intervention , P = 0.25 control ) at 16 weeks for participants in the intervention group , and lower TNF-α levels for participants in the intervention ( P < 0.05 ) and control groups ( P < 0.001 ) . Increased physical activity was associated with favorable changes in IL-6 for participants in the intervention group ( R2 = 0.18 ; P < 0.03 ) . Conclusion Favorable changes in cytokine levels were observed in association with weight loss in this exploratory study with overweight breast cancer survivors BACKGROUND The purpose of this study was to determine the effects of systemic exercise training on endothelium-mediated arteriolar vasodilation of the lower limb and its relation to exercise capacity in chronic heart failure ( CHF ) . Endothelial dysfunction is a key feature of CHF , contributing to increased peripheral vasoconstriction and impaired exercise capacity . Local h and grip exercise has previously been shown to enhance endothelium-dependent vasodilation in conduit and resistance vessels in CHF . METHODS AND RESULTS Twenty patients were prospect ively r and omized to a training group ( n=10 , left ventricular ejection fraction [ LVEF ] 24+/-4 % ) or a control group ( n=10 , LVEF 23+/-3 % ) . At baseline and after 6 months , peak flow velocity was measured in the left femoral artery using a Doppler wire ; vessel diameter was determined by quantitative angiography . Peripheral blood flow was calculated from average peak velocity ( APV ) and arterial cross-sectional area . After exercise training , nitroglycerin-induced endothelium-independent vasodilation remained unaltered ( 271 % versus 281 % , P = NS ) . Peripheral blood flow improved significantly in response to 90 microg/min acetylcholine by 203 % ( from 152+/-79 to 461+/-104 mL/min , P<0.05 versus control group ) and the inhibiting effect of L-NMMA increased by 174 % ( from -46+/-25 to -126+/-19 mL/min , P<0.05 versus control group ) . Peak oxygen uptake increased by 26 % ( P<0.01 versus control group ) . The increase in peak oxygen uptake was correlated with the endothelium-dependent change in peripheral blood flow ( r=0.64 , P<0 . 005 ) . CONCLUSIONS Regular physical exercise improves both basal endothelial nitric oxide ( NO ) formation and agonist-mediated endothelium-dependent vasodilation of the skeletal muscle vasculature in patients with CHF . The correction of endothelium dysfunction is associated with a significant increase in exercise capacity OBJECTIVES To investigate the effects of exercise training on levels of circulating biomarkers associated with the progression of atherosclerosis and risk of cardiovascular events in patients with intermittent claudication . METHODS Circulating levels of soluble adhesion molecules ( sVCAM-1 , sICAM-1 , sE-selectin ) , high sensitivity C-reactive protein ( hs-CRP ) and stress proteins ( Hsp60 and Hsp70 ) in patients r and omised to a 24-week programme of arm- or leg-cranking exercise were compared with those in usual care controls . RESULTS Arm and leg exercise similarly improved lower-limb aerobic exercise capacity ( 20 % vs 19 % , respectively ; P<0.001 ) and maximum walking distance ( 30 % vs 35 % , respectively ; P<0.001 ) . Improvements in training limb-specific peak oxygen consumption were attenuated for patients in the highest vs lowest quartile for circulating sVCAM-1 levels at baseline ( 3 % vs 25 % respectively , P<0.001 ) . Although circulating hs-CRP levels tended to be lower in the arm-cranking group ( -1.55 [ 95 % CI : -1.06 to -2.26]mgl(-1 ) ) , exercise training had no effect on circulating levels of soluble adhesion molecules or stress proteins . CONCLUSIONS These findings suggest that high levels of circulating sVCAM-1 are associated with an attenuated exercise training response and that arm-cranking exercise may provide an effective stimulus for evoking systemic anti-inflammatory adaptations in patients with intermittent claudication Background —Monocyte chemoattractant protein-1 ( MCP-1 ) is a chemokine responsible for the recruitment of monocytes to sites of inflammation . MCP-1 appears to play a critical role at multiple stages in atherosclerosis , including the initiation of the fatty streak , promotion of plaque instability , and remodeling after myocardial infa rct ion . Methods and Results —MCP-1 was measured from frozen plasma specimens in 279 healthy volunteers and 2270 patients with acute coronary syndromes enrolled in the Oral Glycoprotein IIb/IIIa Inhibition with Orbofiban in Patients with Unstable Coronary Syndromes ( OPUS-TIMI ) 16 trial . Median [ 25th , 75th percentiles ] MCP-1 levels were 157 [ 124 , 196 ] pg/mL in healthy volunteers and 178 [ 128 , 238 ] pg/mL in the OPUS-TIMI 16 population ( P < 0.001 ) . In OPUS-TIMI 16 , baseline MCP-1 levels were associated with older age , female sex , hypertension , diabetes , prior coronary disease , and renal insufficiency ( P < 0.01 for each ) but not with smoking status , body mass index , ejection fraction , troponin I or C-reactive protein . After adjustment for differences in baseline characteristics , ECG changes , troponin I , and C-reactive protein , an MCP-1 level > 75th percentile ( corresponding to the 90th percentile in the healthy volunteers ) was associated with an increased risk of death or myocardial infa rct ion through 10 months of follow-up ( adjusted hazard ratio , 1.53 ; 95 % CI , 1.09 to 2.14;P = 0.01 ) . Conclusions —In a large cohort of patients with acute coronary syndromes , an elevated baseline level of MCP-1 was associated both with traditional risk factors for atherosclerosis as well as an increased risk for death or myocardial infa rct ion , independent of baseline variables . Because it appears to play a crucial role at multiple stages of atherosclerosis , MCP-1 is attractive as a surrogate biomarker and merits further study as a potential therapeutic target AIMS Previous studies have shown an abnormal expression of cellular adhesion molecules and cytokines in chronic heart failure , which may be related to endothelial dysfunction characterizing this syndrome . Our study investigates the effects of physical training on serum activity of some peripheral inflammatory markers associated with endothelial dysfunction , such as granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , macrophage chemoattractant protein-1 ( MCP-1 ) , soluble intercellular adhesion molecule-1 ( sICAM-1 ) and soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) in patients with chronic heart failure . METHODS AND RESULTS Serum levels of GM-CSF , MCP-1 , sICAM-1 and sVCAM-1 were determined in 12 patients with stable chronic heart failure ( ischaemic heart failure : 6/12 , dilated cardiomyopathy : 6/12 , New York Heart Association : II-III , ejection fraction : 24+/-2 % ) before and after a 12-week programme of physical training in a r and omized crossover design . In addition , the functional status of chronic heart failure patients was evaluated by using a cardiorespiratory exercise stress test to measure peak oxygen consumption . Physical training produced a significant reduction in serum GM-CSF ( 28+/-2 vs 21+/-2 pg . ml(-1 ) , P<0.001 ) , MCP-1 ( 192+/-5 vs 174+/-6 pg . ml(-1 ) , P<0.001 ) , sICAM-1 ( 367+/-31 vs 314+/-29 ng . ml(-1 ) , P<0.01 ) and sVCAM-1 ( 1247+/-103 vs 1095+/-100 ng . ml(-1 ) , P<0.01 ) as well as a significant increase in peak oxygen consumption ( 14.6+/-0.5 vs 16.5+/-0.5 ml . kg(-1)min(-1 ) , P<0.005 ) . A significant correlation was found between the training-induced improvement in peak oxygen consumption and percentage reduction in soluble adhesion molecules sICAM-1 ( r=-0.72 , P<0.01 ) and sVCAM-1 ( r=-0.67 , P<0.02 ) . CONCLUSION Physical training affects beneficially peripheral inflammatory markers reflecting monocyte/macrophage-endothelial cell interaction . Training-induced improvement in exercise tolerance is correlated with the attenuation of the inflammatory process , indicating that inflammation may contribute significantly to the impaired exercise capacity seen in chronic heart failure INTRODUCTION The biological mechanisms through which increased physical activity or structured exercise training lowers the risk of recurrent cardiac events are incompletely understood . We examined the extent to which modification of primary risk markers explains the association between physical activity and cardiovascular death in participants with diagnosed cardiovascular disease ( CVD ) . METHODS AND RESULTS In a prospect i ve study of 1429 participants with physician-diagnosed CVD living in Engl and and Scotl and ( age = 66.5 ± 11.1 yr ( mean ± SD ) , 54.2 % men ) , we measured physical activity and several risk markers ( body mass index , total-to-HDL cholesterol ratio , diagnosed diabetes , systolic blood pressure , resting heart rate , C-reactive protein ) at baseline . The main outcome was CVD death . There were a total of 446 all-cause deaths during an average of 7.0 ± 3.1 yr of follow-up , of which 213 were attributed to cardiovascular causes . Participation in moderate to vigorous physical activity at least three sessions per week was associated with lower risk of CVD death ( hazard ratio = 0.61 , 95 % confidence interval = 0.38 - 0.98 ) . Physically active participants demonstrated significantly lower levels of body mass index , diabetes , and inflammatory risk ( C-reactive protein ) . Metabolic ( body mass index , total-to-HDL cholesterol ratio , and physician-diagnosed diabetes ) and inflammatory risk factors explained an estimated 12.8 % and 15.4 % , respectively , of the association between physical activity and CVD death . CONCLUSIONS Physical activity may reduce the risk of secondary CVD events , in part , by improving metabolic and inflammatory risk markers Objective : To determine whether cardiac rehabilitation influences plasma levels of angiogenic cytokines and their correlation with myocardial blood flow ( MBF ) . Design : R and omised controlled study . Setting : Tertiary cardiac centre . Patients : 39 postinfa rct ion patients r and omised to either a 3-month training group ( n = 20 ) or a non-training group ( n = 19 ) , and 19 normal controls . Interventions : Cardiac rehabilitation . Main outcome measures : MBF by cardiac magnetic resonance imaging , and plasma levels of stem cell factor ( SCF ) , stromal-derived factor-1 ( SDF-1 ) , and vascular endothelial growth factor ( VEGF ) measured at enrolment and at 3 months after r and omisation . Results : At baseline , when compared with the healthy subjects , postinfa rct ion patients had a lower MBF in the infa rct ed myocardium during dipyridamole-induced stress ( 1.65 ( 0.58 ) vs 2.77 ( 0.78 ) ml/min/g , p<0.001 ) but higher plasma levels of VEGF ( 3.65 ( 0.75 ) vs 2.77 ( 0.59 ) pg/ml , p<0.001 expressed as the natural logarithm ) and SDF-1 ( 2113 ( 345 ) vs 1869 ( 309 ) pg/ml , p = 0.009 ) . Only SDF-1 was inversely associated with stress MBF in both remote ( r = −0.39 , p = 0.03 ) and infa rct ed myocardium ( r = −0.62 , p<0.001 ) . After 3 months , the training group ’s stress MBF had increased by 33 % in the remote ( p<0.001 ) and 28 % in infa rct ed myocardium ( p = 0.02 ) , while VEGF decreased by 9 % ( p = 0.01 ) , and SDF-1 decreased by 11 % ( p = 0.02 ) . The change in SDF-1 was inversely correlated with the change in stress MBF in both remote ( r = −0.40 , p = 0.01 ) and infa rct ed myocardium ( r = −0.50 , p = 0.001 ) . In the non-training group , MBF and cytokines were unchanged . Conclusion : Cardiac rehabilitation improves stress MBF in postinfa rct ion patients , with an inverse decrease in circulating angiogenic cytokines Background / Objectives : Lifestyle habits , vascular function and inflammation are components in the development of cardiovascular disease ( CVD ) . We investigated whether simple advice on dietary and exercise habits given ( at a single time point ) to hypercholesterolemic men affects circulating biomarkers of inflammation and vascular adhesion . Subjects/ Methods : In total , 157 men ( age 46±5 years ) with mild hypercholesterolemia were r and omized to four intervention groups , diet ( D , n=40 ) , exercise ( E , n=39 ) , diet and exercise ( DE , n=39 ) or controls ( C , n=39 ) and serum concentrations of C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , soluble intercellular adhesion molecule 1 ( sICAM-1 ) , soluble vascular cell adhesion molecule 1 ( sVCAM-1 ) and soluble E-selectin ( sE-selectin ) were quantified at baseline and after a 6-month intervention period . Results : The intervention applied in this study , that is , simple advice on lifestyle changes given at a single time point , had a modest effect on inflammatory biomarkers and soluble vascular adhesion molecules . The most apparent alterations were found for individuals in group DE , who responded with significant reductions in sICAM-1 , −28 ( −41 to −14 μg/l ) and sE-selectin , −3.6 ( −6.9 to −0.3 μg/l ) after 6 months . None of the groups had altered their concentrations of sVCAM-1 , CRP or IL-6 significantly after the intervention . In all individuals combined , we found changes in apolipoprotein B ( apoB ) to predict alterations in sICAM-1 ( β=0.21 ) and sE-selectin ( β=0.26 ) , independently of changes in inflammation and other adhesion molecules . Conclusions : These observations indicate that even small efforts to improve diet and physical activity can influence biomarkers of vascular function in individuals at increased risk for CVD . ApoB was identified as an important determinant of this improvement , which adds further support to the notion of apoB as a critical target in cardiovascular prevention BACKGROUND Supervised exercise training ( SET ) is recommended as initial treatment to improve walking capacity in peripheral arterial disease ( PAD ) patients with intermittent claudication . Various mechanisms by which SET yields beneficial effects are postulated , however data regarding its influence on angiogenesis are scarce . Thus , we design ed a prospect i ve r and omized controlled trial to study the impact of SET on markers of angiogenesis and endothelial function in PAD . METHODS Forty PAD patients were r and omized to SET on top of best medical treatment ( SET+BMT ) for 6 months versus best medical treatment ( BMT ) only . Endothelial progenitor cells ( EPC ) were assessed by whole-blood flow cytometry ( co-expression of CD34 + CD133 + KDR+ ) and cell culture assays ( endothelial cell-colony forming units , circulating angiogenic cells , migration assay ) at baseline , 3 , 6 and 12-months after inclusion . Changes of plasma levels of asymmetric dimethylarginine ( ADMA ) , vascular endothelial growth factor ( VEGF ) , stromal cell-derived factor-1 ( SDF-1 ) and maximum walking distance were determined . RESULTS EPC - measured by flow cytometric and cell culture techniques - increased significantly upon training paralleled by a significant decrease of ADMA when compared to the BMT group ( p<0.05 ) . Six months after training cessation , the beneficial effect of SET on EPC diminished , but maximum walking distance was significantly improved compared to baseline and controls ( p<0.05 ) . No significant changes were observed for VEGF and SDF-1 plasma levels in time course . CONCLUSIONS SET increases circulating EPC counts and decreases ADMA levels reflecting enhanced angiogenesis and improved endothelial function , which might contribute to cardiovascular risk reduction Inflammatory pathways are involved in destabilization of atherosclerotic plaques . We assessed the hypothesis that endurance training decreases circulating concentrations of inflammatory markers in persons with coronary artery disease ( CAD ) and cardiovascular risk factors ( CVRFs ) . Thirty-two subjects with CAD and /or CVRFs joined a 12-week supervised endurance training . We found a significant decrease of the chemokines interleukin (IL)-8 ( pre : 3.9+/-0.6 , change : -1.2+/-0.4 pg/ml , -21 % , p=0.002 ) and monocyte chemoattractant protein-1 ( pre : 213+/-9 , change : -20.4+/-8.2 pg/ml , -5 % , p=0.03 ) . Diabetes mellitus ( DM ) significantly influenced changes of IL-8 ( p=0.002 ) . IL-8 substantially dropped by 39 % in diabetics . Moreover , matrix metalloproteinase-9 ( MMP-9 ) highly significantly decreased in response to training ( pre : 750+/-98 , change : -278+/-77 ng/ml , -18 % , p=0.005 ) . Exercise-induced changes of MMP-9 were influenced by concomitant use of statins ( p=0.038 ) . We observed a particularly strong MMP-9 reduction of 44 % in patients treated with statins . Acute phase reactants IL-6 ( pre : 1.7+/-0.3 , change : + 0.25+/-0.7 pg/ml , + 4 % , p=0.58 ) and high sensitivity C-reactive protein ( pre : 2.1+/-0.5 , change : -0.25+/-0.4 mg/l , -9 % , p=0.54 ) did not change in response to training . In conclusion , endurance training decreased circulating chemokines and MMP-9 , which may in part explain its beneficial effect on coronary risk . Patients with DM or treated with statins because of hypercholesterolemia may particularly take advantage Obesity is associated with low- grade inflammation , insulin resistance , type 2 diabetes , and cardiovascular disease . This study investigated the effect of a 15-wk lifestyle intervention ( hypocaloric diet and daily exercise ) on inflammatory markers in plasma , adipose tissue ( AT ) , and skeletal muscle ( SM ) in 27 severely obese subjects ( mean body mass index : 45.8 kg/m2 ) . Plasma sample s , subcutaneous abdominal AT biopsies , and vastus lateralis SM biopsies were obtained before and after the intervention and analyzed by ELISA and RT-PCR . The intervention reduced body weight ( P < 0.001 ) and increased insulin sensitivity ( homeostasis model assessment ; P < 0.05 ) . Plasma adiponectin ( P < 0.001 ) increased , and C-reactive protein ( P < 0.05 ) , IL-6 ( P < 0.01 ) , IL-8 ( P < 0.05 ) , and monocyte chemoattractant protein-1 ( P < 0.01 ) decreased . AT inflammation was reduced , determined from an increased mRNA expression of adiponectin ( P < 0.001 ) and a decreased expression of macrophage-specific markers ( CD14 , CD68 ) , IL-6 , IL-8 , and tumor necrosis factor-alpha ( P < 0.01 ) . After adjusting for macrophage infiltration in AT , only IL-6 mRNA was decreased ( P < 0.05 ) . Only very low levels of inflammatory markers were found in SM . The intervention had no effect on adiponectin receptor 1 and 2 mRNA in AT or SM . Thus hypocaloric diet and increased physical activity improved insulin sensitivity and reduced low- grade inflammation . Markers of inflammation were particularly reduced in AT , whereas SM does not contribute to this attenuation of whole body inflammation |
2,214 | 27,873,225 | An inverse exponential relationship was found and fitted between the ratio ( ∆QALY/∆LE ) and ∆HbA1c .
Conclusion There is a consistent relationship between ∆HbA1c and ∆QALYs or ∆LE in cost-effectiveness analyses using type 2 diabetes simulation models . | Background There are an increasing number of studies using simulation models to conduct cost-effectiveness analyses for type 2 diabetes mellitus .
Objective To evaluate the relationship between improvements in glycosylated haemoglobin ( HbA1c ) and simulated health outcomes in type 2 diabetes cost-effectiveness studies . | Background The aim of this study was to project health-economic outcomes relevant to the German setting for the addition of pioglitazone to existing treatment regimens in patients with type 2 diabetes , evidence of macrovascular disease and at high risk of cardiovascular events . Methods Event rates corresponding to macrovascular outcomes from the Prospect i ve Pioglitazone Clinical Trial in Macrovascular Events ( PROactive ) study of pioglitazone were used with a modified version of the CORE Diabetes Model to simulate outcomes over a 35-year time horizon . Direct medical costs were accounted from a healthcare payer perspective in year 2005 values . Germany specific costs were applied for patient treatment , hospitalization and management . Both costs and clinical benefits were discounted at 5.0 % per annum . Results Over patient lifetimes pioglitazone treatment improved undiscounted life expectancy by 0.406 years and improved quality -adjusted life expectancy by 0.120 quality -adjusted life years ( QALYs ) compared to placebo . Direct medical costs ( treatment plus complication costs ) were marginally higher for pioglitazone treatment and calculation of the incremental cost-effectiveness ratio ( ICER ) produced a value of € 13,294 per QALY gained with the pioglitazone regimen versus placebo . Acceptability curve analysis showed that there was a 78.2 % likelihood that pioglitazone would be considered cost-effective in Germany , using a " good value for money " threshold of € 50,000 per QALY gained . Sensitivity analyses showed that the results were most sensitive to changes in the simulation time horizon . After adjustment for the potential stabilization of pancreatic β-cell function with pioglitazone treatment , the ICER was € 6,667 per QALY gained for pioglitazone versus placebo . Conclusion The findings of this modelling analysis indicated that , for patients with a history of macrovascular disease , addition of pioglitazone to existing therapy reduces the long-term cumulative incidence of diabetes-complications at a cost that would be considered to represent good value for money in the German setting OBJECTIVES The aim of this study is to examine the cost-effectiveness of a group-based peer support intervention in general practice for patients with type 2 diabetes . METHODS Incremental cost utility analysis combining within trial and beyond trial components to compare the lifetime costs and benefits of alternative strategies : CONTROL st and ardized diabetes care ; INTERVENTION group-based peer support in addition to st and ardized diabetes care . Within trial analysis was based on a cluster r and omized controlled trial of 395 patients with type 2 diabetes in the east of Irel and . Beyond trial analysis was conducted using the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) Outcomes Model . Uncertainty was explored using a range of sensitivity analyses and cost-effectiveness acceptability curves were generated . RESULTS Compared with the control strategy , the intervention was associated with an increase of 0.09 ( 95 percent confidence interval [ CI ] , -0.05 to 0.25 ) in mean quality -adjusted life-years per patient and savings of € 637.43 ( 95 percent CI , -2455.19 to 1125.45 ) in mean healthcare cost per patient and € 623.39 ( 95 percent CI , -2507.98 to 1298.49 ) in mean total cost per patient respectively . The likelihood of the intervention being cost-effective was appreciably higher than 80 percent for a range of potential willingness-to-pay cost-effectiveness thresholds . CONCLUSIONS Our results suggest that while a group-based peer support intervention shows a trend toward improved risk factor management , we found no significant differences in final cost or effectiveness endpoints between intervention and control . The probabilistic results suggest that the intervention was more cost-effective , with probability values of higher than 80 percent across a range of potential cost-effectiveness threshold values Background : The benefits of self-monitoring blood glucose levels are unclear in patients with type 2 diabetes mellitus who do not use insulin , but there are considerable costs . We sought to determine the cost effectiveness of self-monitoring for patients with type 2 diabetes not using insulin . Methods : We performed an incremental cost-effectiveness analysis of the self-monitoring of blood glucose in adults with type 2 diabetes not taking insulin . We used the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) model to forecast diabetes-related complications , corresponding quality -adjusted life years and costs . Clinical data were obtained from a systematic review comparing self-monitoring with no self-monitoring . Costs and utility decrements were derived from published sources . We performed sensitivity analyses to examine the robustness of the results . Results : Based on a clinical ly modest reduction in hemoglobin A1C of 0.25 % ( 95 % confidence interval 0.15–0.36 ) estimated from the systematic review , the UKPDS model predicted that self-monitoring performed 7 or more times per week reduced the lifetime incidence of diabetes-related complications compared with no self-monitoring , albeit at a higher cost ( incremental cost per quality -adjusted life year $ 113 643 ) . The results were largely unchanged in the sensitivity analysis , although the incremental cost per quality -adjusted life year fell within widely cited cost-effectiveness thresholds when testing frequency or the price per test strip was substantially reduced from the current levels . Interpretation : For most patients with type 2 diabetes not using insulin , use of blood glucose test strips for frequent self-monitoring ( ≥ 7 times per week ) is unlikely to represent efficient use of finite health care re sources , although periodic testing ( e.g. , 1 or 2 times per week ) may be cost-effective . Reduced test strip price would likely also improve cost-effectiveness OBJECTIVE —The efficacy and safety of adding liraglutide ( a glucagon-like peptide-1 receptor agonist ) to metformin were compared with addition of placebo or glimepiride to metformin in subjects previously treated with oral antidiabetes ( OAD ) therapy . RESEARCH DESIGN AND METHODS —In this 26-week , double-blind , double-dummy , placebo- and active-controlled , parallel-group trial , 1,091 subjects were r and omly assigned ( 2:2:2:1:2 ) to once-daily liraglutide ( either 0.6 , 1.2 , or 1.8 mg/day injected subcutaneously ) , to placebo , or to glimepiride ( 4 mg once daily ) . All treatments were in combination therapy with metformin ( 1 g twice daily ) . Enrolled subjects ( aged 25–79 years ) had type 2 diabetes , A1C of 7–11 % ( previous OAD monotherapy for ≥3 months ) or 7–10 % ( previous OAD combination therapy for ≥3 months ) , and BMI ≤40 kg/m2 . RESULTS —A1C values were significantly reduced in all liraglutide groups versus the placebo group ( P < 0.0001 ) with mean decreases of 1.0 % for 1.8 mg liraglutide , 1.2 mg liraglutide , and glimepiride and 0.7 % for 0.6 mg liraglutide and an increase of 0.1 % for placebo . Body weight decreased in all liraglutide groups ( 1.8–2.8 kg ) compared with an increase in the glimepiride group ( 1.0 kg ; P < 0.0001 ) . The incidence of minor hypoglycemia with liraglutide ( ∼3 % ) was comparable to that with placebo but less than that with glimepiride ( 17 % ; P < 0.001 ) . Nausea was reported by 11–19 % of the liraglutide-treated subjects versus 3–4 % in the placebo and glimepiride groups . The incidence of nausea declined over time . CONCLUSIONS —In subjects with type 2 diabetes , once-daily liraglutide induced similar glycemic control , reduced body weight , and lowered the occurrence of hypoglycemia compared with glimepiride , when both had background therapy of metformin BACKGROUND AND OBJECTIVES Exenatide , a GLP-1 receptor agonist for adjuvant treatment of type 2 diabetes mellitus ( T2DM ) , has been shown to be as effective as insulin glargine ( IG ) for reducing glycated hemoglobin levels combined with metformin or/ and sulphonylureas . Exenatide is associated to weight reduction and a higher incidence of gastrointestinal adverse events . The objective of this study was to assess the cost-effectiveness of exenatide as compared to IG in obese patients with T2DM not achieving an adequate blood glucose control from the perspective of the Spanish healthcare system . METHODS Pharmacoeconomic model inputs were obtained from an obese sub population ( BMI ≥ 30 k/m(2 ) ) of an international , r and omized , controlled clinical trial comparing exenatide with IG in poorly controlled T2DM patients , and were supplemented with country-specific data . RESULTS Exenatide was associated to improvements in life-years gained and quality -adjusted life years ( QALYs ) by 0.11 and 0.62 respectively versus IG . Direct costs were € 9,306 higher as compared to IG ( € 47,010 versus € 37,704 , with increased pharmacy costs as the main driver ) . Exenatideís incremental cost-effectiveness ratio was € 15,068 per QALY gained versus IG . CONCLUSIONS Exenatide was associated to greater clinical benefits and higher costs in obese T2DM patients as compared to IG . Considering a willingness-to-pay threshold of € 30,000 per QALY gained in the Spanish setting , exenatide represents an efficient option in comparison with IG OBJECTIVES This analysis provides an early estimate of the cost-effectiveness of adjunctive exenatide in treating type 2 diabetes mellitus in the United States . Data from pivotal phase III 30-week clinical trials and 52 weeks of their subsequent open-label extension studies ( i.e. , 82 weeks total ) were used to project the effects of 30 years of adjunctive exenatide treatment . METHODS This analysis utilized a published and vali date d Markov model incorporating Monte Carlo simulation with tracker variables to estimate the clinical and cost outcomes of adding exenatide to a background of metformin and /or sulfonylurea treatment , with the effects of 30 years of adjunctive exenatide treatment ( projected from data from 82 weeks of exenatide treatment ) compared with no additional treatment beyond metformin and /or a sulfonylurea . Sensitivity analyses were performed on key clinical assumptions , discount rates , and shorter time horizons . RESULTS The base-case scenario ( 30 years of exenatide ) yielded an incremental cost-effectiveness ratio ( ICER ) of $ 35,571 . We found that shortening the time horizons and removing the lipid effects of exenatide had the greatest negative impact on ICERs when performing sensitivity analysis . CONCLUSIONS Our analysis demonstrated that exenatide used for 20 or 30 years compared with no additional treatment beyond metformin and /or a sulfonylurea is cost-effective in the adjunctive treatment of type 2 diabetes with an ICER less than $ 50,000 per life-year gained . Sensitivity analyses suggest that , in addition to sustained reduction in HbA(1c ) , the added clinical effects of improved lipid values , systolic blood pressure , and reduced body mass index all positively contributed to the cost-effectiveness of exenatide OBJECTIVE To develop and vali date a comprehensive computer simulation model to assess the impact of screening , prevention , and treatment strategies on type 2 diabetes and its complications , comorbidities , quality of life , and cost . RESEARCH DESIGN AND METHODS The incidence of type 2 diabetes and its complications and comorbidities were derived from population -based epidemiologic studies and r and omized , controlled clinical trials . Health utility scores were derived for patients with type 2 diabetes using the Quality of Well Being-Self-Administered . Direct medical costs were derived for managed care patients with type 2 diabetes using paid insurance cl aims . Monte Carlo techniques were used to implement a semi-Markov model . Performance of the model was assessed using baseline and 4- and 10-year follow-up data from the older-onset diabetic population studied in the Wisconsin Epidemiologic Study of Diabetic Retinopathy ( WESDR ) . RESULTS Applying the model to the baseline WESDR population with type 2 diabetes , we predicted mortality to be 51 % at 10 years . The prevalences of stroke and myocardial infa rct ion were predicted to be 18 and 19 % at 10 years . The prevalences of nonproliferative diabetic retinopathy , proliferative retinopathy , and macular edema were predicted to be 45 , 16 , and 18 % , respectively ; the prevalences of microalbuminuria , proteinuria , and end-stage renal disease were predicted to be 19 , 39 , and 3 % , respectively ; and the prevalences of clinical neuropathy and amputation were predicted to be 52 and 5 % , respectively , at 10 years . Over 10 years , average undiscounted total direct medical costs were estimated to be USD $ 53,000 per person . Among survivors , the average utility score was estimated to be 0.56 at 10 years . CONCLUSIONS Our computer simulation model accurately predicted survival and the cardiovascular , microvascular , and neuropathic complications observed in the WESDR cohort with type 2 diabetes over 10 years . The model can be used to predict the progression of diabetes and its complications , comorbidities , quality of life , and cost and to assess the relative effectiveness , cost-effectiveness , and cost-utility of alternative strategies for the prevention and treatment of type 2 diabetes Aims /hypothesisThe aim of this study was to develop a simulation model for Type 2 diabetes that can be used to estimate the likely occurrence of major diabetes-related complications over a lifetime , in order to calculate health economic outcomes such as quality -adjusted life expectancy . Methods Equations for forecasting the occurrence of seven diabetes-related complications and death were estimated using data on 3642 patients from the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) . After examining the internal validity , the UKPDS Outcomes Model was used to simulate the mean difference in expected quality -adjusted life years between the UKPDS regimens of intensive and conventional blood glucose control . Results The model ’s forecasts fell within the 95 % confidence interval for the occurrence of observed events during the UKPDS follow-up period . When the model was used to simulate event history over patients ’ lifetimes , those treated with a regimen of conventional glucose control could expect 16.35 undiscounted quality -adjusted life years , and those receiving treatment with intensive glucose control could expect 16.62 quality -adjusted life years , a difference of 0.27 ( 95 % CI : −0.48 to 1.03 ) . Conclusions /interpretationsThe UKPDS Outcomes Model is able to simulate event histories that closely match observed outcomes in the UKPDS and that can be extrapolated over patients ’ lifetimes . Its validity in estimating outcomes in other groups of patients , however , remains to be evaluated . The model allows simulation of a range of long-term outcomes , which should assist in informing future economic evaluations of interventions in Type 2 diabetes A definitive model for predicting absolute risk of coronary heart disease ( CHD ) in male and female people with Type II diabetes is not yet available . This paper provides an equation for estimating the risk of new CHD events in people with Type II diabetes , based on data from 4540 U.K. Prospect i ve Diabetes Study male and female patients . Unlike previously published risk equations , the model is diabetes-specific and incorporates glycaemia , systolic blood pressure and lipid levels as risk factors , in addition to age , sex , ethnic group , smoking status and time since diagnosis of diabetes . All variables included in the final model were statistically significant ( P<0.001 , except smoking for which P=0.0013 ) in likelihood ratio testing . This model provides the estimates of CHD risk required by current guidelines for the primary prevention of CHD in Type II diabetes BACKGROUND Improved blood-glucose control decreases the progression of diabetic microvascular disease , but the effect on macrovascular complications is unknown . There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation . We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a r and omised controlled trial . METHODS 3867 newly diagnosed patients with type 2 diabetes , median age 54 years ( IQR 48 - 60 years ) , who after 3 months ' diet treatment had a mean of two fasting plasma glucose ( FPG ) concentrations of 6.1 - 15.0 mmol/L were r and omly assigned intensive policy with a sulphonylurea ( chlorpropamide , glibenclamide , or glipizide ) or with insulin , or conventional policy with diet . The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group , the aim was the best achievable FPG with diet alone ; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment : any diabetes-related endpoint ( sudden death , death from hyperglycaemia or hypoglycaemia , fatal or non-fatal myocardial infa rct ion , angina , heart failure , stroke , renal failure , amputation [ of at least one digit ] , vitreous haemorrhage , retinopathy requiring photocoagulation , blindness in one eye , or cataract extraction ) ; diabetes-related death ( death from myocardial infa rct ion , stroke , peripheral vascular disease , renal disease , hyperglycaemia or hypoglycaemia , and sudden death ) ; all-cause mortality . Single clinical endpoints and surrogate sub clinical endpoints were also assessed . All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy . FINDINGS Over 10 years , haemoglobin A1c ( HbA1c ) was 7.0 % ( 6.2 - 8.2 ) in the intensive group compared with 7.9 % ( 6.9 - 8.8 ) in the conventional group -- an 11 % reduction . There was no difference in HbA1c among agents in the intensive group . Compared with the conventional group , the risk in the intensive group was 12 % lower ( 95 % CI 1 - 21 , p=0.029 ) for any diabetes-related endpoint ; 10 % lower ( -11 to 27 , p=0.34 ) for any diabetes-related death ; and 6 % lower ( -10 to 20 , p=0.44 ) for all-cause mortality . Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25 % risk reduction ( 7 - 40 , p=0.0099 ) in microvascular endpoints , including the need for retinal photocoagulation . There was no difference for any of the three aggregate endpoints between the three intensive agents ( chlorpropamide , glibenclamide , or insulin ) . Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis ( both p<0.0001 ) . The rates of major hypoglycaemic episodes per year were 0.7 % with conventional treatment , 1.0 % with chlorpropamide , 1.4 % with glibenclamide , and 1.8 % with insulin . Weight gain was significantly higher in the intensive group ( mean 2.9 kg ) than in the conventional group ( p<0.001 ) , and patients assigned insulin had a greater gain in weight ( 4.0 kg ) than those assigned chlorpropamide ( 2.6 kg ) or glibenclamide ( 1.7 kg ) . INTERPRETATION Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications , but not macrovascular disease , in patients with type 2 diabetes . ( ABSTRACT TRUNCATED Abstract Background : The lack of adequate glycaemic control for patients with type 2 diabetes mellitus ( T2DM ) , especially with existing second-line therapies , represents an unmet medical need . Of the newer therapies , the incretin-based medicines , such as saxagliptin , look promising to consoli date second-line pharmacotherapy . Objective : This study evaluates the long-term economic consequences of saxagliptin versus sulfonylurea ( glipizide ) as second-line therapy when used in combination with metformin after failure of monotherapy treatment with metformin , in patients with T2DM in Germany . Methods : A published discrete event simulation model with a fixed-time increment was used to model the effects of different treatment scenarios over a 40-year ( life- ) time horizon . Disease progression was modelled using evidence from the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) 68 . The treatment sequence matched that of published German guidelines , and efficacy and safety data were derived from published sources . The model assumes that quality -adjusted life-years ( QALYs ) are affected by complications , hypoglycaemic events and weight change over a lifetime . Costs were specific to the German setting , where sulfonylureas are generic . Costs and effects were discounted annually at 3 % . The extended perspective of the national sick funds was adopted , and recommendations from the Institute for Quality and Efficiency in Health Care ( IQWiG ) were considered . Results : In the base-case analysis , treatment with saxagliptin plus metformin was associated with a lower incidence of both symptomatic and severe hypoglycaemic events , result ing in an incremental benefit of 0.12 QALYs and an incremental cost-effectiveness ratio ( ICER ) of € 13 931 per QALY gained compared with sulfonylurea plus metformin ( year of costing 2009 ) . Modest reductions in all macro- and microvascular complications were seen in those receiving saxagliptin plus metformin compared with sulfonylurea plus metformin . Sensitivity analysis showed that treatment-related weight changes , as a risk factor for complications , represent the most influential driver of cost effectiveness . Conclusion : The study demonstrated improved outcomes with saxagliptin at a cost that would likely be considered acceptable in the German setting . Furthermore , the findings of the sensitivity analysis suggest that the results are robust to various assumptions concerning input variables and modelling assumptions Background Canadian patients , healthcare providers and payers share interest in assessing the value of self-monitoring of blood glucose ( SMBG ) for individuals with type 2 diabetes but not on insulin . Using the UKPDS ( UK Prospect i ve Diabetes Study ) model , the Canadian Optimal Prescribing and Utilization Service ( COMPUS ) conducted an SMBG cost-effectiveness analysis . Based on the results , COMPUS does not recommend routine strip use for most adults with type 2 diabetes who are not on insulin . Cost-effectiveness studies require many assumptions regarding cohort , clinical effect , complication costs , etc . The COMPUS evaluation included several conservative assumptions that negatively impacted SMBG cost effectiveness . Objectives Current objectives were to ( i ) review key , impactful COMPUS assumptions ; ( ii ) illustrate how alternative inputs can lead to more favourable results for SMBG cost effectiveness ; and ( iii ) provide recommendations for assessing its long-term value . Methods A summary of COMPUS methods and results was followed by a review of assumptions ( for trial-based glycosylated haemoglobin [ HbA1c ] effect , patient characteristics , costs , simulation pathway ) and their potential impact . The UKPDS model was used for a 40-year cost-effectiveness analysis of SMBG ( 1.29 strips per day ) versus no SMBG in the Canadian payer setting . COMPUS assumptions for patient characteristics ( e.g. HbA1c 8.4 % ) , SMBG HbA1c advantage ( −0.25 % ) and costs were retained . As with the COMPUS analysis , UKPDS HbA1c decay curves were incorporated into SMBG and no-SMBG pathways . An important difference was that SMBG HbA1c benefits in the current study could extend beyond the initial simulation period . Sensitivity analyses examined SMBG HbA1c advantage , adherence , complication history and cost inputs . Outcomes ( discounted at 5 % ) included QALYs , complication rates , total costs ( year 2008 values ) and incremental cost-effectiveness ratios ( ICERs ) . Results The base-case ICER was $ Can63 664 per QALY gained ; approximately 56 % of the COMPUS base-case ICER . SMBG was associated with modest risk reductions ( 0.10–0.70 % ) for six of seven complications . Assuming an SMBG advantage of −0.30 % decreased the current base-case ICER by over $ Can10 000 per QALY gained . With adherence of 66 % and 87 % , ICERs were ( respectively ) $ Can39231 and $ Can54349 per QALY gained . Incorporating a more representative complication history and 15 % complication cost increase result ed in an ICER of $ Can49 743 per QALY gained . Conclusions These results underscore the importance of modelling assumptions regarding the duration of HbA1c effect . The current study shares several COMPUS limitations relating to the UKPDS model being design ed for newly diagnosed patients , and to r and omized controlled trial monitoring rates . Neither study explicitly examined the impact of varying the duration of initial HbA1c effects , or of medication or other treatment changes . Because the COMPUS research will potentially influence clinical practice and reimbursement policy in Canada , underst and ing the impact of assumptions on cost-effectiveness results seems especially important . Demonstrating that COMPUS ICERs were greatly reduced through variations in a small number of inputs may encourage additional clinical research design ed to measure SMBG effects within the context of optimal disease management . It may also encourage additional economic evaluations that incorporate lessons learned and best practice s for assessing the overall value of SMBG for type 2 diabetes in insulin-naive patients Introduction Treatment with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors , which target the incretin axis , has the potential to improve glycemic control in type 2 diabetes patients without the weight gain associated with traditional therapies . To evaluate the relative cost-effectiveness of incretin therapies , the present study aim ed to compare the long-term clinical and cost implication s associated with liraglutide and sitagliptin in type 2 diabetes patients in Spain . Methods Data were taken from a r and omized , controlled trial ( NCT00700817 ) in which adults with type 2 diabetes failing metformin monotherapy were r and omly allocated to receive either liraglutide 1.2 mg or sitagliptin 100 mg daily in addition to metformin . Long-term projections of clinical outcomes and direct costs ( 2012 EUR ) based on observed treatment effects were made using a published and vali date d type 2 diabetes model . Costs were taken from published sources . Future costs and clinical benefits were discounted at 3 % annually . Sensitivity analyses were performed . Results Liraglutide was associated with improved discounted life expectancy ( 14.05 versus 13.91 years ) and quality -adjusted life expectancy [ 9.04 versus 8.87 quality -adjusted life years ( QALYs ) ] compared to sitagliptin . Improved clinical outcomes were driven by improved glycemic control , leading to reduced incidence of diabetes-related complications , including renal disease , cardiovascular disease , ophthalmic and diabetic foot complications . Liraglutide was associated with increased direct costs of EUR 2,297 , yielding an incremental cost-effectiveness ratio of EUR 13,266 per QALY gained versus sitagliptin . Conclusions Liraglutide was projected to improve life expectancy , quality -adjusted life expectancy and reduce incidence of diabetes-related complication . Liraglutide is likely to be cost-effective versus sitagliptin from a healthcare payer perspective in Spain Objectives To assess the long term clinical and cost effectiveness of the diabetes education and self management for ongoing and newly diagnosed ( DESMOND ) intervention compared with usual care in people with newly diagnosed type 2 diabetes . Design We undertook a cost-utility analysis that used data from a 12 month , multicentre , cluster r and omised controlled trial and , using the Sheffield type 2 diabetes model , modelled long term outcomes in terms of use of therapies , incidence of complications , mortality , and associated effect on costs and health related quality of life . A further cost-utility analysis was also conducted using current “ real world ” costs of delivering the intervention estimated for a hypothetical primary care trust . Setting Primary care trusts in the United Kingdom . Participants Patients with newly diagnosed type 2 diabetes . Intervention A six hour structured group education programme delivered in the community by two professional healthcare educators . Main outcome measures Incremental costs and quality adjusted life years ( QALYs ) gained . Results On the basis of the data in the trial , the estimated mean incremental lifetime cost per person receiving the DESMOND intervention is £ 209 ( 95 % confidence interval −£704 to £ 1137 ; € 251 , −€844 to € 1363 ; $ 326 , −$1098 to $ 1773 ) , the incremental gain in QALYs per person is 0.0392 ( −0.0813 to 0.1786 ) , and the mean incremental cost per QALY is £ 5387 . Using “ real world ” intervention costs , the lifetime incremental cost of the DESMOND intervention is £ 82 ( −£831 to £ 1010 ) and the mean incremental cost per QALY gained is £ 2092 . A probabilistic sensitivity analysis indicated that the likelihood that the DESMOND programme is cost effective at a threshold of £ 20 000 per QALY is 66 % using trial based intervention costs and 70 % using “ real world ” costs . Results from a one way sensitivity analysis suggest that the DESMOND intervention is cost effective even under more modest assumptions that include the effects of the intervention being lost after one year . Conclusion Our results suggest that the DESMOND intervention is likely to be cost effective compared with usual care , especially with respect to the real world cost of the intervention to primary care trusts , with reductions in weight and smoking being the main benefits delivered Background : Insulin analogues may be associated with fewer episodes of hypoglycemia than conventional insulins . However , they are costly alternatives . We compared the cost-effectiveness of insulin analogues and conventional insulins used to treat type 1 and type 2 diabetes mellitus in adults . Methods : We conducted a cost-effectiveness evaluation of insulin analogues versus conventional insulins using the Center for Outcomes Research Diabetes Model . We compared rapid-acting analogues ( insulin aspart and insulin lispro ) with regular human insulin , and long-acting analogues ( insulin glargine and insulin detemir ) with neutral protamine Hagedorn insulin . We derived clinical information for the comparisons from meta-analyses of r and omized controlled trials . We obtained cost and utility estimates from published sources . We performed sensitivity analyses to test the robustness of our results . Results : For type 1 diabetes , insulin aspart was more effective and less costly than regular human insulin . Insulin lispro was associated with an incremental cost of Can$28 996 per quality -adjusted life-year . The incremental cost per quality -adjusted life-year was Can$87 932 for insulin glargine and Can$387 729 for insulin detemir , compared with neutral protamine Hagedorn insulin . For type 2 diabetes , insulin aspart was associated with an incremental cost of Can$22 488 per quality -adjusted life-year compared with regular human insulin . For insulin lispro , the incremental cost was Can$130 865 . Compared with neutral protamine Hagedorn insulin , insulin detemir was less effective and more costly . Insulin glargine was associated with an incremental cost of Can$642 994 per quality -adjusted life-year . The model was sensitive to changes in the effect size of hemoglobin A1c and to decrements applied to utility scores when fear of hypoglycemia was included as a factor . Interpretation : The cost-effectiveness of insulin analogues depends on the type of insulin analogue and whether the patient receiving the treatment has type 1 or type 2 diabetes . With the exception of rapid-acting insulin analogues in type 1 diabetes , routine use of insulin analogues , especially long-acting analogues in type 2 diabetes , is unlikely to represent an efficient use of finite health care re sources BACKGROUND In people with type 2 diabetes , a dipeptidyl peptidase-4 ( DPP-4 ) inhibitor is one choice as second-line treatment after metformin , with basal insulin recommended as an alternative . We aim ed to compare the efficacy , tolerability , and safety of insulin glargine and sitagliptin , a DPP-4 inhibitor , in patients whose disease was uncontrolled with metformin . METHODS In this comparative , parallel , r and omised , open-label trial , metformin-treated people aged 35 - 70 years with glycated haemoglobin A(1c ) ( HbA(1c ) ) of 7 - 11 % , diagnosis of type 2 diabetes for at least 6 months , and body-mass index of 25 - 45 kg/m(2 ) were recruited from 17 countries . Participants were r and omly assigned ( 1:1 ) to 24-week treatment with insulin glargine ( titrated from an initial subcutaneous dose of 0·2 units per kg bodyweight to attain fasting plasma glucose of 4·0 - 5·5 mmol/L ) or sitagliptin ( oral dose of 100 mg daily ) . R and omisation ( via a central interactive voice response system ) was by r and om sequence generation and was stratified by centre . Patients and investigators were not masked to treatment assignment . The primary outcome was change in HbA(1c ) from baseline to study end . Efficacy analysis included all r and omly assigned participants who had received at least one dose of study drug and had at least one on-treatment assessment of any primary or secondary efficacy variable . This trial is registered at Clinical Trials.gov , NCT00751114 . FINDINGS 732 people were screened and 515 were r and omly assigned to insulin glargine ( n=250 ) or sitagliptin ( n=265 ) . At study end , adjusted mean reduction in HbA(1c ) was greater for patients on insulin glargine ( n=227 ; -1·72 % , SE 0·06 ) than for those on sitagliptin ( n=253 ; -1·13 % , SE 0·06 ) with a mean difference of -0·59 % ( 95 % CI -0·77 to -0·42 , p<0·0001 ) . The estimated rate of all symptomatic hypoglycaemic episodes was greater with insulin glargine than with sitagliptin ( 4·21 [ SE 0·54 ] vs 0·50 [ SE 0·09 ] events per patient-year ; p<0·0001 ) . Severe hypoglycaemia occurred in only three ( 1 % ) patients on insulin glargine and one ( < 1 % ) on sitagliptin . 15 ( 6 % ) of patients on insulin glargine versus eight ( 3 % ) on sitagliptin had at least one serious treatment-emergent adverse event . INTERPRETATION Our results support the option of addition of basal insulin in patients with type 2 diabetes inadequately controlled by metformin . Long-term benefits might be expected from the achievement of optimum glycaemic control early in the course of the disease . FUNDING Sanofi Abstract Objective : This study constructed the Economic and Health Outcomes Model for type 2 diabetes mellitus ( ECHO-T2DM ) , a long-term stochastic microsimulation model , to predict the costs and health outcomes in patients with T2DM . Naturally , the usefulness of the model depends upon its predictive accuracy . The objective of this work is to present results of a formal validation exercise of ECHO-T2DM . Methods : The validity of ECHO-T2DM was assessed using criteria recommended by the International Society for Pharmacoeconomics and Outcomes Research /Society for Medical Decision Making ( ISPOR/SMDM ) . Specifically , the results of a number of clinical trials were predicted and compared with observed study end-points using a scatterplot and regression approach . An F-test of the best-fitting regression was added to assess whether it differs statistically from the identity ( 45 ° ) line defining perfect predictions . In addition to testing the full model using all of the validation study data , tests were also performed of microvascular , macrovascular , and survival outcomes separately . The validation tests were also performed separately by type of data ( used vs not used to construct the model , economic simulations , and treatment effects ) . Results : The intercept and slope coefficients of the best-fitting regression line between the predicted outcomes and corresponding trial end-points in the main analysis were −0.0011 and 1.067 , respectively , and the R2 was 0.95 . A formal F-test of no difference between the fitted line and the identity line could not be rejected ( p = 0.16 ) . The high R2 confirms that the data points are closely ( and linearly ) associated with the fitted regression line . Additional analyses identified that disagreement was highest for macrovascular end-points , for which the intercept and slope coefficients were 0.0095 and 1.225 , respectively . The R2 was 0.95 and the estimated intercept and slope coefficients were 0.017 and 1.048 , respectively , for mortality , and the F-test was narrowly rejected ( p = 0.04 ) . The sub-set of microvascular end-points showed some tendency to over-predict ( the slope coefficient was 1.095 ) , although concordance between predictions and observed values could not be rejected ( p = 0.16 ) . Limitations : Important study limitations include : ( 1 ) data availability limited one to tests based on end-of- study outcomes rather than time-varying outcomes during the studies analyzed ; ( 2 ) complex inclusion and exclusion criteria in two studies were difficult to replicate ; ( 3 ) some of the studies were older and reflect out date d treatment patterns ; and ( 4 ) the authors were unable to identify published data on re source use and costs of T2DM suitable for testing the validity of the economic calculations . Conclusions : Using conventional methods , ECHO-T2DM simulated the treatment , progression , and patient outcomes observed in important clinical trials with an accuracy consistent with other well-accepted models . Macrovascular outcomes were over-predicted , which is common in health-economic models of diabetes ( and may be related to a general over-prediction of event rates in the United Kingdom Prospect i ve Diabetes Study [ UKPDS ] Outcomes Model ) . Work is underway in ECHO-T2DM to incorporate new risk equations to improve model prediction BACKGROUND A r and omized controlled trial has shown that supervised , facility-based exercise training is effective in improving glycemic control in type 2 diabetes . However , these programs are associated with additional costs . This analysis assessed the cost-effectiveness of such programs . METHODS Analysis used data from the Diabetes Aerobic and Resistance Exercise ( DARE ) clinical trial which compared three different exercise programs ( resistance , aerobic or a combination of both ) of 6 months duration with a control group ( no exercise program ) . Clinical outcomes at 6 months were entered for individual patients into the UKPDS economic model for type 2 diabetes adapted for the Canadian context . From this , expected life-years , quality -adjusted life-years ( QALYs ) and costs were estimated for all patients within the trial . RESULTS The combined exercise program was the most expensive ( $ 40,050 ) followed by the aerobic program ( $ 39,250 ) , the resistance program ( $ 38,300 ) and no program ( $ 31,075 ) . QALYs were highest for combined ( 8.94 ) , followed by aerobic ( 8.77 ) , resistance ( 8.73 ) and no program ( 8.70 ) . The incremental cost per QALY gained for the combined exercise program was $ 4,792 compared with aerobic alone , $ 8,570 compared with resistance alone , and $ 37,872 compared with no program . The combined exercise program remained cost-effective for all scenarios considered within sensitivity analysis . CONCLUSIONS A program providing training in both resistance and aerobic exercise was the most cost-effective of the alternatives compared . Based on previous funding decisions , exercise training for individuals with diabetes can be considered an efficient use of re sources ABSTRACT Objective : The long-term cost-effectiveness of using pioglitazone plus metformin ( Actoplusmet† ) compared with rosiglitazone plus metformin ( Av and amet‡ ) in treating type 2 diabetes ( T2DM ) was assessed from a US third-party payer perspective . † Actoplusmet is a trade name of Takeda Pharmaceuticals North America , Inc. , Deerfield , IL , USA ‡ Av and amet is a trade name of GlaxoSmithKline , Research Triangle , NC , USA Research design and methods : Clinical efficacy ( change in HbA1c and lipids ) and baseline cohort parameters were extracted from a 12-month , r and omized clinical trial ( Derosa et al. , 2006 ) evaluating the efficacy and tolerability of pioglitazone versus rosiglitazone , both in addition to metformin , in adult T2DM patients with insufficient glucose control ( n = 96 ) . A Markov-based model was used to project clinical and economic outcomes over 35 years , discounted at 3 % per annum . Costs for complications were taken from published sources . Base-case assumptions were assessed through several sensitivity analyses . Main outcome measures : Outcomes included incremental life-years , quality -adjusted life-years ( QALYs ) , total direct medical costs , cumulative incidence of complications and associated costs , and incremental cost – effectiveness ratios ( ICERs ) . Results : Compared to rosiglitazone plus metformin , pioglitazone plus metformin was projected to result in a modest improvement in 0.187 quality -adjusted life-years . Over patients ’ lifetimes , total direct medical costs were projected to be marginally lower with pioglitazone plus metformin ( difference –$526 . ) , largely due to reduced CVD complication costs . While costs were higher among renal , ulcer/amputation/neuropathy , and eye complications in the pioglitazone plus metformin group , the cost savings for CVD complications outweighed their economic impact . Pioglitazone plus metformin was found to be a dominant long-term treatment strategy in the US compared to rosiglitazone plus metformin . Sensitivity analyses showed findings to be robust under almost all scenarios , including short-term time horizons , 6 % discounting , removal of individual lipid parameters , and modifications of patient cohort to more closely represent a US T2DM population . Pioglitazone plus metformin was no longer dominant with 0 % discounting , with 25 % reduction in its HbA1c effects , or with a 15 % increase in its acquisition price . Conclusions : Under a range of assumptions and study limitations around cohorts , clinical effects , and treatment patterns , this long-term analysis showed that pioglitazone plus metformin , when compared to rosiglitazone plus metformin , was a dominant treatment strategy within the US payer setting . Results were driven by the combination of modest differences in QALYs and modest savings in total complication costs over 35 years CONTEXT Several treatment interventions can reduce complications of type 2 diabetes , but their relative cost-effectiveness is not known . OBJECTIVE To estimate the incremental cost-effectiveness of intensive glycemic control ( relative to conventional control ) , intensified hypertension control , and reduction in serum cholesterol level for patients with type 2 diabetes . DESIGN , SETTING , AND PATIENTS Cost-effectiveness analysis of a hypothetical cohort of individuals living in the United States , aged 25 years or older , who were newly diagnosed as having type 2 diabetes . The results of the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) and other studies were used to create a model of disease progression and treatment patterns . Costs were based on those used in community practice s in the United States . INTERVENTIONS Insulin or sulfonylurea therapy for intensive glycemic control ; angiotensin-converting enzyme inhibitor or beta-blocker for intensified hypertension control ; and pravastatin for reduction of serum cholesterol level . MAIN OUTCOME MEASURES Cost per quality -adjusted life-year ( QALY ) gained . Costs ( in 1997 US dollars ) and QALYs were discounted at a 3 % annual rate . RESULTS The incremental cost-effectiveness ratio for intensive glycemic control is $ 41 384 per QALY ; this ratio increased with age at diagnosis from $ 9614 per QALY for patients aged 25 to 34 years to $ 2.1 million for patients aged 85 to 94 years . For intensified hypertension control the cost-effectiveness ratio is -$1959 per QALY . The cost-effectiveness ratio for reduction in serum cholesterol level is $ 51 889 per QALY ; this ratio varied by age at diagnosis and is lowest for patients diagnosed between the ages of 45 and 84 years . CONCLUSIONS Intensified hypertension control reduces costs and improves health outcomes relative to moderate hypertension control . Intensive glycemic control and reduction in serum cholesterol level increase costs and improve health outcomes . The cost-effectiveness ratios for these 2 interventions are comparable with those of several other frequently adopted health care interventions BACKGROUND AND OBJECTIVE Medical groups have invested billions of dollars in electronic medical records ( EMRs ) , but few studies have examined the cost-effectiveness of EMR-based clinical decision support ( CDS ) . This study examined the cost-effectiveness of EMR-based CDS for adults with diabetes from the perspective of the health care system . DATA SOURCES / SETTING Clinical outcome and cost data from a r and omized clinical trial of EMR-based CDS were used as inputs into a diabetes simulation model . The simulation cohort included 1,092 patients with diabetes with A1c above goal at baseline . STUDY DESIGN The United Kingdom Prospect i ve Diabetes Study Outcomes Model , a vali date d simulation model of diabetes , was used to evaluate remaining life years , quality -adjusted life years ( QALYs ) , and health care costs over patient lifetimes ( 40-year time horizon ) from the health system perspective . PRINCIPAL FINDINGS Patients in the intervention group had significantly lowered A1c ( 0.26 percent , p = .014 ) relative to patients in the control arm . Intervention costs were $ 120 ( SE = 45 ) per patient in the first year and $ 76 ( SE = 45 ) per patient in the following years . In the base case analysis , EMR-based CDS increased lifetime QALYs by 0.04 ( SE = 0.01 ) and increased lifetime costs by $ 112 ( SE = 660 ) , result ing in an incremental cost-effectiveness ratio of $ 3,017 per QALY . The cost-effectiveness of EMR-based CDS persisted in one-way , two-way , and probabilistic sensitivity analyses . CONCLUSIONS Widespread adoption of sophisticated EMR-based CDS has the potential to modestly improve the quality of care for patients with chronic conditions without substantially increasing costs to the health care system Abstract Background : Many patients with type 2 diabetes mellitus ( T2DM ) are not able to maintain adequate HbA1c control ( < 7.0 % ) , even at maximal dosage levels of one or two oral agents , and are at increased risk for diabetes-related complications . Objective : To estimate the cost-effectiveness of a once-daily GLP-1 analog Victoza [ Novo Nordisk ] versus a thiazolidinedione ( TZD ) , rosiglitazone in patients with T2DM . Both treatment groups included background therapy with glimepiride . Research design and methods : The CORE Diabetes Model ( CDM ) was used to project and compare 35-year clinical and economic outcomes associated with liraglutide 1.2 mg + glimepiride and liraglutide 1.8 mg + glimepiride versus rosiglitazone 4 mg + glimepiride . Baseline cohort characteristics ( HbA1c ( 8.4 % ) , age , duration of disease , sex , body-mass index ( BMI ) , blood pressure , and lipids ) were based on the Liraglutide Effect and Action in Diabetes-1 ( LEAD-1 ) trial . Outcomes : Primary outcomes included life expectancy ( LE ) , quality -adjusted life-years ( QALYs ) , total costs and incremental cost-effectiveness ratios ( ICERs ) . Results : When compared to rosiglitazone , liraglutide 1.2 mg and 1.8 mg increased mean LE by 0.968 and 1.041 years , and QALYs by 0.764 and 0.837 , respectively . Total lifetime costs increased by $ 26 094 for liraglutide 1.2 mg versus rosiglitazone , and by $ 47 041 for liraglutide 1.8 mg versus rosiglitazone . ICERs for liraglutide 1.2 mg versus rosiglitazone and 1.8 mg versus rosiglitazone were $ 34 147 and $ 56 190 , respectively . Conclusions : Compared to rosiglitazone 4 mg plus glimepiride , liraglutide ( particularly at the 1.2-mg dose ) plus glimepiride is a cost-effective treatment option for improving glucose control in T2DM . Limitations include the projection of short term efficacy results from r and omized control trials to longer time horizons . In addition , clinical acceptance and overall use of rosiglitazone in the treatment of diabetes has continued to fall since publication of the clinical trial upon which this modeling analyses was based OBJECTIVES The objective of this analysis was to determine the cost-effectiveness of exenatide vs. insulin glargine in patients with type 2 diabetes failing to achieve glycaemic control with oral antidiabetic agents , in the German setting , from a third-party payer perspective . METHODS Data from a published r and omized controlled trial were used in combination with a published , vali date d computer simulation model of type 2 diabetes to project clinical and cost outcomes over a time horizon of 10 years . Cost data were obtained from published literature and expert opinion . Clinical and cost outcomes were discounted at 5 % per annum . Sensitivity analyses were performed to establish key drivers and parameters . RESULTS Treatment with exenatide compared with insulin glargine was projected to be associated with improvements in life expectancy of 0.016 years and quality -adjusted life expectancy of 0.280 quality -adjusted life years ( QALYs ) , increased lifetime direct medical costs of euro 3854 ( euro 22 095 vs. euro 18 242 ) and an incremental cost-effectiveness ratio ( ICER ) of euro 13 746 per QALY . If quality of life was not taken into account , exenatide was associated with an ICER of euro 238 201 per life year gained vs. insulin glargine . Sensitivity analyses revealed that outcomes were most sensitive to changes in assumptions for (dis)utility values relating to weight change and the rate of self-monitored blood glucose testing . CONCLUSIONS Exenatide was projected to be associated with similar clinical outcomes and increased costs compared with insulin glargine . Analysis of cost-effectiveness from a third-party perspective suggests that exenatide is likely to represent good value for money in the German setting The aim of this study was to gain a preliminary indication of the long-term clinical and economic implication s of converting treatment for patients with type 2 diabetes to insulin detemir±oral hypoglycemic agents ( OHAs ) in a routine clinical practice setting in the United States . With the use of outcome data and patient characteristics reported from an ongoing prospect i ve observational trial , a vali date d computer simulation model of diabetes was used to project the clinical and cost outcomes associated with therapy conversion to insulin detemir over a 35-y period from ( 1 ) OHA only , ( 2 ) neutral protamine Hagedorn insulin (NPH)±OHA , and ( 3 ) insulin glargine±OHA . Cost-effectiveness was assessed from a third-party healthcare payer perspective for the year 2005 . Costs and clinical outcomes were discounted at a rate of 3 % . Treatment with insulin detemir±OHA was associated with increases in quality -adjusted life expectancy of 0.309 , 0.350 , and 0.333 quality -adjusted life-years ( QALYs ) versus treatment with OHA alone , NPH±OHA , and insulin glargine±OHA , respectively . Increases in pharmacy costs were partially offset by reduced complications , particularly renal complications and neuropathy . Projected incremental cost-effectiveness ratios were well within the range considered to represent good value in the United States , at $ 7412 , $ 6269 , and $ 3951 per QALY gained for treatment with Idet+-OHA versus OHA alone , NPH±OHA , and Iglarg±OHA , respectively . On the basis of preliminary evidence of short-term improvements in glycemic control and reduced hypoglycemia , therapy conversion to insulin detemir±OHA from OHA alone , NPH±OHA , or insulin glargine±OHA was projected to increase quality -adjusted life expectancy and to represent a cost-effective treatment option in the United States OBJECTIVES This study attempted to evaluate clinical outcomes and long-term cost-effectiveness of an intervention involving Community Health Workers ( CHW 's , a.k.a . promotoras de salud in Spanish ) in assisting Mexican-American diabetes type-2 patients with controlling their condition . The intervention has been carried out in Hidalgo County , TX which is situated on the U.S.-Mexico border . STUDY DESIGN The design of the study is experimental . The sample ( n = 30 ) was recruited from Mexican-American diabetes patients aged 30 or above . The intervention group received monthly visits from CHW 's , while the control group did not . METHODS Incremental lifetime health outcomes and related expenditures were calculated using the CDC Diabetes Cost-Effectiveness Model ( DCEM ) which is a probabilistic computer simulation model of disease progression and cost-effectiveness for type 2 diabetes patients . The DCEM allows projection of lifetime healthcare costs and Quality -Adjusted Life-Years ( QALYs ) . RESULTS The intervention group showed a significant improvement in glycemic control and cholesterol management after two years of intervention . The intervention is expected to reduce long-term complications , result ing in an increase in residual life-years and quality -adjusted life-years . The incremental cost-effectiveness ratio has been estimated to be $ 13,810 , which is below the level of comparable studies . CONCLUSIONS Intervention has a substantial impact on the medical costs of type 2 diabetes treatment . The estimates presented in this model may be used to analyse the cost-effectiveness of interventions involving CHW 's for type 2 diabetes ABSTRACT Background : Self-monitoring of blood glucose ( SMBG ) in type 2 diabetes patients has been shown in meta-analyses of r and omized trials to improve HbA1c by ∼0.4 % when compared to no SMBG . However , the cost of testing supplies is high , improvements in health utility due to improved glycaemic control may be possible and cost-effectiveness has not been evaluated . Methods : A peer- review ed vali date d model projected improvements in lifetime quality -adjusted life years ( QALYs ) , long-term costs and cost-effectiveness of SMBG versus no SMBG . Markov/Monte Carlo modelling simulated the progression of complications ( cardiovascular , neuropathy , renal and eye disease ) . Transition probabilities and HbA1c-dependent adjustments came from the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) and other major studies . Effects of SMBG on HbA1c came from clinical studies , meta-analyses and population studies , but can only be considered ‘ moderate ’ levels of evidence . Costs of complications were retrieved from published sources . Direct costs of diabetes complications and SMBG were projected over patient lifetimes from a UK National Health Service perspective . Outcomes were discounted at 3.5 % annually . Extensive sensitivity analyses were performed . Results : Depending on the type of diabetes treatment ( diet and exercise/oral medications/insulin ) , improvements in glycaemic control with SMBG improved discounted QALYs anywhere from 0.165 to 0.255 years , with increased total costs of £ 1013–£2564/patient , giving incremental cost-effectiveness ratios of £ 4508:£15 515/QALY gained , well within current UK willingness-to-pay limits . Results were robust under a wide range of plausible assumptions . Conclusions : Based on the moderate level of clinical evidence available to date , improvements in glycaemic control with interventions , including SMBG , can improve patient outcomes , with acceptable cost-effectiveness ratios in the UK setting ABSTRACT Objectives : The aim of this study was to evaluate the long-term clinical and economic outcomes associated with exenatide or insulin glargine , added to oral therapy in individuals with type 2 diabetes inadequately controlled with combination oral agents in the UK setting . Methods : A published and vali date d computer simulation model of diabetes was used to project long-term complications , life expectancy , quality -adjusted life expectancy and direct medical costs . Probabilities of diabetes-related complications were derived from published sources . Treatment effects and patient characteristics were extracted from a recent r and omised controlled trial comparing exenatide with insulin glargine . Simulations incorporated published quality of life utilities and UK-specific costs from 2004 . Pharmacy costs for exenatide were based on 20 , 40 , 60 , 80 and 100 % of the US value ( as no price for the UK was available at the time of analysis ) . Future costs and clinical benefits were discounted at 3.5 % annually . Sensitivity analyses were performed . Results : In the base – case analysis exenatide was associated with improvements in life expectancy of 0.057 years and in quality -adjusted life expectancy of 0.442 quality -adjusted life years ( QALYs ) versus insulin glargine . Long-term projections demonstrated that exenatide was associated with a lower cumulative incidence of most cardiovascular disease ( CVD ) complications and CVD-related death than insulin glargine . Using the range of cost values , evaluation results showed that exenatide is likely to fall in a range between dominant ( cost and life saving ) at 20 % of the US price and cost-effective ( with an ICER of £ 22 420 per QALY gained ) at 100 % of the US price , versus insulin glargine . Conclusions : Based on the findings of a recent clinical trial , long-term projections indicated that exenatide is likely to be associated with improvement in life expectancy and quality -adjusted life expectancy compared to insulin glargine . The results from this modelling analysis suggest that that exenatide is likely to represent good value for money by generally accepted st and ards in the UK setting in individuals with type 2 diabetes inadequately controlled on oral therapy OBJECTIVES To investigate the long-term clinical and economic outcomes associated with exenatide versus insulin glargine as " add-on " treatments to oral therapy in individuals with Type 2 diabetes inadequately controlled with combination oral agents in the Swiss setting . METHODS A computer simulation model of diabetes was used to project complications , life expectancy , quality -adjusted life expectancy and direct medical costs over a 35-year time horizon . Cohort characteristics and treatment effect data were derived from a 26-week r and omized clinical trial comparing exenatide and insulin glargine . Modeled treatment effects included reductions in glycosylated hemoglobin ( HbA1c ) by -0.99 % and -1.07 % and in body mass index ( BMI ) by -0.80 and + 0.55 kg/m2 with exenatide and insulin glargine respectively . Changes in systolic blood pressure and serum lipid levels were also captured . Simulations incorporated published quality of life utilities and Swiss costs from 2006 . Extensive sensitivity analyses were conducted to assess the robustness of projected outcomes . Future clinical and economic outcomes were discounted at 2.5 % per annum . RESULTS In the base-case analysis exenatide was associated with comparable life expectancy ( 11,549 years versus 11,468 years ) and an improvement in quality -adjusted life expectancy of 0.43 quality -adjusted life years ( QALYs ) versus insulin glargine over a 35-year time horizon . Exenatide was associated with a reduced cumulative incidence of most diabetes-related complications including an absolute reduction in myocardial infa rct ion by 0.28 % . Assuming an annual treatment cost of CHF 2,797.74 for exenatide , direct costs increased by CHF 8,378 per patient over the 35-year time horizon compared to insulin glargine . The result ant incremental cost-effectiveness ratio was CHF 19,450 per QALY gained for exenatide versus insulin glargine . CONCLUSIONS Exenatide was associated with comparable life expectancy and an improvement in quality -adjusted life expectancy versus insulin glargine over a 35-year time horizon . Based on current st and ards exenatide would be a cost-effective treatment alternative to insulin glargine in Switzerl and for Type 2 diabetes patients inadequately controlled on oral therapy BACKGROUND The Economic Assessment of Glycemic control and Long-term Effects of diabetes ( EAGLE ) model was developed to provide a flexible and comprehensive tool for the simulation of the long-term effects of diabetes treatment and related costs in type 1 and type 2 diabetes . METHODS EAGLE simulations are based on risk equations , which were developed using published data from several large studies including the Diabetes Control and Complications Trial , the United Kingdom Prospect i ve Diabetes Study , and the Wisconsin Epidemiological Study of Diabetic Retinopathy . Risk equations for the probability of complications ( including hypoglycemia , retinopathy , macular edema , end-stage renal disease , neuropathy , diabetic foot syndrome , myocardial infa rct ion , and stroke ) were based on regression analyses , using linear , exponential , and quadratic regression formulae . Subsequent cost calculations are made from the simulated event rates . Internal validation of the EAGLE model was completed by comparing simulated event rates with the published event rates used as the basis for the model . RESULTS EAGLE provides microsimulations of virtual patient cohorts for type 1 and type 2 diabetes over n years in 1-year cycles . Complications include microvascular and macrovascular events and death , which are calculated over time as cumulative incidences . Glycosylated hemoglobin levels over time are simulated in relation to treatment regimen . Internal validation demonstrated that each mean event rate simulated by EAGLE overlapped with the published mean event ( within a range of + /-10 % ) . CONCLUSIONS The EAGLE model is an evidence -based , internally valid tool for the assessment of the long-term effects of diabetes treatment and related costs AIM To evaluate the cost-effectiveness of laparoscopic adjustable gastric b and ing ( LAGB ) versus st and ard medical management ( SMM ) in obese patients with type 2 diabetes from a UK healthcare payer perspective . METHODS A vali date d computer model of diabetes was used to project outcomes reported from a r and omized clinical trial of LAGB versus SMM in obese patients with type 2 diabetes . Two-year follow-up data from the trial were projected over a 40-year time horizon and cost-effectiveness was assessed from the perspective of the National Health Service . Future costs and clinical outcomes were discounted at 3.5 % annually and all costs were reported in 2010 pounds sterling . A series of sensitivity analyses were performed . RESULTS LAGB was associated with benefits in HbA1c , systolic blood pressure , body mass index and serum lipid concentrations , which led to significant increases in discounted life expectancy ( an increase of 0.64 years ) and quality -adjusted life expectancy ( an increase of 0.92 quality -adjusted life years , QALYs ) and reduced incidence of diabetes complications relative to SMM . Treatment costs in the LAGB arm increased by 4552 Great British Pounds ( GBP ) , but this was partially offset by cost savings result ing from a reduction in the incidence of all modelled diabetes complications . The incremental cost-effectiveness ratio of GBP 3602 per QALY in the base case fell well below commonly quoted willingness-to-pay thresholds in the UK setting . CONCLUSIONS On the basis of data from a recent r and omized controlled trial , LAGB is likely to be considered cost-effective from the healthcare payer perspective when compared with SMM of obesity in patients with type 2 diabetes in the UK setting Abstract Aim : To evaluate the cost-effectiveness of insulin detemir vs. NPH insulin once daily , in patients with type 2 diabetes in the Swedish setting based on clinical data from a published r and omized controlled trial . Methods : Projections of long-term outcomes were made using the IMS CORE Diabetes Model ( CDM ) , based on clinical data from a 26-week r and omized controlled trial that compared once daily insulin detemir and NPH insulin , when used to intensify insulin treatment in 271 patients with type 2 diabetes and body mass index ( BMI ) 25–40 kg/m2 . Trial results showed that insulin detemir was associated with a significantly lower incidence of hypoglycemic events and significantly less weight gain in comparison with NPH insulin . The analysis was conducted from a third party payer perspective and the base case analysis was performed over a time horizon of 40 years and future costs and clinical outcomes were discounted at a rate of 3 % per year . Results : Insulin detemir was associated with higher mean ( SD ) quality -adjusted life expectancy ( 5.42 [ 0.10 ] vs. 5.31 [ 0.10 ] quality -adjusted life years [ QALYs ] ) and lower overall costs ( SEK 378,539 [ 10,372 ] vs. SEK 384,216 [ 11,230 ] ; EUR 33,794 and EUR 34,300 , respectively , where 1 EUR = 11.2015 SEK ) compared with NPH insulin . Sensitivity analysis showed that the principal driver of the benefits associated with insulin detemir was the lower rate of hypoglycemic events ( major and minor events ) vs. NPH insulin , suggesting that detemir might also be cost-saving over a shorter time horizon . Limitations of the analysis include the use of data from a trial outside Sweden in the Swedish setting . Conclusions : Based on clinical input data derived from a previously published r and omized controlled trial , it is likely that in the Swedish setting insulin detemir would be cost-saving in comparison with NPH insulin for the treatment of patients with type 2 diabetes AIMS To determine the cost-effectiveness of adding pioglitazone to existing treatment regimens in patients with Type 2 diabetes with a history of macrovascular disease who are at high risk of further cardiovascular events . METHODS We conducted two analyses . A within-trial cost-effectiveness analysis ( CEA ) based on data from the PROspect i ve pioglitAzone Clinical Trial In macroVascular Events ( PROactive ) Study was performed to estimate the impact of additional pioglitazone treatment on life expectancy , quality -adjusted life expectancy ( QALE ) and macrovascular events . PROactive data was then used as a basis for a lifetime modelling analysis using a modified version of the vali date d CORE diabetes model that simulated the same outcomes over a 35-year time horizon . We accounted for direct medical costs from a health-care payer perspective and related these to the clinical outcomes from the study . Costs and benefits were discounted at 3.5 % per annum and extensive sensitivity analyses were performed to account for uncertainty in input parameters . RESULTS ( i ) Within-trial CEA : compared with placebo , pioglitazone was associated with improved life expectancy ( undiscounted 0.0109 years ) , increased QALE [ 0.0190 quality -adjusted life years ( QALYs ) ] and slightly higher costs ( pounds 102 per patient ) . After a mean treatment period of 3 years , the incremental cost-effectiveness ratio ( ICER ) of pioglitazone vs. placebo was pounds 5396 per QALY gained . The ICERs were relatively insensitive to cost and utility values and were most sensitive to event rates in the pioglitazone arm . ( ii ) Long-term CEA : pioglitazone was associated with improvements in clinical outcomes based on model projections beyond the PROactive Study . Patients treated with pioglitazone could expect improved life expectancy ( undiscounted 0.406 years ) , increased QALE ( 0.152 QALYs ) and higher costs of care ( pounds 619 per patient ) compared with those on existing treatment alone . The base case analysis indicated that the ICER of pioglitazone vs. placebo was pounds 4060 per QALY gained . The cost-effectiveness acceptability curve showed there was an 84.3 % likelihood that pioglitazone would be considered cost-effective in the UK using a willingness-to-pay threshold of pounds 30 000 per QALY gained . These long-term results were most sensitive to variation in the time horizon , the duration of cardiovascular benefit of pioglitazone , and changes in mortality rates . CONCLUSIONS The addition of pioglitazone to existing therapy in patients with Type 2 diabetes at high risk of further cardiovascular events is cost-effective and represents good value for money by currently accepted st and ards in the UK OBJECTIVES To evaluate the cost-effectiveness of pioglitazone versus placebo , given in addition to existing treatment regimens , in patients with type 2 diabetes and evidence of macrovascular disease in Switzerl and . METHODS Event rates corresponding to macrovascular outcomes from the PROactive ( Prospect i ve Pioglitazone Clinical Trial in Macrovascular Events ) trial of pioglitazone were used to project long-term clinical outcomes as part of a modified version of the previously vali date d CORE Diabetes Model . Direct medical costs associated with treatment regimens , complications and patient management were accounted in 2005 values based on Swiss-specific unit costs . Time horizon was set to lifetime ( 35 years ) . Future costs and clinical benefits were discounted at 2.5 % annually in line with Swiss recommendations . One-way sensitivity analyses were performed . RESULTS Addition of pioglitazone was associated with a reduced incidence of most diabetes-related complications , improved life expectancy ( 0.258 years ) and improved quality -adjusted life expectancy ( 0.180 QALYs ) compared with placebo . Pioglitazone treatment increased direct costs by CHF 10,914 per patient over a lifetime horizon . The incremental cost-effectiveness ratio ( ICER ) of pioglitazone versus placebo was CHF 42,274 per life-year gained and CHF 60,596 per QALY gained . ICERs were sensitive to variation in time horizon and duration of pioglitazone treatment effects . With a willingness to pay of CHF 80,000 per QALY in the Swiss setting , there was a 62.5 % chance that pioglitazone would be cost-effective . CONCLUSIONS Addition of pioglitazone to existing therapy was projected to reduce the long-term cumulative incidence of most diabetes complications and improve quality -adjusted life expectancy . Evaluation of incremental direct medical costs associated with these clinical benefits indicated that pioglitazone is likely to be a cost-effective treatment option in the Swiss setting over patient lifetimes Background and Objective Many patients with type 2 diabetes mellitus ( T2DM ) on insulin therapy have inadequate glycaemic control . In such cases , Dutch guidelines recommend unlimited up-titration of insulin , yet in practice many patients never reach their glycaemic target . Clinical evidence shows that dapagliflozin — a highly selective sodium – glucose cotransporter 2 inhibitor — meets a need for these patients , i.e. by reducing glycated haemoglobin levels and bodyweight . We estimated the cost effectiveness and cost utility of adding dapagliflozin to insulin compared with not adding dapagliflozin in patients with T2DM who have inadequate glycaemic control while on insulin . Methods The cost effectiveness of dapagliflozin was estimated using the Cardiff Diabetes Model , using direct comparative efficacy data from a r and omized placebo-controlled trial ( Clinical Trials.gov identifier NCT00673231 ) . In this trial , up-titration of insulin was allowed in case of severe glycaemic imbalance . Risk factor progression and the occurrence of future vascular events were estimated using the United Kingdom Prospect i ve Diabetes Study 68 risk equations . Costs and utilities were derived from the literature . The analysis was conducted from the societal perspective , simulating the remaining lifetime of the patients . Results The overall incidence of macro- and microvascular complications was lower , and life expectancy was greater ( 19.43 versus 19.35 life-years [ LYs ] ) in patients receiving dapagliflozin than in those not receiving dapagliflozin . Patients in the dapagliflozin arm obtained an incremental benefit of 0.42 quality -adjusted life-years ( QALYs ) . The lifetime incremental cost per patient in the dapagliflozin arm was € 2,293 , result ing in an incremental cost-effectiveness ratio of € 27,779 per LY gained and an incremental cost – utility ratio of € 5,502 per QALY gained . Sensitivity and scenario analyses showed that the results were insensitive to variations in modelling assumptions and input variables . Conclusion Dapagliflozin in combination with insulin was estimated to be a cost-effective treatment option for patients with T2DM whose insulin treatment regimen does not provide adequate glycaemic control in a Dutch healthcare setting Background There are few studies investigating the economic value of the Australian practice nurse workforce on the management of chronic conditions . This is particularly important in Australia , where the government needs evidence to inform decisions on whether to maintain or redirect current financial incentives that encourage practice s to recruit practice nurses . Objective The objective of this study was to estimate the lifetime costs and quality -adjusted life-years ( QALYs ) associated with two models of practice nurse involvement in clinical -based activities ( high and low level ) in the management of type 2 diabetes within the primary care setting . Methods A previously vali date d state transition model ( the United Kingdom Prospect i ve Diabetes Study Outcomes Model ) was adapted , which uses baseline prognostic factors ( e.g. gender , haemoglobin A1c [ HbA1c ] ) to predict the risk of occurrence of diabetes-related complications ( e.g. stroke ) . The model was populated by data from Australian and UK observational studies . Costs and utility values associated with complications were summed over patients ’ lifetimes to estimate costs and QALY gains from the perspective of the health care system . All costs were expressed in 2011 Australian dollars ( AU$ ) . The base-case analysis assumed a 40-year time horizon with an annual discount rate of 5 % . Results Relative to low-level involvement of practice nurses in the provision of clinical -based activities , the high-level model was associated with lower mean lifetime costs of management of complications ( −AU$8,738 ; 95 % confidence interval [ CI ] −AU$12,522 to −AU$4,954 ) , and a greater average gain in QALYs ( 0.3 ; 95 % CI 0.2–0.4 ) . A range of sensitivity analyses were performed , in which the high-level model was dominant in all cases . Conclusion Our results suggest that the high-level model is a dominant management strategy over the low-level model in all modelled scenarios . These findings indicate the need for effective primary care-based incentives to encourage general practice s not only to employ practice nurses , but to better integrate them into the provision of clinical services Abstract Objective : To compare the cost-utility of exenatide once weekly ( EQW ) and insulin glargine in patients with type 2 diabetes in the United Kingdom ( UK ) . Research design and methods : The IMS CORE Diabetes Model was used to project clinical and economic outcomes for patients with type 2 diabetes treated with EQW or insulin glargine . Treatment effects and patient baseline characteristics ( mean age : 58 years , mean glycohaemoglobin : 8.3 % ) were taken from the DURATION -3 study . Unit costs and health state utility values were derived from published sources . As the price of EQW is not yet known , the prices of two currently available glucagon-like peptide-1 products were used as benchmarks . To reflect diabetes progression , patients started on EQW switched to insulin glargine after 5 years . The analysis was conducted from the perspective of the UK National Health Service over a time horizon of 50 years with costs and outcomes discounted at 3.5 % . Sensitivity analyses explored the impact of changes in input data and assumptions and investigated the cost utility of EQW in specific body mass index ( BMI ) subgroups . Main outcome measures : Incremental cost-effectiveness ratio ( ICER ) for EQW compared with insulin glargine . Results : At a price equivalent to liraglutide 1.2 mg , EQW was more effective and more costly than insulin glargine , with a base case ICER of £ 10,597 per quality -adjusted life-year ( QALY ) gained . EQW was associated with an increased time to development of any diabetes-related complication of 0.21 years , compared with insulin glargine . Three BMI subgroups investigated ( < 30 , 30–35 and > 35 kg/m2 ) reported ICERs for EQW compared with insulin glargine ranging from £ 9425 to £ 12,956 per QALY gained . Conclusions : At the prices investigated , the cost per QALY gained for EQW when compared with insulin glargine in type 2 diabetes in the UK setting , was within the range normally considered cost effective by NICE . Cost effectiveness in practice will depend on the final price of EQW and the extent to which benefits observed in short-term r and omised trials are replicated in long-term use |
2,215 | 19,588,430 | The evidence does not support the use of topical rubefacients containing salicylates for acute injuries , and suggests that in chronic conditions their efficacy compares poorly with topical non-steroidal antiinflammatory drugs ( NSAIDs ) .
Topical salicylates seem to be relatively well tolerated in the short-term , based on limited data .
There is no evidence at all for topical rubefacients with other components | BACKGROUND Rubefacients ( containing salicylates or nicotinamides ) cause irritation of the skin , and are believed to relieve various musculoskeletal pains .
They are available on prescription , and are common components in over-the-counter remedies .
A non-Cochrane review in 2004 found limited evidence for efficacy .
OBJECTIVES To review current evidence for efficacy and safety of topically applied rubefacients in acute and chronic painful musculoskeletal conditions in adults . | OBJECTIVE To assess the efficacy and safety of a copper-salicylate gel in osteoarthritis of the hip and knee . DESIGN R and omised , double-blind , placebo-controlled study . SETTING Rheumatology Clinic of St Vincent 's Hospital , Sydney , New South Wales ( a tertiary referral hospital ) , June 1993 to October 1994 . PATIENTS 116 patients with pain associated with osteoarthritis of the hip and /or knee ( diagnosed by criteria of the European League against Rheumatism ) , drawn from patients attending the Clinic or self-referred after newspaper advertisements . INTERVENTION Copper-salicylate or placebo gel ( 1.5 g ) applied twice daily to the forearm for four weeks . OUTCOME MEASURES Self- assessment of pain before the trial and after two and four weeks of treatment ; patient and investigator assessment s of efficacy ; additional analgesia required ; adverse reactions ; and withdrawal rates . RESULTS Pain scores at rest and on movement decreased in both the copper-salicylate and placebo groups by 13%-20 % . There was no significant difference between the two groups for decrease in pain score , patient and investigator efficacy ratings , number of patients requiring paracetamol for extra analgesia ( active , 77 % ; placebo , 71 % ) and average dose of paracetamol ( active , 555 mg/day ; placebo , 600 mg/day ) . Significantly more patients in the copper-salicylate group reported adverse reactions ( 83 % versus 52 % of the placebo group ) , most commonly skin reactions , and withdrew from the trial because of these reactions ( 17 % versus 1.7 % of the placebo group ) . CONCLUSION Copper-salicylate gel applied to the forearm was no better than placebo gel as pain relief for patients with osteoarthritis of the hip or knee , but produced significantly more skin rashes Objective : To determine the clinical effects of the treatment of lumbar disc herniation with herbal magnetic corsets . Design : A r and omized control trial . Setting : The outpatient and inpatient departments of the Rehabilitation Center of the West China Hospital . Patients : Sixty patients with clinical ly diagnosed lumbar disc herniation were included in the study . Interventions : Both groups received lumbar traction , medium frequency electrotherapy and massage , whereas the experimental group wore herbal magnetic corsets in addition . Main outcome measures : Pain and lumbar function were assessed before treatment and at one week , two weeks and four weeks after intervention . Results : Both groups reported improvements in pain and lumbar function after treatment ( P 0.05 or P 0.001 ) . However , the experimental group reported gradually increasing relief over time leading to a better curative effect than observed in the control group ( P 0.05 for visual analogue scale or P 0.001 for lumbar function ) . Conclusion : Herbal magnetic corsets can facilitate the reduction of pain caused by lumbar disc herniation and can improve lumbar function . This is a safe and effective non-operative therapeutic option for treatment of lumbar disc herniation 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 Enelbin-Rheuma-ointment and a reference ointment were compared with regard to effectiveness in a double-blind trial in 100 patients with gonarthrosis , osteoarthrosis of the spine and humeroscapular periarthropathy . Both ointments showed good results regarding spontaneous pain , pain on pressure and motion , reduction of mobility , swelling and muscular tension . The success of treatment was statistically significantly better in the Enelbin-Rheuma-ointment treated patients Abstract This r and omized , double-blind study was design ed to evaluate the effectiveness of the topical cream Theraflex-TMJ ( NaBob/Rx , San Mateo , CA ) in patients with masseter muscle pain and temporom and ibular joint ( TMJ ) pain . Fifty-two subjects ( 5 males and 47 females ) were instructed to apply a cream over the afflicted masseter muscle(s ) or over the jaw joint(s ) twice daily for two weeks . Theraflex-TMJ cream was used by the experimental group , while a placebo cream was used by the control group . The means of pain ratings were calculated prior to the application of the cream ( baseline ) , after ten days of tx ( period 1 ) , and 15 days of tx ( period 2 ) days of treatment and five days after stopping the treatment ( follow-up ) . There was a significant decrease in reported pain levels from baseline in the experimental group for period 1 ( p<0.01 ) , period 2 ( p<0.001 ) , and follow-up ( p<0.01 ) . For the control group , no significant differences were found between the different time periods ( p>0.05 ) . There was evidence of minor side effects such as skin irritation and /or burning on the site of the application in two subjects in the experimental as well as two subjects in the control groups . The data strongly suggest that Theraflex-TMJ topical cream is safe and effective for reducing pain in the masseter muscle and the temporom and ibular joint Twenty-five patients with symptomatic osteoarthritis ( OA ) of the knee were treated topically for one week with either 10 % trolamine salicylate cream or placebo cream in a r and omized double-blind crossover study . No significant difference was found in subjective or objective measures of pain relief between the treatment and control groups . Eight patients preferred " active " test cream , six preferred placebo , and 11 had no preference . No side effects were reported . Topically applied 10 % trolamine salicylate cream did not relieve the pain of OA of the knee any more than did placebo Forty patients with acute mechanical low-back pain were treated in a double-blind manner with either Rado-Salil ® or placebo for 14 days . Statistically significant improvements in spontaneous pain , muscular contracture and in both the patient 's and physician 's opinions occurred by day 3 . These improvements persisted at day 14 and , in addition , there were statistically significant improvements in the finger – floor distance and the degree of lumbar extension . Treatment with Rado-Salil ® also allowed significant reduction in the use of oral analgesics . Only a few localized transient side-effects , requiring no specific treatment , were observed This study was design ed to evaluate the effectiveness in relief of pain and rigidity of a 10|X% trolamine salicylate cream compared with a placebo cream identical in smell and appearance , for subjects with osteoarthritis in their h and s. This was a one-application , r and omized , double-blind , placebo-controlled , parallel study conducted in 81 patients . Pain and stiffness were assessed in the morning upon subjects ' awakening ( baseline ) and at 30 , 45 , and 120 min after a 4-min rubbing application . Analgesic response was determined using the sum of pain intensity differences ( SPID ) and the sum of stiffness intensity differences ( SSID ) ; the sum across the observation points derived from a pain/stiffness rating scale . Trolamine salicylate was significantly superior to the placebo in improving SPID ( p = 0.0492 ) and in improving SSID scores for both h and s ( p = 0.0283 ) . Treatment differences in absolute pain and stiffness scores were significant ( p |Ml 0.05 ) at 45 min after application . A 10|X% trolamine salicylate cream was shown to be safe and effective for the temporary relief of minor pain and stiffness associated with osteoarthritis in the h and s. This formulation has no smell or counter-irritating properties ; patient acceptability was good In a r and omised , placebo-controlled , double-blind study with parallel group comparison , the efficacy and tolerability of topical treatment with a mucopolysaccharide polysulphate/salicylic acid cream was investigated in 156 patients with acute sprains of the knee or ankle joint . There was a more rapid reduction in pain on movement ( the main parameter ) in the active drug group compared with the placebo group . On day 9 after r and omisation the difference was highly significant . There were no adverse events in the active drug group & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed Acute low back pain is a very common condition in Western industrialised countries . In most cases analgesics or topical medications are prescribed at first encounter with the general practitioner ( GP ) . The aim of this study was to investigate whether the homeopathic gel Spiroflor SRL gel ( SRL ) is equally effective and better tolerated than Cremor Capsici Compositus FNA ( CCC ) in patients with acute low back pain . A multi-centre , r and omised , double-blind , controlled clinical trial was conducted in the practice s of 19 GPs in the districts of Bristol and Manchester , UK . One hundred and sixty-one subjects suffering from acute low back pain were treated for one week either with SRL or with CCC . Pain was scored on a 100 mm visual analogue scale ( VAS ) . Main efficacy parameter VAS reduction was compared between treatments . Evaluation of safety was primarily based on the number of subjects with adverse events ( AEs ) , withdrawals due to an AE and adverse drug reactions ( ADRs ) . The mean difference between the VAS reduction in the SRL group and the CCC group adjusted for VAS at baseline and age was -0.6 mm ( 90 % CI = -6.5 - 5.3 mm ) . Fewer subjects in the SRL group ( 11 % ) experienced an AE than in the CCC group ( 26 % ) . The same applies to the number of subjects with an ADR ( 3/81 = 4 % vs 18/74 = 24 % ) and the number of subjects withdrawn due to an ADR ( 0/81 = 0 % vs 8/74 = 11 % ) . In conclusion , SRL and CCC are equally effective in the treatment of acute low back pain , however , SRL has a better safety profile . Spiroflor SRL gel is preferable to Capsicum-based products for the topical treatment of low back pain , because of the lower risk of adverse effects 2-(2-Hydroxyethoxy)ethyl-N-(a , a , a-trifluoro-m-tolyl)anthranilate ( etofenamate , Rheumon Gel ) , a percutaneously active antirheumatic containing etofenamate as active principle has been subjected to clinical studies in both hospitalized and out- patients in various types of rheumatic disease . These trials included double-blind studies against placebo gel , controlled comparative studies against two topical commercial products ( ointmentI : combination of 2-hydroxyethyl salicylate and p-menthan-3-ol ; ointment II : 3,5-dioxo-1,2-diphenyl-4-n-butylpyrazolidine ) and open trials for efficacy and tolerance . Of the 760 patients taking part in the trials , 556 were treated with Rheumon Gel Camphor , menthol , and methyl salicylate occur in numerous over-the-counter products . Although extensively used , there have been no estimates of human exposure following administration via dermal application . Furthermore , there is little information about the pharmacokinetics of those compounds . The authors report the plasma concentrations of the intact compounds as a function of dose following dermal patch application . Three groups of 8 subjects ( 4 male , 4 female ) applied a different number of commercial patches ( 2 , 4 , or 8) to the skin for 8 hours . Plasma sample s were assayed using sensitive and selective gas-chromatographic methods . For the 8-patch group , the average maximum plasma concentrations ( Cmax + /- SD ) were 41.0 + /- 5.8 ng/mL , 31.9 + /- 8.8 ng/mL , and 29.5 + /- 10.5 ng/mL for camphor , menthol , and methyl salicylate , respectively . The corresponding values for the 4-patch group were 26.8 + /- 7.2 ng/mL , 19.0 + /- 5.4 ng/mL , and 16.8 + /- 6.8 ng/mL. The harmonic mean terminal half-lives were 5.6 + /- 1.3 hours , 4.7 + /- 1.6 hours , and 3.0 + /- 1.2 hours for camphor , menthol , and methyl salicylate , respectively . The 2-patch group had measurable but low plasma concentrations of each compound . Low-dose dermal application for an extended time results in low plasma concentrations of all 3 compounds . Four and 8 patches , when applied for 8 hours , gave measurable and nearly proportional plasma concentrations . Although unable to determine the absolute dermal bioavailability of these compounds , there appears to be relatively low systemic exposure to these potentially toxic compounds , even when an unrealistically large number of patches are applied for an unusually long time The efficacy of Mobilat ointment ( 100 g contain : Extract . suprarenale 1.0 g , Mucopolysaccharide-polysulfate 0.2 g , salicylic acid 2.0 g ) in the treatment of acute lateral distortions of the ankle was tested in a r and omised , placebo-controlled , double blind study . The criteria used for the assessment of the progress of healing were the pressure distribution during walking , the swelling of the injured region and the evaluation of pain using a visual analogue scale . During the period of treatment and observation lasting 2 weeks , all the assessment criteria showed a more rapid regression in the symptoms and signs of the disorder on treatment with the active product . The differences were statistically significant for all the criteria assessed Two clinical studies were carried out to investigate the efficacy and safety as well as the local and systemic availability of a hydroxyethylsalicyclate gel . A double blind , multicenter trial , involving 113 patients with nonarticular rheumatic back pain , revealed statistically significant relief of pain as compared with placebo . Local and systemic tolerance was excellent . An open study of bioavailability after local application in 16 patients showed a mean salicylate concentration of 0.93 + /- 0.5 microgram/ml in the synovial fluid and 0.40 + /- 0.23 microgram/ml in the synovial membrane , compared with 0.14 + /- 0.04 microgram/ml in the serum . Genetisinic acid was not detected , while OH-hippuric acid was detected only in the serum and synovial fluid |
2,216 | 18,069,023 | Pooled estimates were not influenced by follow-up length .
Conversion and reintervention rates were not significantly lower for small AAA .
EVAR in small versus large AAA might be associated with lower operative mortality , aneurysm-related mortality and aneurysm rupture . | AIM To compare the results of endovascular repair ( EVAR ) in large and small ( diameter < 5.5 cm ) abdominal aortic aneurysms ( AAA ) . | Objective : To assess the outcome of endovascular repair ( EVAR ) of small abdominal aortic aneurysms ( AAA , ≤5.5 mm maximum diameter ) in Australia . Summary Background Data : R and omized trials have suggested that small AAAs should not be treated by open surgery . EVAR is associated with less perioperative mortality than open surgery for large AAAs . We assessed the outcome of EVAR of small AAAs as part of a national audit . Methods : ASERNIP-S carried out a prospect i ve audit of EVAR performed between November 1999 and May 2001 in Australia . A total of 478 of the 961 patients entered underwent treatment of a small AAA . Data were collected regarding preoperative characteristics , procedural outcome , and intermediate success . Median follow-up was 3.2 years . Data were analyzed using Kaplan-Meier and Cox proportional hazard analyses . Results : The 30-day mortality and technical success rates were 1.1 % and 98 % , respectively . Postoperative complications occurred in 29 % . Survival was 84 % and 52 % at 3 and 5 years , respectively . Primary , assisted primary , and secondary clinical success rates were 72 % , 79 % , and 82 % , respectively , at 3 years . Reintervention rate was 11 % at 3 years ; however , 15 % of patients continued to have significant aortic sac enlargement . Survival was reduced in patients considered unfit for general anesthesia ( odds ratio = 2.6 ; 95 % confidence interval , 1.4–4.8 , P = 0.002 ) or those who had elevated preoperative serum creatinine ( odds ratio = 2.0 ; 95 % confidence interval , 1.3–3.0 , P = 0.001 ) . Conclusions : EVAR can be carried with good perioperative outcome in patients with small AAA ; however , intermediate success is hampered by the need for reintervention and continued aortic sac enlargement . At present , widespread treatment of small AAAs by EVAR would appear inappropriate OBJECTIVE The effect of population screening for abdominal aortic aneurysm ( AAA ) disease on morbidity and mortality has been comprehensively studied and reported . However , the effect of early AAA detection on suitability for endovascular aneurysm repair ( EVAR ) remains unknown . Considering the importance of such an effect on future health economics , we sought to assess the possible effect of AAA ultrasound surveillance on suitability for EVAR . METHODS This was a prospect i ve cohort study . From January 2002 to August 2003 , consecutive AAA patients selected for open elective repair were placed into one of two groups according to mode of presentation . The first group included patients referred from a local well-established AAA ultrasound screening and surveillance program ( ultrasound surveillance [ AAA-S ] group ) . The second group included patients referred from neighboring unscreened regions with incidentally diagnosed AAA ( incidental [ AAA-I ] group ) . All patients underwent preoperative computed tomographic angiography . By using three-dimensional reconstruction software , computed tomographic images were assessed by two blinded observers for suitability for EVAR by using the criteria for a modular endovascular device . RESULTS Of 74 patients included in the study , 41 were in the AAA-S group , and 31 were in the AAA-I group . The median aneurysm diameter was 72.3 mm ( range , 50.7 - 83.7 mm ) for AAA-I and 65 mm ( range , 50.7 - 79.2 mm ) for AAA-S ( P < .47 ) . Suitability for EVAR was 41 % in the AAA-S group and 45 % in the AAA-I group ( P < .47 ) . CONCLUSIONS Early detection and surveillance of AAA does not seem to increase suitability for EVAR . Suitability for EVAR seems to be determined early on in an aneurysm 's life . On the basis of current device technology , referral for intervention from an AAA surveillance program may need to be initiated at a size well below 5.5 cm if an increase in EVAR suitability is to be expected HYPOTHESIS Small infrarenal abdominal aortic aneurysms have a more favorable clinical and morphologic outcome compared with medium and large abdominal aortic aneurysms following endovascular aneurysm repair(EVAR ) . DESIGN A prospect i ve clinical series of 206 patients undergoing elective EVAR between 1996 and 2001 . SETTING A tertiary care academic health center . PATIENTS Patients were grouped according to aneurysm size : small ( < 50 mm ) , medium ( 50 - 60 mm ) , and large ( > 60 mm ) . INTERVENTIONS Primary EVAR and secondary procedures to secure fixation of the stent graft and surgical conversions . MAIN OUTCOME MEASURES Aneurysm diameter , endoleaks , and long-term morphologic changes were analyzed postoperatively with 3-dimensional reconstructions of computed tomographic angiograms . RESULTS Groups were similar in age , comorbidities , and follow-up ( mean + /- SD , 32.1 + /- 11.8 months ) . There were 30 small aneurysms , 92 medium aneurysms , and 84 large aneurysms , with a mean size of 45.1 + /- 3.7 mm , 53.8 + /- 3.1 mm , and 66.1 + /- 6.8 mm , respectively ( P<.01 ) . There was no significant difference in proximal neck or iliac artery diameter among the 3 groups . The proximal aortic neck length ( 28.1 + /- 11.6 mm [ small ] ; 23.9 + /- 11.3 mm [ medium ] ; and 22.1 + /- 11.6 mm [ large ] ; P<.05 ) was significantly shorter in large aneurysms . Furthermore , there was a significant increase ( 6 % [ small ] ; 15 % [ medium ] ; and 21 % [ large ] ; P<.05 ) in angulated necks in large aneurysms . Following treatment , aneurysm diameter remained stable in most patients ( 83 % [ small ] ; 82 % [ medium ] ; and 83 % [ large ] ) , with a mean decrease of 2.0 + /- 6.5 mm , 2.1 + /- 6.1 mm , and 3.7 + /- 7.7 mm in each group , respectively ( P = .45 ) . There was no difference in the incidence of endoleaks , aneurysm contraction , or aneurysm expansion based on preoperative aneurysm diameter . Secondary procedures were performed in 5 ( 20 % ) of 25 , 9 ( 5.2 % ) of 170 , and 5 ( 36 % ) of 11 aneurysms that contracted , remained stable , or exp and ed , respectively , following EVAR ( P<.05 ) . CONCLUSIONS There is a 15 % increase in neck angulation and a 27 % decrease in neck length in large compared with small infrarenal abdominal aortic aneurysms , with no difference in outcome . Aneurysms that are stable following EVAR have a significantly lower incidence of requiring secondary procedures OBJECTIVE To compare the outcome of patients with small abdominal aortic aneurysms ( AAA ) treated in a prospect i ve trial of endovascular aneurysm repair ( EVAR ) to patients r and omized to the surveillance arm of the UK Small Aneurysm Trial . METHOD All patients with small AAA ( < or = 5.5 cm diameter ) treated with a stent graft ( EVARsmall ) in the multicenter AneuRx clinical trial from 1997 to 1999 were review ed with follow up through 2003 . A subgroup of patients ( EVARmatch ) who met the age ( 60 - 76 years ) and aneurysm size ( 4.0 - 5.5 cm diameter ) inclusion criteria of the UK Small Aneurysm Trial were compared to the published results of the surveillance patient cohort ( UKsurveil ) of the UK Small Aneurysm Trial ( NEJM 346:1445 , 2002 ) . Endpoints of comparison were aneurysm rupture , fatal aneurysm rupture , operative mortality , aneurysm related death and overall mortality . The total patient years of follow-up for EVAR patients was 1369 years and for UK patients was 3048 years . Statistical comparisons of EVARmatch and UKsurveil patients were made for rates per 100 patient years of follow up ( /100 years ) to adjust for differences in follow-up time . RESULTS The EVARsmall group of 478 patients comprised 40 % of the total number of patients treated during the course of the AneuRx clinical trial . The EVARmatch group of 312 patients excluded 151 patients for age < 60 or > 76 years and 15 patients for AAA diameter < 4 cm . With the exception of age , there were no significant differences between EVARsmall and EVARmatch in pre-operative factors or post-operative outcomes . In comparison to the UKsurveil group of 527 patients , the EVARmatch group was slightly older ( 70 + /- 4 vs. 69 + /- 4 years , p = 0.009 ) , had larger aneurysms ( 5.0 + /- 0.3 vs. 4.6 + /- 0.4 cm , p < 0.001 ) , fewer women ( 7 vs. 18 % , p < 0.001 ) , and had a higher prevalence of diabetes and hypertension and a lower prevalence of smoking at baseline . Ruptures occurred in 1.6 % of EVARmatch patients and 5.1 % of UKsurveil patients ; this difference was not significant when adjusted for the difference in length of follow up . Fatal aneurysm rupture rate , adjusted for follow up time , was four times higher in UKsurveil ( 0.8/100 patient years ) than in EVARmatch ( 0.2/100 patient years , p < 0.001 ) ; this difference remained significant when adjusted for difference in gender mix . Elective operative mortality rate was significantly lower in EVARmatch ( 1.9 % ) than in UKsurveil ( 5.9 % , p < 0.01 ) . Aneurysm-related death rate was two times higher in UKsurveil ( 1.6/100 patient years ) than in EVARmatch ( 0.8/100 patient years , p = 0.03 ) . All-cause mortality rate was significantly higher in UKsurveil ( 8.3/100 patient years ) than in EVARmatch ( 6.4/100 patient years , p = 0.02 ) . CONCLUSIONS It appears that endovascular repair of small abdominal aortic aneurysms ( 4.0 - 5.5 cm ) significantly reduces the risk of fatal aneurysm rupture and aneurysm-related death and improves overall patient survival compared to an ultrasound surveillance strategy with selective open surgical repair OBJECTIVE To study the growth rate and factors influencing progression of small infrarenal abdominal aortic aneurysms ( AAA ) . DESIGN Observational , longitudinal , prospect i ve study . PATIENTS AND METHODS We followed patients with AAA < 5 cm in diameter in two groups . Group I ( AAA 3 - 3.9 cm , n = 246 ) underwent annual ultrasound scans . Group II ( AAA 4 - 4.9 cm , n = 106 ) underwent 6-monthly CT scans . RESULTS We included 352 patients ( 333 men and 19 women ) followed for a mean of 55.2+/-37.4 months ( 6.3 - 199.8 ) . The mean growth rate was significantly greater in group II ( 4.72+/-5.93 vs. 2.07+/-3.23 mm/year ; p<0.0001 ) . Group II had a greater percentage of patients with rapid aneurysm expansion ( > 4 mm/year ) ( 36.8 vs. 13.8 % ; p<0.0001 ) . The classical cardiovascular risk factors did not influence the AAA growth rate in group I. Chronic limb ischemia was associated with slower expansion ( < or = 4 mm/year ) ( OR 0.47 ; CI 95 % 0.22 - 0.99 ; p = 0.045 ) . Diabetic patients in group II had a significantly smaller mean AAA growth rate than non-diabetics ( 1.69+/-3.51 vs. 5.22+/-6.11 mm/year ; p = 0.032 ) . CONCLUSIONS The expansion rate of small AAA increases with the AAA size . AAA with a diameter of 3 - 3.9 cm exp and slowly , and they are very unlikely to require surgical repair in 5 years . Many 4 - 4.9 cm AAA can be expected to reach a surgical size in the first 2 years of follow-up . Chronic limb ischemia and diabetes are associated with reduced aneurysm growth rates BACKGROUND Although the initial results of endovascular repair of abdominal aortic aneurysms were promising , current evidence from controlled studies does not convincingly show a reduction in 30-day mortality relative to that achieved with open repair . METHODS We conducted a multicenter , r and omized trial comparing open repair with endovascular repair in 345 patients who had received a diagnosis of abdominal aortic aneurysm of at least 5 cm in diameter and who were considered suitable c and i date s for both techniques . The outcome events analyzed were operative ( 30-day ) mortality and two composite end points of operative mortality and severe complications and operative mortality and moderate or severe complications . RESULTS The operative mortality rate was 4.6 percent in the open-repair group ( 8 of 174 patients ; 95 percent confidence interval , 2.0 to 8.9 percent ) and 1.2 percent in the endovascular-repair group ( 2 of 171 patients ; 95 percent confidence interval , 0.1 to 4.2 percent ) , result ing in a risk ratio of 3.9 ( 95 percent confidence interval , 0.9 to 32.9 ) . The combined rate of operative mortality and severe complications was 9.8 percent in the open-repair group ( 17 of 174 patients ; 95 percent confidence interval , 5.8 to 15.2 percent ) and 4.7 percent in the endovascular-repair group ( 8 of 171 patients ; 95 percent confidence interval , 2.0 to 9.0 percent ) , result ing in a risk ratio of 2.1 ( 95 percent confidence interval , 0.9 to 5.4 ) . CONCLUSIONS On the basis of the overall results of this trial , endovascular repair is preferable to open repair in patients who have an abdominal aortic aneurysm that is at least 5 cm in diameter . Long-term follow-up is needed to determine whether this advantage is sustained 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 OBJECTIVE Australian cases of endovascular aneurysm repair ( EVAR ) performed between 1999 and 2001 have been evaluated to determine the mid-term ( 6 months to 5 years ) safety and efficacy of the procedure . This study looks at predictors of success , based on mid-term follow-up data . DESIGN OF STUDY This study uses results obtained from a prospect i ve semi-voluntary register ( audit ) of Australian data obtained from surgeons in the private and public sector . RESULTS Peri-operative mortality for patients enrolled in the audit was 1.8 % . Ninety-three percent of procedures were technically successful ( 890/961 ) . Nearly 13 % of patients have had re- interventions ( mostly endoluminal ) at follow-up . Analysis of audit data shows that the likelihood of experiencing post-operative complications or requiring additional procedures increases with ASA rating , increasing age , large pre-operative aneurysm size , aneurysm angle > 45 degrees and number of co-morbid conditions diagnosed . CONCLUSIONS This study confirms satisfactory mid-term results in a , national rather than unit specific , setting . Predictors of clinical failure or need for re-intervention include large aneurysm size , neck angulation > or=45 degrees and short infrarenal neck OBJECTIVE The CAESAR Trial aims to assess the outcome of endovascular repair ( EVAR ) vs surveillance of small abdominal aortic aneurysms ( AAA ) with maximum diameter of 4.1 - 5.4 cm on computerised tomography ( CT ) scan . DESIGN Patients between 50 and 80 years of age , with small AAA , anatomically suitable for EVAR , are r and omly allocated to early EVAR or surveillance . The primary outcome measure is survival . Secondary endpoints include : aneurysm-related deaths ( defined as any death caused directly or indirectly by rupture or endovascular/open aneurysm repair ) , AAA rupture , peri-operative or late complications , conversion to open repair , complications associated with delayed treatment including loss of treatment options , AAA growth rates and quality of life . Target recruitment is 740 patients to show that early EVAR is associated with a 15 % survival benefit at 54 months . PROGRESS R and omization started in September 2004 . By the end of April 2005 , 86 patients had been enrolled by 10 active European centres . Completion of recruitment is expected for September 2006 and publication of the results in mid 2007 OBJECTIVE The appropriate size threshold for endovascular repair of small abdominal aortic aneurysms ( AAA ) is unclear . We studied the outcome of endovascular aneurysm repair ( EVAR ) as a function of preoperative aneurysm diameter to determine the relationship between aneurysm size and long-term outcome of endovascular repair . METHODS We review ed the results of 923 patients treated in a prospect i ve , multicenter clinical trial of EVAR . Small aneurysms were defined according to two size thresholds of 5.5 cm and 5.0 cm . Two-way analysis was used to compare patients with small aneurysms ( < 5.5 cm , n = 441 ) to patients with large aneurysms ( > or = 5.5 cm , n = 482 ) . An ordered three-way analysis was used to compare patients with small AAA ( < 5.0 cm , n = 145 ) , medium AAA ( 5.0 to 5.9 cm , n = 461 ) , and large AAA ( > or = 6.0 cm , n = 317 ) . The primary outcome measures of rupture , AAA-related death , surgical conversion , secondary intervention , and survival were compared using Kaplan-Meier estimates at 5 years . RESULTS Median aneurysm size was 5.5 cm . The two-way comparison showed that 5 years after EVAR , patients with small aneurysms ( < 5.5 cm ) had a lower AAA-related death rate ( 1 % vs 6 % , P = .006 ) , a higher survival rate ( 69 % vs 57 % , P = .0002 ) , and a lower secondary intervention rate ( 25 % vs 32 % , P = .03 ) than patients with large aneurysms ( > or = 5.5 cm ) . Three-way analysis revealed that patients with small AAAs ( < 5.0 cm ) were younger ( P < .0001 ) and were more likely to have a family history of aneurysm ( P < .05 ) , prior coronary intervention ( P = .003 ) , and peripheral occlusive disease ( P = .008 ) than patients with larger AAAs . Patients with smaller AAAs also had more favorable aortic neck anatomy ( P < .004 ) . Patients with large AAAs were older ( P < .0001 ) , had higher operative risk ( P = .01 ) , and were more likely to have chronic obstructive pulmonary disease ( P = .005 ) , obesity ( P = .03 ) , and congestive heart failure ( P = .004 ) . At 5 years , patients with small AAAs had better outcomes , with 100 % freedom from rupture vs 97 % for medium AAAs and 93 % for large AAAs ( P = .02 ) , 99 % freedom from AAA-related death vs 97 % for medium AAAs and 92 % for large AAAs ( P = .02 ) and 98 % freedom from conversion vs 92 % for medium AAAs and 89 % for large AAAs ( P = .01 ) . Survival was significantly improved in small ( 69 % ) and medium AAAs ( 68 % ) compared to large AAAs ( 51 % , P < .0001 ) . Multivariate Cox proportional hazards modeling revealed that aneurysm size was a significant independent predictor of rupture ( P = .04 ; hazard ratio [ HR ] , 2.195 ) , AAA-related death ( P = .03 ; HR , 2.007 ) , surgical conversion ( P = .007 ; HR , 1.827 ) , and survival ( P = .001 ; HR , 1.351 ) . There were no significant differences in secondary intervention , endoleak , or migration rates between small , medium , and large AAAs . CONCLUSIONS Preoperative aneurysm size is an important determinant of long-term outcome following endovascular repair . Patients with small AAAs ( < 5.0 cm ) are more favorable c and i date s for EVAR and have the best long-term outcomes , with 99 % freedom from AAA death at 5 years . Patients with large AAAs ( > or = 6.0 cm ) have shorter life expectancy and have a higher risk of rupture , surgical conversion , and aneurysm-related death following EVAR compared to patients with smaller aneurysms . Nonetheless , 92 % of patients with large AAAs are protected from AAA-related death at 5 years . Patients with AAAs of intermediate size ( 5 to 6 cm ) represent most of the patients treated with EVAR and have a 97 % freedom from AAA-related death at 5 years Endovascular aneurysm repair ( EVAR ) has become an established alternative to open repair ( OR ) . We present a consecutive series of 486 elective patients with large infra-renal aortic abdominal aneurysm , comparing OR with EVAR . Prospect i ve data collected during an 8-year period from January 1997 to October 2005 was review ed . Statistical analysis performed using SPSS data editor with chi(2 ) tests and Mann-Whitney U-tests . There were 486 patients with 329 OR ( 293 males , 36 females ) with median age of 72 years with median diameter 6.3 cm and 157 EVAR ( 148 males , 9 females ) with median age 75 years with median diameter 6.1 cm . Mortality was 13 ( 4 % ) for OR and 5 ( 3.2 % ) for EVAR ( three of whom were in the UK EVAR 2 trial ) . Blood loss was significantly less for EVAR 500 ml vs. 1500 ml for OR . Sixty-five ( 19.8 % ) patients with OR had significantly more peri-operative complications compared with 14 ( 8.9 % ) with EVAR . The length of stay in hospital was significantly less for EVAR . This non-r and omised study shows that although EVAR does not have a statistically significantly lower mortality , it does have statistically significantly lower complication rates compared with OR . EVAR can be achieved with good primary success , but long-term follow-up is essential to assess durability PURPOSE The aim of this study was to seek a relationship between the morphologic features of abdominal aortic aneurysms and the feasibility of endoaortic grafting . METHODS Between June 1995 and January 1996 , 86 patients were prospect ively studied with contrast-enhanced spiral computed tomographic scans , which provided 35 parameters concerning the aorta and iliac arteries . Four groups were established according to the diameter of abdominal aortic aneurysms : group A , 40 to 49 mm , 36 patients ; group B , 50 to 59 mm , 26 patients ; group C , 60 to 69 mm , 10 patients ; and group D , greater than 70 mm , 14 patients . RESULTS There was a correlation between the diameter and length of the aneurysm ( p < 0.0001 ) and between aneurysm diameter and length of the proximal neck ( p < 0.001 ) . Presence of a proximal neck or a distal neck was more frequent in groups A and B than in groups C and D ( p < 0.01 ) . The feasibility of endovascular grafting was estimated at between 50 % and 61.6 % and was higher in groups A and B than in groups C and D ( p < 0.01 ) . CONCLUSIONS This study has shown an inverse relationship between the diameter of the aneurysm and the length of the aortic neck ( correlation coefficient , -0.3640 , p < 0.001 ) . The diameter of an aneurysm was the most useful of the 31 parameters measured in predicting the feasibility of endoaortic grafting , estimated at 71 % for aneurysms less than 60 mm in diameter and 37.5 % for aneurysms greater than 60 mm in diameter ( p < 0.01 ) OBJECTIVES Endovascular stent grafting offers a potentially less invasive option for treatment of abdominal aortic aneurysm . Clinical benefit has been demonstrated with respect to early parameters such as blood transfusion , return of gastrointestinal function , and length of hospital stay . Endovascular repair , however , has been criticized on the basis of inferior long-term outcome . Secondary procedures may be necessary to address durability issues such as migration , high-pressure endoleak , graft limb thrombosis , and degeneration of the stent-fabric structure itself , issues that may compromise the primary goal of aneurysm repair , protection from rupture . METHODS Between 1996 and 2002 , 703 patients underwent endovascular treatment of infrarenal abdominal aortic aneurysm at The Clevel and Clinic Foundation . During this time , five devices were used : Ancure , AneuRx , Excluder , Talent , and Zenith . Outcome was assessed with physical examination , lower extremity arterial studies , plain abdominal radiography , and computed tomography at discharge , at 1 , 6 , and 12 months postoperatively , and annually thereafter . Secondary procedures were defined as any procedure , exclusive of diagnostic angiography , performed after stent graft implantation , directed at treatment of aneurysm-related events . Multivariable statistical techniques for censored data ( Cox proportional hazards modeling ) were used to determine baseline parameters associated with need for secondary procedures over follow-up , with calculation of hazards ratio ( HR ) and 95 % confidence interval ( CI ) . RESULTS Patient follow-up averaged 12.2 + /- 11.7 months . Patient survival was 90 % + /- 1.4 % at 1 year , 78 % + /- 2.6 % at 2 years , and 70 % + /- 3.8 % at 3 years . Aneurysm rupture occurred in 3 patients ( 0.4 % ) , accounting for rupture risk of 1.4 % over the first 2 years of follow-up ( Kaplan-Meier method ) . Overall , 128 secondary procedures were required in 104 patients ( 15 % ) , with a cumulative risk of 12 % + /- 1.5 % at 1 year , 24 % + /- 2.8 % at 2 years , and 35 % + /- 4.4 % at 3 years after stent graft implantation . Among the secondary procedures , new stent grafts and extensions were placed in 34 patients ( 27 % ) , embolization of endoleak was performed in 33 patients ( 26 % ) , and open surgical conversion was undertaken in 11 patients ( 9 % ) . Periprocedural mortality of secondary procedures was 8 % overall , but was 18 % for patients undergoing open surgical conversion . Multivariable modeling identified the date the procedure was performed ( HR , 1.53 per 3-month period of study ; CI , 1.22 - 1.92 ; P < .001 ) and aneurysm size ( HR , 1.35 per centimeter of minor axis ; CI , 1.13 - 1.60 ; P < .001 ) as independent predictors of need for secondary procedures . CONCLUSIONS Current endovascular devices are associated with a relatively high rate of complications over mid-term follow-up , culminating in frequent need for secondary remedial procedures . With strict follow-up imaging compliance , however , risk for rupture and aneurysm-related death remain exceedingly low . Newer technology may achieve improved durability and a lower requirement for secondary procedures , while maintaining the minimally invasive nature of presently available devices OBJECTIVE Several studies have suggested that proximal aortic neck dilatation ( AND ) is a frequent event after balloon-exp and able endografting . Yet few data are available on AND after repair with self-exp and able stent grafts . To investigate incidence , predictive factors , and clinical consequences of AND , computed tomography ( CT ) scans obtained at intervals during follow-up of 230 patients who had undergone endoluminal abdominal aortic aneurysm ( AAA ) repair with self-exp and able stents were review ed . SUBJECTS Between April 1997 and March 2001 , 318 patients underwent endoluminal AAA repair with a self-exp and able endograft at our unit . CT scans obtained at 1 and 12 months after surgery and yearly thereafter were prospect ively stored in a computer imaging data base . Two hundred thirty patients were available for minimum 1-year assessment . Two vascular surgeons with tested interobserver agreement review ed 686 CT scans . Diameter of the proximal aortic neck was measured as the minor axis of the first CT section that contained at least half of the proximal portion of the endograft . For endografts with suprarenal attachment the first scan below the lowest renal artery was considered . Diameter change of 3 mm or more between the CT scan at 1 month and subsequent evaluations was defined as AND . Nine possible independent predictors of AND were analyzed with Cox regression analysis . RESULTS Median follow-up was 24 months ( range , 12 - 54 months ) . In 2 patients , AAA ruptured during follow-up . CT scans for 65 patients ( 28 % ) showed AND . Thirteen patients with AND ( 5.6 % ) underwent repeat intervention , including positioning of the proximal cuff in 8 patients and late conversion to open repair in five patients . Of the nine variables examined with multivariate analysis , only 3 , ie , presence of neck circumferential thrombus ( hazard ratio [ HR ] , 2.51 ; 95 % confidence interval [ CI ] , 1.26 - 5.01 ; P = .008 ) , preoperative proximal neck diameter ( HR , 1.21 ; 95 % CI , 1.07 - 135 ; P = .001 ) , and preoperative AAA diameter ( HR , 1.03 ; 95 % CI , 1.00 - 1.06 ; P = .046 ) were positive independent predictors of AND , whereas the other 6 , ie , neck angulation more than 60 degrees , neck length , suprarenal fixation , oversizing more than 15 % , endoleak at 30 days , and increased AAA diameter during follow-up , showed no significant correlation . Probability of AND at 48 months was 59 + /- 6.1 at analysis with the Kaplan-Meier method . CONCLUSIONS AND is a frequent sequela of endoluminal repair in the mid-term . Severe AND developed in a small percentage of our patients , compromising integrity of AAA repair . Patients with large aneurysms and aortic necks and patients with aortic neck circumferential thrombus are at high risk for aortic neck enlargement after endoluminal repair of AAA |
2,217 | 21,849,376 | Conclusion : Whole body vibration is beneficial for enhancing leg muscle strength among older adults .
However , the review suggests that whole body vibration has no overall treatment effect on bone mineral density in older women .
No r and omized trial has examined the effects of whole body vibration on bone mineral density in older men | Objective : A systematic review and meta- analysis of r and omized controlled trials was undertaken to determine whether whole body vibration improves bone mineral density and leg muscle strength in older adults . | OBJECTIVE To investigate the efficacy of high-frequency whole-body vibration ( WBV ) on balancing ability in elderly women . DESIGN R and omized controlled trial . Subjects were r and omized to either the WBV intervention or the no-treatment control group . SETTING Community-living elderly women . PARTICIPANTS Sixty-nine elderly women aged 60 or above without habitual exercise . INTERVENTION Side alternating WBV at 20Hz with 3 minutes a day and 3 days a week for 3 months in the WBV intervention group . Those in control group remained sedentary with normal daily life for the whole study period . MAIN OUTCOME MEASURES Limits of stability in terms of reaction time , movement velocity , directional control , endpoint excursion , maximum excursion , and the functional reach test were performed at baseline and endpoint . RESULTS Significant enhancement of stability was detected in movement velocity ( P<.01 ) , maximum point excursion ( P<.01 ) , in directional control ( P<.05 ) . CONCLUSIONS WBV was effective in improving the balancing ability in elderly women . This also provides evidence to support our user-friendly WBV treatment protocol of 3 minutes a day for the elderly to maintain their balancing ability and reduce risks of fall OBJECTIVES To investigate the effects of 24 weeks of whole-body-vibration ( WBV ) training on knee-extension strength and speed of movement and on counter-movement jump performance in older women . DESIGN A r and omized , controlled trial . SETTING Exercise Physiology and Biomechanics Laboratory , Leuven , Belgium . PARTICIPANTS Eighty-nine postmenopausal women , off hormone replacement therapy , aged 58 to 74 , were r and omly assigned to a WBV group ( n=30 ) , a resistance-training group ( RES , n=30 ) , or a control group ( n=29 ) . INTERVENTION The WBV group and the RES group trained three times a week for 24 weeks . The WBV group performed unloaded static and dynamic knee-extensor exercises on a vibration platform , which provokes reflexive muscle activity . The RES group trained knee-extensors by performing dynamic leg-press and leg-extension exercises increasing from low ( 20 repetitions maximum ( RM ) ) to high ( 8RM ) resistance . The control group did not participate in any training . MEASUREMENTS Pre- , mid- ( 12 weeks ) , and post- ( 24 weeks ) isometric strength and dynamic strength of knee extensors were measured using a motor-driven dynamometer . Speed of movement of knee extension was assessed using an external resistance equivalent to 1 % , 20 % , 40 % , and 60 % of isometric maximum . Counter-movement jump performance was determined using a contact mat . RESULTS Isometric and dynamic knee extensor strength increased significantly ( P<.001 ) in the WBV group ( mean+/-st and ard error 15.0+/-2.1 % and 16.1+/-3.1 % , respectively ) and the RES group ( 18.4+/-2.8 % and 13.9+/-2.7 % , respectively ) after 24 weeks of training , with the training effects not significantly different between the groups ( P=.558 ) . Speed of movement of knee extension significantly increased at low resistance ( 1 % or 20 % of isometric maximum ) in the WBV group only ( 7.4+/-1.8 % and 6.3+/-2.0 % , respectively ) after 24 weeks of training , with no significant differences in training effect between the WBV and the RES groups ( P=.391 ; P=.142 ) . Counter-movement jump height enhanced significantly ( P<.001 ) in the WBV group ( 19.4+/-2.8 % ) and the RES group ( 12.9+/-2.9 % ) after 24 weeks of training . Most of the gain in knee-extension strength and speed of movement and in counter-movement jump performance had been realized after 12 weeks of training . CONCLUSION WBV is a suitable training method and is as efficient as conventional RES training to improve knee-extension strength and speed of movement and counter-movement jump performance in older women . As previously shown in young women , it is suggested that the strength gain in older women is mainly due to the vibration stimulus and not only to the unloaded exercises performed on the WBV platform OBJECTIVE To test whether training on a high-frequency ( 28Hz ) vibrating platform improves muscle power and bone characteristics in postmenopausal women . DESIGN R and omized controlled trial with 6-month follow-up . SETTING Outpatient clinic in a general hospital in Italy . PARTICIPANTS Twenty-nine postmenopausal women ( intervention group , n=14 ; matched controls , n=15 ) . INTERVENTION Participants stood on a ground-based oscillating platform for three 2-minute sessions for a total of 6 minutes per training session , twice weekly for 6 months . The controls did not receive any training . Both groups were evaluated at baseline and after 6 months . MAIN OUTCOME MEASURES Muscle power , calculated from ground reaction forces produced by l and ing after jumping as high as possible on a forceplate , cortical bone density , and biomarkers of bone turnover . RESULTS Over 6 months , muscle power improved by about 5 % in women who received the intervention , and it remained unchanged in controls ( P=.004 ) . Muscle force remained stable in both the intervention and control groups . No significant changes were observed in bone characteristics . CONCLUSION Reflex muscular contractions induced by vibration training improve muscle power in postmenopausal women According to experimental studies , low-amplitude high-frequency vibration is anabolic to bone tissue , whereas in clinical trials , the bone effects have varied . Given the potential of whole body vibration in bone training , this study aim ed at exploring the transmission of vertical sinusoidal vibration to the human body over a wide range of applicable amplitudes ( from 0.05 to 3 mm ) and frequencies ( from 10 to 90 Hz ) . Vibration-induced accelerations were assessed with skin-mounted triaxial accelerometers at the ankle , knee , hip , and lumbar spine in four males st and ing on a high-performance vibration platform . Peak vertical accelerations of the platform covered a range from 0.04 to 19 in units of G ( Earth 's gravitational constant ) . Substantial amplification of peak acceleration could occur between 10 and 40 Hz for the ankle , 10 and 25 Hz for the knee , 10 and 20 Hz for the hip , and at 10 Hz for the spine . Beyond these frequencies , the transmitted vibration power declined to 1/10th-1/1000 th of the power delivered by the platform . Transmission of vibration to the body is a complicated phenomenon because of nonlinearities in the human musculoskeletal system . These results may assist in estimating how the transmission of vibration-induced accelerations to body segments is modified by amplitude and frequency and how well the sinusoidal waveform is maintained . Although the attenuation of vertical vibration at higher frequencies is fortunate from the aspect of safety , amplitudes > 0.5 mm may result in greater peak accelerations than imposed at the platform and thus pose a potential hazard for the fragile musculoskeletal system Background Whole-body vibration ( WBV ) is a new type of exercise that has been increasingly tested for the ability to prevent bone fractures and osteoporosis in frail people . There are two currently marketed vibrating plates : a ) the whole plate oscillates up and down ; b ) reciprocating vertical displacements on the left and right side of a fulcrum , increasing the lateral accelerations . A few studies have shown recently the effectiveness of the up- and -down plate for increasing Bone Mineral Density ( BMD ) and balance ; but the effectiveness of the reciprocating plate technique remains mainly unknown . The aim was to compare the effects of WBV using a reciprocating platform at frequencies lower than 20 Hz and a walking-based exercise programme on BMD and balance in post-menopausal women . Methods Twenty-eight physically untrained post-menopausal women were assigned at r and om to a WBV group or a Walking group . Both experimental programmes consisted of 3 sessions per week for 8 months . Each vibratory session included 6 bouts of 1 min ( 12.6 Hz in frequency and 3 cm in amplitude with 60 ° of knee flexion ) with 1 min rest between bouts . Each walking session was 55 minutes of walking and 5 minutes of stretching . Hip and lumbar BMD ( g·cm-2 ) were measured using dual-energy X-ray absorptiometry and balance was assessed by the blind flamingo test . ANOVA for repeated measurements was adjusted by baseline data , weight and age . Results After 8 months , BMD at the femoral neck in the WBV group was increased by 4.3 % ( P = 0.011 ) compared to the Walking group . In contrast , the BMD at the lumbar spine was unaltered in both groups . Balance was improved in the WBV group ( 29 % ) but not in the Walking group . Conclusion The 8-month course of vibratory exercise using a reciprocating plate is feasible and is more effective than walking to improve two major determinants of bone fractures : hip BMD and balance This study was design ed to investigate the effects of vibration on muscle performance and mobility in a healthy , untrained , older population . Forty-three participants ( 23 men , 20 women , 66 - 85 y old ) performed tests of sit-to-st and ( STS ) , 5- and 10-m fast walk , timed up- and -go test , stair mobility , and strength . Participants were r and omly assigned to a vibration group , an exercise-withoutvibration group , or a control group . Training consisted of 3 sessions/wk for 2 mo . After training , the vibration and exercise groups showed improved STS ( 12.4 % , 10.2 % ) , 5-m fast walk ( 3.0 % , 3.7 % ) , and knee-extension strength ( 8.1 % , 7.2 % ) compared with the control ( p < 0.05 ) . Even though vibration training improved lower limb strength , it did not appear to have a facilitatory effect on functional-performance tasks compared with the exercise-without-vibration group . Comparable mobility and performance changes between the experimental groups suggest that improvements are linked with greater knee-extension strength and largely attributed to the unloaded squats performed by both exercise groups To determine whether 10 weeks of whole-body vibration ( WBV ) training has a significant effect on strength , muscle mass , muscle power , and mobility in older women , 26 subjects were r and omly assigned to a WBV training group ( n=13 ; mean age 79 years ) and a control ( CON ) group ( n=13 ; mean age 76 years ) . Maximal voluntary isometric contraction ( MVIC ) increased 38.8 % in the WBV group , without changes in the CON group . Electromyographic activity of the vastus medialis ( VM ) , the vastus lateralis , and the biceps femoris ( BF ) did not change in either group . Thigh muscle cross-sectional area increased significantly after training in VM ( 8.7 % ) and BF ( 15.5 % ) . Muscle power at 20 % , 40 % , and 60 % MVIC decreased from pre-test to post-test in the CON group ; however , WBV training prevented the decrease in the WBV group . Consequently , mobility , measured by the Timed Up and Go test , increased significantly after training ( 9.0 % ) only in the WBV group . Ten weeks of lower limb WBV training in older women produces a significant increase in muscle strength induced by thigh muscle hypertrophy , with no change in muscle power . The adaptations to WBV found in the present study may be of use in counteracting the loss of muscle strength and mobility associated with age-induced sarcopenia Background and aims : Exercise may enhance the effect of alendronate on bone mineral density ( BMD ) and reduce chronic back pain in elderly women with osteoporosis . The aim of this study was to determine whether whole-body vibration exercise would enhance the effect of alendronate on lumbar BMD and bone turnover , and reduce chronic back pain in post-menopausal women with osteoporosis . Methods : Fifty post-menopausal women with osteoporosis , 55–88 years of age , were r and omly divided into two groups of 25 patients each : one taking alendronate ( 5 mg daily , ALN ) and one taking alendronate plus exercise ( ALN+EX ) . Exercise consisted of whole-body vibration using a Galileo machine ( Novotec , Pforzheim , Germany ) , at an intensity of 20 Hz , frequency once a week , and duration of exercise 4 minutes . The study lasted 12 months . Lumbar BMD was measured by dual energy X-ray absorptiometry ( Hologic QDR 1500W ) . Urinary cross-linked N-terminal telopeptides of type I collagen ( NTX ) and serum alkaline phos-phatase ( ALP ) levels were measured by enzyme-linked immunosorbent assay and st and ard laboratory techniques , respectively . Chronic back pain was evaluated by face scale score at baseline and every 6 months . Results : There were no significant differences in baseline characteristics , including age , body mass index , years since menopause , lumbar BMD , urinary NTX and serum ALP levels , or face scale score between the two groups . The increase in lumbar BMD and the reduction in urinary NTX and serum ALP levels were similar in the ALN and ALN+EX groups . However , the reduction in chronic back pain was greater in the ALN+EX group than in the ALN group . Conclusions : The results of this study suggest that whole-body vibration exercise using a Galileo machine appears to be useful in reducing chronic back pain , probably by relaxing the back muscles in post-menopausal osteoporotic women treated with alendronate PURPOSE The aim of this study was to investigate and to compare the effect of a 12-wk period of whole-body vibration training and resistance training on human knee-extensor strength . METHODS Sixty-seven untrained females ( 21.4 + /- 1.8 yr ) participated in the study . The whole-body vibration group ( WBV , N = 18 ) and the placebo group ( PL , N = 19 ) performed static and dynamic knee-extensor exercises on a vibration platform . The acceleration of the vibration platform was between 2.28 g and 5.09 g , whereas only 0.4 g for the PL condition . Vibration ( 35 - 40 Hz ) result ed in increased EMG activity , but the EMG signal remained unchanged in the PL condition . The resistance-training group ( RES , N = 18 ) trained knee extensors by dynamic leg-press and leg-extension exercises ( 10 - 20 RM ) . All training groups exercised 3x wk-1 . The control group ( CO , N = 12 ) did not participate in any training . Pre- and postisometric , dynamic , and ballistic knee-extensor strength were measured by means of a motor-driven dynamometer . Explosive strength was determined by means of a counter-movement jump . RESULTS Isometric and dynamic knee-extensor strength increased significantly ( P < 0.001 ) in both the WBV group ( 16.6 + /- 10.8 % ; 9.0 + /- 3.2 % ) and the RES group ( 14.4 + /- 5.3 % ; 7.0 + /- 6.2 % ) , respectively , whereas the PL and CO group showed no significant ( P > 0.05 ) increase . Counter-movement jump height enhanced significantly ( P < 0.001 ) in the WBV group ( 7.6 + /- 4.3 % ) only . There was no effect of any of the interventions on maximal speed of movement , as measured by means of ballistic tests . CONCLUSIONS WBV , and the reflexive muscle contraction it provokes , has the potential to induce strength gain in knee extensors of previously untrained females to the same extent as resistance training at moderate intensity . It was clearly shown that strength increases after WBV training are not attributable to a placebo effect BACKGROUND This r and omized controlled study investigated the effects of 1-year whole-body vibration ( WBV ) training on isometric and explosive muscle strength and muscle mass in community-dwelling men older than 60 years . METHODS Muscle characteristics of the WBV group ( n = 31 , 67.3 + /- 0.7 years ) were compared with those of a fitness ( FIT ) group ( n = 30 , 67.4 + /- 0.8 years ) and a control ( CON ) group ( n = 36 , 68.6 + /- 0.9 years ) . Isometric strength of the knee extensors was measured using an isokinetic dynamometer , explosive muscle strength was assessed using a counter movement jump , and muscle mass of the upper leg was determined by computed tomography . RESULTS Isometric muscle strength , explosive muscle strength , and muscle mass increased significantly in the WBV group ( 9.8 % , 10.9 % , and 3.4 % , respectively ) and in the FIT group ( 13.1 % , 9.8 % , and 3.8 % , respectively ) with the training effects not significantly different between the groups . No significant changes in any parameter were found in the CON group . CONCLUSION WBV training is as efficient as a fitness program to increase isometric and explosive knee extension strength and muscle mass of the upper leg in community-dwelling older men . These findings suggest that WBV training has potential to prevent or reverse the age-related loss in skeletal muscle mass , referred to as sarcopenia The aim of this study was to investigate the effects of whole-body vibrations ( WBV ) on the mechanical behaviour of human skeletal muscle . For this purpose , six female volleyball players at national level were recruited voluntarily . They were tested with maximal dynamic leg press exercise on a slide machine with extra loads of 70 , 90 , 110 and 130 kg . After the testing , one leg was r and omly assigned to the control treatment ( C ) and the other to the experimental treatment ( E ) consisting of vibrations . The subjects were then retested at the end of the treatment using the leg press . Results showed remarkable and statistically significant enhancement of the experimental treatment in average velocity ( AV ) , average force ( AF ) and average power ( AP ) ( P < 0.05 - 0.005 ) . Consequently , the velocity-force and power-force relationship shifted to the right after the treatment . In conclusion , it was affirmed that the enhancement could be caused by neural factors , as athletes were well accustomed to the leg press exercise and the learning effect was minimized Bed rest is a recognized model for muscle atrophy and bone loss in space flight and in clinical medicine . We hypothesized that whole body vibration in combination with resistive exercise ( RVE ) would be an effective countermeasure . Twenty healthy male volunteers underwent horizontal bed rest for 56 days and were r and omly assigned either to a group that performed RVE 11 times per week or to a group that underwent bed rest only ( Ctrl ) . Bone mineral content ( BMC ) was assessed by peripheral quantitative computed tomography ( pQCT ) in the tibia and the radius and by dual x-ray absorptiometry ( DXA ) in the hip and lumbar spine at baseline and at regular intervals during bed rest and a 12-month follow-up . RVE appeared to protect muscle size and function , and it also prevented bone loss ( p-values between < 0.001 and 0.01 ) . Bone losses were largest in the distal tibia epiphysis , where BMC declined from 421.8 mg/mm ( SD 51.3 ) to 406.6 mg/mm ( SD 52.7 ) in Ctrl , but only from 411.1 mg/mm ( SD 56.6 ) to 409.6 mg/mm ( SD 66.7 ) in RVE . Most of the BMC losses were recovered by 12-month follow-up . Analyses showed that the epiphyseal cortex , rather than spongiosa , depicted the most pronounced changes during bed rest and recovery . These results suggest that the combined countermeasure applied in this study is effective to prevent bone losses from the tibia . This underlines the importance of mechanical usage for the maintenance of the human skeleton OBJECTIVES To determine the effect of two different community-based group exercise programs on functional balance , mobility , postural reflexes , and falls in older adults with chronic stroke . DESIGN A r and omized , clinical trial . SETTING Community center . PARTICIPANTS Sixty-one community-dwelling older adults with chronic stroke . INTERVENTION Participants were r and omly assigned to an agility ( n=30 ) or stretching/weight-shifting ( n=31 ) exercise group . Both groups exercised three times a week for 10 weeks . MEASUREMENTS Participants were assessed before , immediately after , and 1 month after the intervention for Berg Balance , Timed Up and Go , step reaction time , Activities-specific Balance Confidence , and Nottingham Health Profile . Testing of st and ing postural reflexes and induced falls evoked by a translating platform was also performed . In addition , falls in the community were tracked for 1 year from the start of the interventions . RESULTS Although exercise led to improvements in all clinical outcome measures for both groups , the agility group demonstrated greater improvement in step reaction time and paretic rectus femoris postural reflex onset latency than the stretching/weight-shifting group . In addition , the agility group experienced fewer induced falls on the platform . CONCLUSION Group exercise programs that include agility or stretching/weight shifting exercises improve postural reflexes , functional balance , and mobility and may lead to a reduction of falls in older adults with stroke BACKGROUND whole body vibration ( WBV ) training appears to be an efficient alternative for conventional resistance training in older individuals . So far , no data exist about the vibratory effect on cardiorespiratory fitness . OBJECTIVES this r and omised controlled trial assessed the effects of 1-year WBV training on cardiorespiratory fitness and muscle strength in community-dwelling adults over the age of 60 . METHODS a total of 220 adults ( mean age 67.1 years ) were r and omly assigned to a WBV group , fitness group or control group . The WBV group exercised on a vibration platform , and the fitness group performed cardiovascular , resistance , balance and stretching exercises . The control group did not participate in any training . Heart rate was measured during a single WBV session . Peak oxygen uptake ( VO(2peak ) ) and time-to-peak exercise ( TPE ) were measured during progressive bicycle ergometry . Muscle strength was assessed by a dynamometer . RESULTS heart rate increased significantly during WBV training . After 1 year , VO(2peak ) , TPE and muscle strength increased significantly in the WBV and fitness groups . Both training groups improved similarly in VO(2peak ) and muscle strength . The fitness group improved significantly more in TPE than the WBV group . CONCLUSION WBV training in community-dwelling elderly appears to be efficient to improve cardiorespiratory fitness and muscle strength OBJECTIVE The objective of this study was to investigate efficacy of a whole-body vibration ( WBV ) intervention on functional performance of community-dwelling older adults . DESIGN The study was design ed as a r and omized controlled trial . SETTING The setting was in community centers . SUBJECTS There were 37 total subjects ( 21 women and 16 men ) ( age 69 + /- 8 years ; mean + /- st and ard deviation ) . INTERVENTION Participants were r and omized to a WBV intervention ( INT ) group and control ( CON ) group . Whole-body vibration was administered for five 1-minute bouts per session , 3 days per week , for 6 weeks . The CON group was asked not to commence any form of physical training . OUTCOME MEASURES Functional performance was measured with the timed-up- and -go-test ( TUG ) and sit-to-st and -test ( STS ) . RESULTS After WBV , TUG and STS time was less for INT than CON ( INT , TUG 7.6 + /- 0.3 seconds , STS 11.9 + /- 2.0 seconds ; CON , TUG 8.6 + /- 0.9 , STS 13.5 + /- 1.1 seconds ; p < 0.05 ) . Within INT , TUG improved 0.9 + /- 0.4 seconds ; p = 0.01 and STS improved 3.0 + /- 0.9 seconds ; p = 0.05 ) . CONCLUSIONS The efficacy of this WBV intervention was established . Functional performance improvement after WBV may be attributed to a number of biological mechanisms that remain speculative . Further research is required to mechanistically underst and the effects of WBV on older adults The aim of this study was to investigate the effects of vibration exercise on postural steadiness performance in a healthy , older population . Forty-three healthy , older participants ( 23 men and 20 women , aged 73.5+/-4.5 yr ) were r and omly assigned to either a vibration group ( VIB ) , an exercise without vibration group ( EX ) or a control group ( CONT ) . The VIB and EX groups undertook static and dynamic bodyweight exercises three times per week for eight weeks . Static balance was assessed using a one-legged postural steadiness ( OLPS ) test . This test was performed prior to and immediately after the training period . OLPS improved significantly for the VIB intervention after eight weeks training ( p<0.05 ) compared to the EX and CONT groups . The improvements in OLPS were significantly affected by the baseline values , with the largest changes evident for VIB participants with a poorer initial score ( p<0.01 ) . Vibration exercise can contribute to improved static one-legged balance in a healthy , older population . As improvements in OLPS were related to baseline values , vibration exercise as an intervention would appear to serve the most benefit for those that exhibit diminished postural control OBJECTIVE To investigate the effects of whole body vibration in the elderly . DESIGN R and omized controlled trial . SETTING Nursing home . PARTICIPANTS Forty-two elderly volunteers . INTERVENTIONS Six-week vibration intervention plus physical therapy ( PT ) ( n=22 ) or PT alone ( n=20 ) . MAIN OUTCOME MEASURES We assessed gait and body balance using the Tinetti test ( maximum scores of 12 for gait , 16 for body balance , 28 for global score ) , motor capacity using the Timed Up & Go ( TUG ) test , and health-related quality of life ( HRQOL ) using the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) . RESULTS After 6 weeks , the vibration intervention group improved by a mean + /- st and ard deviation of 2.4+/-2.3 points on the gait score compared with no score change in the control group ( P < .001 ) . The intervention group improved by 3.5+/-2.1 points on the body balance score compared with a decrease of 0.3+/-1.2 points in the control group ( P < .001 ) . TUG test time decreased by 11.0+/-8.6 seconds in the treated group compared with an increase of 2.6+/-8.8 seconds in the control group ( P < .001 ) . The intervention group had significantly greater improvements from baseline on 8 of 9 items on the SF-36 compared with the control group . CONCLUSIONS Controlled whole body vibration can improve elements of fall risk and HRQOL in elderly patients UNLABELLED High-frequency mechanical strain seems to stimulate bone strength in animals . In this r and omized controlled trial , hip BMD was measured in postmenopausal women after a 24-week whole body vibration ( WBV ) training program . Vibration training significantly increased BMD of the hip . These findings suggest that WBV training might be useful in the prevention of osteoporosis . INTRODUCTION High-frequency mechanical strain has been shown to stimulate bone strength in different animal models . However , the effects of vibration exercise on the human skeleton have rarely been studied . Particularly in postmenopausal women-who are most at risk of developing osteoporosis-r and omized controlled data on the safety and efficacy of vibration loading are lacking . The aim of this r and omized controlled trial was to assess the musculoskeletal effects of high-frequency loading by means of whole body vibration ( WBV ) in postmenopausal women . MATERIAL S AND METHODS Seventy volunteers ( age , 58 - 74 years ) were r and omly assigned to a whole body vibration training group ( WBV , n = 25 ) , a resistance training group ( RES , n = 22 ) , or a control group ( CON , n = 23 ) . The WBV group and the RES group trained three times weekly for 24 weeks . The WBV group performed static and dynamic knee-extensor exercises on a vibration platform ( 35 - 40 Hz , 2.28 - 5.09 g ) , which mechanically loaded the bone and evoked reflexive muscle contractions . The RES group trained knee extensors by dynamic leg press and leg extension exercises , increasing from low ( 20 RM ) to high ( 8 RM ) resistance . The CON group did not participate in any training . Hip bone density was measured using DXA at baseline and after the 6-month intervention . Isometric and dynamic strength were measured by means of a motor-driven dynamometer . Data were analyzed by means of repeated measures ANOVA . RESULTS No vibration-related side effects were observed . Vibration training improved isometric and dynamic muscle strength ( + 15 % and + 16 % , respectively ; p < 0.01 ) and also significantly increased BMD of the hip ( + 0.93 % , p < 0.05 ) . No changes in hip BMD were observed in women participating in resistance training or age-matched controls ( -0.60 % and -0.62 % , respectively ; not significant ) . Serum markers of bone turnover did not change in any of the groups . CONCLUSION These findings suggest that WBV training may be a feasible and effective way to modify well-recognized risk factors for falls and fractures in older women and support the need for further human studies In this study , we compared the efficacy of 8 months of low-frequency vibration and a walk-based program in health-related fitness . Twenty-seven postmenopausal women were r and omly assigned into two groups : whole-body vibration ( WBV ) group ( n = 18 ) performed three times/week a static exercise on a vibration platform ( 6 sets of 1-min with 1 min of rest , with a 12.6 Hz of frequency and an amplitude of 3 mm ) ; walk-based program ( WP ) group ( n = 18 ) performed three times/week a 60-min of walk activity at 70–75 % of maximal heart rate . A health-related battery of tests was applied . Maximal unilateral concentric and eccentric isokinetic torque of the knee extensors was recorded by an isokinetic dynamometer . Physical fitness was measured using the following tests : vertical jump test , chair rise test and maximal walking speed test over 4 m. Maximal unilateral isokinetic strength was measured in the knee extensors in concentric actions at 60 and 300 ° /s , and eccentric action at 60 ° /s . After 8 months , the WP improved the time spent to walk 4 m ( 20 % ) and to perform the chair rise test ( 12 % ) compared to the WBV group ( P = 0.006 , 0.002 , respectively ) . In contrast , the comparison of the changes in vertical jump showed the higher effectiveness of the vibratory exercise in 7 % ( P = 0.025 ) . None of exercise programs showed change on isokinetic measurements . These results indicate that both programs differed in the main achievements and could be complementary to prevent lower limbs muscle strength decrease as we age [ IS RCT N76235671 ] Recent animal studies have given evidence that vibration loading may be an efficient and safe way to improve mass and mechanical competence of bone , thus providing great potential for preventing and treating osteoporosis . R and omized controlled trials on the safety and efficacy of the vibration on human skeleton are , however , lacking . This r and omized controlled intervention trial was design ed to assess the effects of an 8-month whole body vibration intervention on bone , muscular performance , and body balance in young and healthy adults . Fifty-six volunteers ( 21 men and 35 women ; age , 19 - 38 years ) were r and omly assigned to the vibration group or control group . The vibration intervention consisted of an 8-month whole body vibration ( 4 min/day , 3 - 5 times per week ) . During the 4-minute vibration program , the platform oscillated in an ascending order from 25 to 45 Hz , corresponding to estimated maximum vertical accelerations from 2 g to 8 g. Mass , structure , and estimated strength of bone at the distal tibia and tibial shaft were assessed by peripheral quantitative computed tomography ( pQCT ) at baseline and at 8 months . Bone mineral content was measured at the lumbar spine , femoral neck , trochanter , calcaneus , and distal radius using DXA at baseline and after the 8-month intervention . Serum markers of bone turnover were determined at baseline and 3 , 6 , and 8 months . Five performance tests ( vertical jump , isometric extension strength of the lower extremities , grip strength , shuttle run , and postural sway ) were performed at baseline and after the 8-month intervention . The 8-month vibration intervention succeeded well and was safe to perform but had no effect on mass , structure , or estimated strength of bone at any skeletal site . Serum markers of bone turnover did not change during the vibration intervention . However , at 8 months , a 7.8 % net benefit in the vertical jump height was observed in the vibration group ( 95 % CI , 2.8 - 13.1 % ; p = 0.003 ) . On the other performance and balance tests , the vibration intervention had no effect . In conclusion , the studied whole body vibration program had no effect on bones of young , healthy adults , but instead , increased vertical jump height . Future human studies are needed before clinical recommendations for vibration exercise Bedient , AM , Adams , JB , Edwards , DA , Serravite , DH , Huntsman , E , Mow , SE , Roos , BA , and Signorile , JF . Displacement and frequency for maximizing power output result ing from a bout of whole-body vibration . J Strength Cond Res 23(6 ) : 1683 - 1687 , 2009-Whole-body vibration ( WBV ) has been shown to be effective for increasing lower-body power ; however , the combination of frequency , displacement , and duration that elicits the best acute response has yet to be determined . The purpose of this study was to identify the protocol eliciting the greatest improvement in power after an acute bout of WBV . Forty men and women participated in this study , in which 8 different combinations of 30 , 35 , 40 , and 50 Hz with 2-mm and 5-mm displacements were tested over 3 days . For all protocol s , r and omized to reduce potential order effects , subjects underwent 30 seconds of WBV while holding an isometric squat at a knee angle of 2.27 rad . Power was assessed by countermovement jumps . Subjects performed 3 jumps before WBV , immediately afterward , and 1 , 5 , and 10 minutes later . The highest normalized peak power ( nPP ) at each time point was determined using a 4 ( frequency ) × 2 ( displacement ) × 5 ( time ) repeated- measures analysis of variance . Significant effects were seen for frequency ( p ≤ 0.026 ) and time ( p ≤ .0001 ) . Post hoc analyses revealed that the 30-Hz condition ( 1.010 ± 0.003 ) produced a higher nPP than 35 Hz ( 1.00 ± 0.003 , p ≤ 0.026 ) and 40 Hz ( 1.002 ± 0.002 , p ≤ 0.028 ) but not 50 Hz ( 1.004 ± .002 ) . We also found a significantly higher nPP for the 1-minute post-treatment time point ( 1.011 ± .0003 ) vs. all other time points ( p ≤ 0.006 ) . Our data show that an acute WBV bout can significantly increase power output at 1 minute post-treatment across all frequencies and displacements , although 30 Hz appears to have a greater effect on power output than either 35 Hz or 40 Hz , but not 50 Hz , at all post-treatment time points Furness , TP and Maschette , WE . Influence of whole body vibration platform frequency on neuromuscular performance of community-dwelling older adults . J Strength Cond Res 23(5 ) : 1508 - 1513 , 2009-The purpose of this study was to progressively overload vibration platform frequency to describe sea-saw whole body vibration influence on neuromuscular performance of community-dwelling older adults . Seventy-three community-dwelling older adults ( aged 72 ± 8 years ) were r and omly assigned to 4 groups ( zero , one , 2 , and 3 whole body vibration sessions per week ) . Quantifiers of neuromuscular performance such as the 5-Chair St and s test , the Timed Up and Go ( TUG ) test , and the Tinetti test were recorded . Furthermore , Health-related quality of life was qualified with the SF-36 Health Survey . A 6-week whole body vibration intervention significantly improved the quantifiers of neuromuscular performance in a community-dwelling older adult sample . Whole body vibration was shown to significantly reduce time taken to complete the 5-Chair St and s test ( p < 0.05 ) and the TUG test ( p < 0.05 ) . Tinetti test scores significantly improved ( p < 0.05 ) . as did all components of health-related quality of life ( p < 0.05 ) . Overall , progressively overloaded frequency elicited more beneficial improvement for the 3 whole body vibration sessions per week group . It was concluded that progressively overloaded frequency was effective in improving quantifiable measures of neuromuscular performance in the sample and that practitioners may confidently prescribe 3 whole body vibration sessions per week with more precise knowledge of the effects of whole body vibration on neuromuscular performance and health-related quality -of-life effects To study risk factors for falling , we conducted a one-year prospect i ve investigation , using a sample of 336 persons at least 75 years of age who were living in the community . All subjects underwent detailed clinical evaluation , including st and ardized measures of mental status , strength , reflexes , balance , and gait ; in addition , we inspected their homes for environmental hazards . Falls and their circumstances were identified during bimonthly telephone calls . During one year of follow-up , 108 subjects ( 32 percent ) fell at least once ; 24 percent of those who fell had serious injuries and 6 percent had fractures . Predisposing factors for falls were identified in linear-logistic models . The adjusted odds ratio for sedative use was 28.3 ; for cognitive impairment , 5.0 ; for disability of the lower extremities , 3.8 ; for palmomental reflex , 3.0 ; for abnormalities of balance and gait , 1.9 ; and for foot problems , 1.8 ; the lower bounds of the 95 percent confidence intervals were 1 or more for all variables . The risk of falling increased linearly with the number of risk factors , from 8 percent with none to 78 percent with four or more risk factors ( P less than 0.0001 ) . About 10 percent of the falls occurred during acute illness , 5 percent during hazardous activity , and 44 percent in the presence of environmental hazards . We conclude that falls among older persons living in the community are common and that a simple clinical assessment can identify the elderly persons who are at the greatest risk of falling 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 . UNLABELLED Age-related changes in body composition are well-documented with a decrease in lean body mass and a redistribution of body fat generally observed . Resistance training alone has been shown to have positive effects on body composition , however , these benefits may be enhanced by the addition of a vibration stimulus . OBJECTIVE The purpose of this study was to determine the effects of 8 months of resistance training with and without whole-body vibration ( WBV ) on body composition in sedentary postmenopausal women . METHODS Fifty-five women were assigned to resistance only ( RG , n=22 ) , vibration plus resistance ( VR , n=21 ) or non-exercising control ( CG , n=12 ) groups . Resistance training ( 3 sets 10 repetitions 80 % strength ) was performed using isotonic weight training equipment and whole-body vibration was done with the use of the power plate ( Northbrooke , IL ) vibration platform for three times per week for 8 months . Total and regional body composition was assessed from the total body DXA scans at baseline ( pre ) and after 8 months ( post ) of training . RESULTS In the VR group , total % body fat decreased from pre- to post-time points ( p<0.05 ) , whereas , the CG group had a significant increase in total % body fat ( p<0.05 ) . Both training groups exhibited significant increases in bone free lean tissue mass for the total body , arm and trunk regions from pre to post ( p<0.05 ) . CG did not show any changes in lean tissue . CONCLUSION In older women , resistance training alone and with whole-body vibration result ed in positive body composition changes by increasing lean tissue . However , only the combination of resistance training and whole-body vibration was effective for decreasing percent body fat OBJECTIVES To examine the effects of a community-based group exercise program for older individuals with chronic stroke . DESIGN Prospect i ve , single-blind , r and omized , controlled intervention trial . SETTING Intervention was community-based . Data collection was performed in a research laboratory located in a rehabilitation hospital . PARTICIPANTS Sixty-three older individuals ( aged > or = 50 ) with chronic stroke ( poststroke duration > or = 1 year ) who were living in the community . INTERVENTION Participants were r and omized into intervention group ( n=32 ) or control group ( n=31 ) . The intervention group underwent a fitness and mobility exercise ( FAME ) program design ed to improve cardiorespiratory fitness , mobility , leg muscle strength , balance , and hip bone mineral density ( BMD ) ( 1-hour sessions , three sessions/week , for 19 weeks ) . The control group underwent a seated upper extremity program . MEASUREMENTS Cardiorespiratory fitness ( maximal oxygen consumption ) , mobility ( 6-minute walk test ) , leg muscle strength ( isometric knee extension ) , balance ( Berg Balance Scale ) , activity and participation ( Physical Activity Scale for Individuals with Physical Disabilities ) , and femoral neck BMD ( using dual-energy x-ray absorptiometry ) . RESULTS The intervention group had significantly more gains in cardiorespiratory fitness , mobility , and paretic leg muscle strength than controls . Femoral neck BMD of the paretic leg was maintained in the intervention group , whereas a significant decline of the same occurred in controls . There was no significant time-by-group interaction for balance , activity and participation , nonparetic leg muscle strength , or nonparetic femoral neck BMD . CONCLUSION The FAME program is feasible and beneficial for improving some of the secondary complications result ing from physical inactivity in older adults living with stroke . It may serve as a good model of a community-based fitness program for preventing secondary diseases in older adults living with chronic conditions It was hypothesized that both vibration frequency and muscle length modulate the strengthening of muscles that is assumed to result from whole-body vibration ( WBV ) . Length of knee extensor muscles during vibration is affected by the knee joint angle ; the lengths of the knee extensors increase with more flexed knee joint angles . In an intervention study 28 volunteers were r and omly assigned to 1 of 4 groups . Each group received 4 weeks of WBV at 1 of 3 different frequencies ( 20 , 27 , or 34 Hz ) or 1 of 2 different lengths of knee extensors . Voluntary , isometric knee extension moment-angle relationship was determined . Initially , stronger subjects reacted differently to WBV than weaker participants . In stronger subjects knee extension moment did not improve ; in the weaker subjects considerable improvements were observed ranging from 10 to 50 % . Neither vibration frequency nor muscle length during the intervention affected the improvements . In addition to strength , the knee joint angle at which the maximal joint moment was generated ( optimal joint angle ) was affected . When trained at short muscle lengths , optimal angle shifted to more extend joint position . WBV training at long muscle lengths tended to induce an opposite shift . The amount of this shift tended to be influenced by vibration frequency ; the lower the vibration frequency the larger the shift . Shifts of optimal lengths occurred in both weaker and stronger subjects . This study shows that muscle length during training affects the angle of knee joint at which the maximal extension moment was generated . Moreover , in weaker subjects WBV result ed in higher maximal knee joint extension moments . Vibration frequency and muscle length during vibration did not affect this joint moment gain Summary We determined whether the effect of exercise on bone mineral density ( BMD ) and falls can be enhanced by whole body vibration ( WBV ) . In summary , the multi- purpose exercise training was effective to increase lumbar BMD but added WBV did not enhance this effect . However , falls were lowest in the exercise program combined with WBV . Introduction WBV is a new approach to reduce the risk of osteoporotic fractures . In the “ Erlangen Longitudinal Vibration Study ” ( ELVIS ) , we investigated whether WBV enhances the effect of multifunctional exercise on BMD and falls . Methods One hundred fifty-one postmenopausal women ( 68.5 ± 3.1 years ) were r and omly assigned to a : ( 1 ) conventional training group ( TG ) ; ( 2 ) conventional training group including vibration ( TGV ) ; and ( 3 ) wellness control group ( CG ) . TG conducted an exercise program consisting of 20 min dancing aerobics , 5 min balance training , 20 min functional gymnastics , and 15 min dynamic leg-strength training on vibration plates ( without vibration ) twice a week . TGV performed an identical exercise regimen with vibration ( 25–35 Hz ) during the leg-strengthening sequence . CG performed a low-intensity wellness program . BMD was measured at the hip and lumbar spine at baseline and follow-up using the DXA method . Falls were recorded daily via the calendar method . Results After 18 months , an increase in BMD at the lumbar spine was observed in both training groups ( TGV : + 1.5 % vs. TG : + 2.1 % ) . The difference between the TG and the CG ( 1.7 % ) was significant . At the hip no changes were determined in either group . The fall frequency was significantly lower in TGV ( 0.7 falls/person ) compared with CG ( 1.5 ) , whereas the difference between TG ( 0.96 ) and CG was not significant . Conclusions A multifunctional training program had a positive impact on lumbar BMD . The application of vibration did not enhance these effects . However , only the training including WBV affected the number of falls significantly UNLABELLED The potential for brief periods of low-magnitude , high-frequency mechanical signals to enhance the musculoskeletal system was evaluated in young women with low BMD . Twelve months of this noninvasive signal , induced as whole body vibration for at least 2 minutes each day , increased bone and muscle mass in the axial skeleton and lower extremities compared with controls . INTRODUCTION The incidence of osteoporosis , a disease that manifests in the elderly , may be reduced by increasing peak bone mass in the young . Preliminary data indicate that extremely low-level mechanical signals are anabolic to bone tissue , and their ability to enhance bone and muscle mass in young women was investigated in this study . MATERIAL S AND METHODS A 12-month trial was conducted in 48 young women ( 15 - 20 years ) with low BMD and a history of at least one skeletal fracture . One half of the subjects underwent brief ( 10 minutes requested ) , daily , low-level whole body vibration ( 30 Hz , 0.3 g ) ; the remaining women served as controls . Quantitative CT performed at baseline and at the end of study was used to establish changes in muscle and bone mass in the weight-bearing skeleton . RESULTS Using an intention-to-treat ( ITT ) analysis , cancellous bone in the lumbar vertebrae and cortical bone in the femoral midshaft of the experimental group increased by 2.1 % ( p = 0.025 ) and 3.4 % ( p < 0.001 ) , respectively , compared with 0.1 % ( p = 0.74 ) and 1.1 % ( p = 0.14 ) , in controls . Increases in cancellous and cortical bone were 2.0 % ( p = 0.06 ) and 2.3 % ( p = 0.04 ) greater , respectively , in the experimental group compared with controls . Cross-sectional area of paraspinous musculature was 4.9 % greater ( p = 0.002 ) in the experimental group versus controls . When a per protocol analysis was considered , gains in both muscle and bone were strongly correlated to a threshold in compliance , where the benefit of the mechanical intervention compared with controls was realized once subjects used the device for at least 2 minute/day ( n = 18 ) , as reflected by a 3.9 % increase in cancellous bone of the spine ( p = 0.007 ) , 2.9 % increase in cortical bone of the femur ( p = 0.009 ) , and 7.2 % increase in musculature of the spine ( p = 0.001 ) compared with controls and low compliers ( n = 30 ) . CONCLUSIONS Short bouts of extremely low-level mechanical signals , several orders of magnitude below that associated with vigorous exercise , increased bone and muscle mass in the weight-bearing skeleton of young adult females with low BMD . Should these musculoskeletal enhancements be preserved through adulthood , this intervention may prove to be a deterrent to osteoporosis in the elderly Background and Purpose : Vibration training is a relatively new exercise intervention . This study investigated the effects of vibration exercise on strength ( force-producing capacity ) and power in older adults who are healthy . Participants and Methods : Thirty participants ( mean age=73.7 years , SD=4.6 ) were r and omly assigned to a vibration exercise training ( VIB ) group or an exercise without vibration training ( EX ) group . The interventions consisted of 3 sessions per week for 8 weeks . Outcome measures included isokinetic flexor and extensor strength and power of the hip , knee , and ankle . Results : The VIB group significantly improved ankle plantar flexor strength and power compared with the EX group . However , there were no significant differences between the VIB and EX groups for knee flexor or extensor strength . Discussion and Conclusion : Vibration training contributed to an increase in plantar flexor strength and power . However , the strength gains for the knee and hip flexors and extensors for the VIB group and the EX group were comparable . Future vibration protocol s should explore different body positions to target muscles higher up on the leg UNLABELLED A 1-year prospect i ve , r and omized , double-blind , and placebo-controlled trial of 70 postmenopausal women demonstrated that brief periods ( < 20 minutes ) of a low-level ( 0.2 g , 30 Hz ) vibration applied during quiet st and ing can effectively inhibit bone loss in the spine and femur , with efficacy increasing significantly with greater compliance , particularly in those subjects with lower body mass . INTRODUCTION Indicative of the anabolic potential of mechanical stimuli , animal models have demonstrated that short periods ( < 30 minutes ) of low-magnitude vibration ( < 0.3 g ) , applied at a relatively high frequency ( 20 - 90 Hz ) , will increase the number and width of trabeculae , as well as enhance stiffness and strength of cancellous bone . Here , a 1-year prospect i ve , r and omized , double-blind , and placebo-controlled clinical trial in 70 women , 3 - 8 years past the menopause , examined the ability of such high-frequency , low-magnitude mechanical signals to inhibit bone loss in the human . MATERIAL S AND METHODS Each day , one-half of the subjects were exposed to short- duration ( two 10-minute treatments/day ) , low-magnitude ( 2.0 m/s2 peak to peak ) , 30-Hz vertical accelerations ( vibration ) , whereas the other half stood for the same duration on placebo devices . DXA was used to measure BMD at the spine , hip , and distal radius at baseline , and 3 , 6 , and 12 months . Fifty-six women completed the 1-year treatment . RESULTS AND CONCLUSIONS The detection threshold of the study design failed to show any changes in bone density using an intention-to-treat analysis for either the placebo or treatment group . Regression analysis on the a priori study group demonstrated a significant effect of compliance on efficacy of the intervention , particularly at the lumbar spine ( p = 0.004 ) . Posthoc testing was used to assist in identifying various subgroups that may have benefited from this treatment modality . Evaluating those in the highest quartile of compliance ( 86 % compliant ) , placebo subjects lost 2.13 % in the femoral neck over 1 year , whereas treatment was associated with a gain of 0.04 % , reflecting a 2.17 % relative benefit of treatment ( p = 0.06 ) . In the spine , the 1.6 % decrease observed over 1 year in the placebo group was reduced to a 0.10 % loss in the active group , indicating a 1.5 % relative benefit of treatment ( p = 0.09 ) . Considering the interdependence of weight , the spine of lighter women ( < 65 kg ) , who were in the highest quartile of compliance , exhibited a relative benefit of active treatment of 3.35 % greater BMD over 1 year ( p = 0.009 ) ; for the mean compliance group , a 2.73 % relative benefit in BMD was found ( p = 0.02 ) . These preliminary results indicate the potential for a noninvasive , mechanically mediated intervention for osteoporosis . This non-pharmacologic approach represents a physiologically based means of inhibiting the decline in BMD that follows menopause , perhaps most effectively in the spine of lighter women who are in the greatest need of intervention We examined whether the effect of multi purpose exercise can be enhanced by whole-body vibration ( WBV ) . One hundred and fifty-one post-menopausal women ( 68.5 ± 3.1 years ) were r and omly assigned to three groups : ( 1 ) a training group ( TG ) ; ( 2 ) training including vibration ( VTG ) ; and ( 3 ) a wellness control group ( CG ) . TG and VTG performed the same training program twice weekly ( 60 min ) , consisting of aerobic and strength exercises , with the only difference that leg strength exercises ( 15 min ) were performed with ( VTG ) or without ( TG ) vibration . CG performed a low-intensity " wellness " program . At baseline and after 18 months , body composition was determined using dual-X-ray-absorptiometry . Maximum isometric strength was determined for the legs and the trunk region . Leg power was measured by countermovement jumps using a force-measuring plate . In the TG lean body mass , total body fat , and abdominal fat were favorably affected , but no additive effects were generated by the vibration stimulus . However , concerning muscle strength and power , there was a tendency in favor of the VTG . Only vibration training result ed in a significant increase of leg and trunk flexion strength compared with CG . In summary , WBV embedded in a multi purpose exercise program showed minor additive effects on body composition and neuromuscular performance |
2,218 | 23,451,939 | Whatever the clinical context , few health-care providers consistently attempt to facilitate patient involvement , and even fewer adjust care to patient preferences .
However , both SDM interventions and longer consultations could improve this | BACKGROUND We have no clear overview of the extent to which health-care providers involve patients in the decision-making process during consultations .
The Observing Patient Involvement in Decision Making instrument ( OPTION ) was design ed to assess this .
OBJECTIVE To systematic ally review studies that used the OPTION instrument to observe the extent to which health-care providers involve patients in decision making across a range of clinical context s , including different health professions and lengths of consultation . | BACKGROUND Important barriers to the wider implementation of shared decision making ( SDM ) and risk communication in practice remain . The attitudes of professionals undergoing training in these approaches may inform how to overcome these barriers , but there are few such data yet available . AIM To identify the attitudes of professionals during participation in a large practice -based intervention study with substantial individual exposure to SDM and risk communication , and to assess their confidence with these approaches and reported frequency of implementing them . SETTING AND PARTICIPANTS Twenty general practitioners ( GPs ) who had been in practice between 1 and 10 years , and participated in an explanatory trial lasting 6 months . The trial interventions comprised training in SDM skills and the use of risk communication material s. The doctors consulted with up to 48 patients each ( mean = 40 , half of them audio-taped ) for the study . METHODS Question naire assessment s before and after each training stage . RESULTS The GPs indicated positive attitudes towards involving patients and towards the training interventions . They indicated that the risk information packs were applicable but had used them only occasionally with patients outside the trial . No statistically significant changes were associated with the specific interventions in terms of doctors ' confidence in discussing risk information after the risk communication intervention , or attitudes to patient involvement after the SDM intervention . Most attitudes and confidence ratings showed positive changes during the course of the trial as a cohort effect . Such positive changes were associated with female doctors more than male doctors , but not with MRCGP ( postgraduate vocational ) qualification . Time constraints remained important throughout the study in not implementing the approach more frequently . CONCLUSIONS Professionals appear receptive to patient involvement , and willing to acquire the relevant skills . SDM and risk communication training did not appear to contribute differentially to this . Practical barriers such as time constraints should probably be addressed with greater priority than the precise content of training or continuing professional development initiatives if ' involvement ' is to become a commoner experience for patients in primary care Background — Cardiac stress testing in patients at low risk for acute coronary syndrome is associated with increased false-positive test results , unnecessary downstream procedures , and increased cost . We judged it unlikely that patient preferences were driving the decision to obtain stress testing . Methods and Results — The Chest Pain Choice trial was a prospect i ve r and omized evaluation involving 204 patients who were r and omized to a decision aid or usual care and were followed for 30 days . The decision aid included a 100-person pictograph depicting the pretest probability of acute coronary syndrome and available management options ( observation unit admission and stress testing or 24–72 hours outpatient follow-up ) . The primary outcome was patient knowledge measured by an immediate postvisit survey . Additional outcomes included patient engagement in decision making and the proportion of patients who decided to undergo observation unit admission and cardiac stress testing . Compared with usual care patients ( n=103 ) , decision aid patients ( n=101 ) had significantly greater knowledge ( 3.6 versus 3.0 questions correct ; mean difference , 0.67 ; 95 % CI , 0.34–1.0 ) , were more engaged in decision making as indicated by higher OPTION ( observing patient involvement ) scores ( 26.6 versus 7.0 ; mean difference , 19.6 ; 95 % CI , 1.6–21.6 ) , and decided less frequently to be admitted to the observation unit for stress testing ( 58 % versus 77 % ; absolute difference , 19 % ; 95 % CI , 6%–31 % ) . There were no major adverse cardiac events after discharge in either group . Conclusions — Use of a decision aid in patients with chest pain increased knowledge and engagement in decision making and decreased the rate of observation unit admission for stress testing . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01077037 OBJECTIVE To test the effect of three questions ( what are my options ? what are the benefits and harms ? and how likely are these ? ) , on information provided by physicians about treatment options . METHODS We used a cross-over trial using two unannounced st and ardized patients ( SPs ) simulating a presentation of mild-moderate depression . One SP was assigned the intervention role ( asking the questions ) , the other the control role . An intervention and control SP visited each physician , order allocated r and omly . The study was conducted in family practice s in Sydney , Australia , during 2008 - 09 . Data were obtained from consultation audio-recordings . Information about treatment options and patient involvement were analyzed using the Assessing Communication about Evidence and Patient Preferences ( ACEPP ) tool and the OPTION tool . RESULTS Thirty-six SP visits were completed ( 18 intervention , 18 control ) . Scores were higher in intervention consultations than controls : ACEPP scores 21.4 vs. 16.6 , p<0.001 , difference 4.7 ( 95 % CI 2.3 - 7.0 ) and OPTION scores 36 vs. 25 , p=0.001 , difference 11.5 ( 95 % CI 5.1 - 17.8 ) , indicating greater information provision and behavior supporting patient involvement . CONCLUSION Asking these three questions improved information given by family physicians and increased physician facilitation of patient involvement . Practice implication s. These questions can drive evidence -based practice , strengthen patient-physician communication , and improve safety and quality BACKGROUND Patient involvement in the decision-making process is a key element for good clinical practice . Few data are available on patient involvement in psychiatry . AIMS To assess in a psychiatric out-patient context how psychiatrists involve patients in therapeutic decisions and to determine the extent to which patient and psychiatrist characteristics contribute to patient involvement . METHOD Eighty transcripts from audiotaped first out-patient consultations , conducted by 16 psychiatrists , were rated with the OPTION ( observing patient involvement ) scale . Interrater reliability indices were obtained for 30 r and omly selected interviews . Associations between OPTION scores and some clinical and socio-demographic variables were tested using t-test , ANOVA and Pearson 's correlation coefficient where appropriate . The distribution of scores for each psychiatrist was assessed by intracluster correlation coefficients . RESULTS Interrater reliability and internal consistency of the OPTION scale in the psychiatric setting were satisfactory . The total score and the ratings for the single OPTION items showed a skewed distribution , with a prevalence of scores in the low range of abilities , corresponding to minimal attempts to involve patients or a minimal skill level . CONCLUSIONS The OPTION scale proves to be a reliable instrument to assess patient involvement in a psychiatric setting . Psychiatrists showed poor patient involvement abilities parallel to previous findings in psychiatry and primary care . They need to be encouraged to share treatment decisions with their patients and to apply patient involvement skills . Further research is needed to establish which patient variables and clinical setting s in psychiatry are more amenable to shared decisions , and how participation of psychiatric patients in treatment decisions will affect the outcome BACKGROUND Poor quality of information transfer about the benefits and risks of statin drug use may result in patients not making informed decisions that they can act on in a timely fashion . METHODS The effect of a decision aid about statin drugs on treatment decision making in 98 patients with diabetes was determined in a cluster r and omized trial of decision aid vs control pamphlet , with concealed allocation , blinding of participants to study goals , and adherence to the intention-to-treat principle . Twenty-one endocrinologists conducted specialty outpatient metabolic consultations . Patients in the intervention group received Statin Choice , a tailored decision aid that presents the estimated 10-year cardiovascular risk , the absolute risk reduction with use of statin drugs , and the disadvantages of using statin drugs . Patients in the control group received the institution 's pamphlet about cholesterol management . We measured acceptability , knowledge about options and cardiovascular risk , and decisional conflict immediately after the visit , and adherence to pill taking was measured 3 months later . RESULTS Patients favored using the decision aid ( odds ratio [ OR ] , 2.8 ; 95 % confidence interval [ CI ] , 1.2 - 6.9 ) ; patients who received the decision aid ( n = 52 ) knew more ( difference , 2.4 of 9 points ; 95 % CI , 1.5 - 3.3 ) , had better estimated cardiovascular risk ( OR , 22.4 ; 95 % CI , 5.9 - 85.6 ) and potential absolute risk reduction with statin drugs ( OR , 6.7 ; 95 % CI , 2.2 - 19.7 ) , and had less decisional conflict ( difference , -10.6 ; 95 % CI , -15.4 to -5.9 on a 100-point scale ) than did patients in the control group ( n = 46 ) . Of 33 patients in the intervention group taking statin drugs at 3 months , 2 reported missing 1 dose or more in the last week compared with 6 of 29 patients in the control group taking statin drugs ( OR , 3.4 ; 95 % CI , 1.5 - 7.5 ) . CONCLUSIONS A decision aid enhanced decision making about statin drugs and may have favorably affected drug adherence BACKGROUND Patient involvement in the choice of antihyperglycemic agents could improve adherence and optimize glycemic control in patients with type 2 diabetes mellitus . METHODS We conducted a pilot , cluster r and omized trial of Diabetes Medication Choice , a decision aid that describes 5 antihyperglycemic drugs , their treatment burden ( adverse effects , administration , and self-monitoring dem and s ) , and impact on hemoglobin A(1c ) ( HbA(1c ) ) levels . Twenty-one clinicians were r and omized to use the decision aid during the clinical encounter and 19 to dispense usual care and an educational pamphlet . We used surveys and video analysis to assess postvisit decisional outcomes , and medical and pharmacy records to assess 6-month medication adherence and HbA(1c ) levels . RESULTS Compared with usual care patients ( n = 37 ) , patients receiving the decision aid ( n = 48 ) found the tool more helpful ( clustered-adjusted mean difference [ AMD ] in a 7-point scale , 0.38 ; 95 % confidence interval [ CI ] , 0.04 - 0.72 ) ; had improved knowledge ( AMD , 1.10 of 10 questions ; 95 % CI , 0.11 - 2.09 ) ; and had more involvement in making decisions about diabetes medications ( AMD , 21.8 of 100 ; 95 % CI , 13.0 - 30.5 ) . At 6-month follow-up , both groups had nearly perfect medication use ( median , 100 % of days covered ) , with better adherence ( AMD , 9 % more days covered ; 95 % CI , 4%-14 % ) and persistence ( AMD , 12 more days covered ; 95 % CI , 3 - 21 days ) in the usual care group , and no significant impact on HbA(1c ) levels ( AMD , 0.01 ; 95 % CI , -0.49 to 0.50 ) . CONCLUSION An innovative decision aid effectively involved patients with type 2 diabetes mellitus in decisions about their medications but did not improve adherence or HbA(1c ) levels . Trial Registration clinical trials.gov Identifier : NCT00388050 OBJECTIVE Poor adherence to therapy , perhaps related to unaddressed patient preferences , limits the effectiveness of osteoporosis treatment in at-risk women . A parallel patient-level r and omized trial in primary care practice s was performed . METHODS Eligible postmenopausal women with bone mineral density T-scores less than -1.0 and not receiving bisphosphonate therapy were included . In addition to usual primary care , intervention patients received a decision aid ( a tailored pictographic 10-year fracture risk estimate , absolute risk reduction with bisphosphonates , side effects , and out-of-pocket cost ) , and control patients received a st and ard brochure . Knowledge transfer , patient involvement in decision-making , and rates of bisphosphonate start and adherence were studied . Data came from medical records , post-visit written and 6-month phone surveys , video recordings of clinical encounters , and pharmacy prescription profiles . RESULTS A total of 100 patients ( range of 10-year fracture risk , 6%-60 % ) were allocated r and omly to receive the decision aid ( n=52 ) or usual care ( n=48 ) . Patients receiving the decision aid were 1.8 times more likely to correctly identify their 10-year fracture risk ( 49 % vs 28 % ; 95 % confidence interval [ CI ] , 1.03 - 3.2 ) and 2.7 times more likely to identify their estimated risk reduction with bisphosphonates ( 43 % vs 16 % ; 95 % CI , 1.3 - 5.7 ) . Patient involvement improved with the decision aid by 23 % ( 95 % CI , 13.6 - 31.4 ) . Bisphosphonates were started by 44 % of patients receiving the decision aid and 40 % of patients receiving usual care . Adherence at 6 months was similarly high across both groups , but the proportion with more than 80 % adherence was higher with the decision aid ( n=23 [ 100 % ] vs n=14 [ 74 % ] ; P = .009 ) . CONCLUSION A decision aid improved the quality of clinical decisions about bisphosphonate therapy in at-risk postmenopausal women , did not affect start rates , and may have improved adherence BACKGROUND A consulting method known as ' shared decision making ' ( SDM ) has been described and operationalized in terms of several ' competences ' . One of these competences concerns the discussion of the risks and benefits of treatment or care options-'risk communication ' . Few data exist on clinicians ' ability to acquire skills and implement the competences of SDM or risk communication in consultations with patients . OBJECTIVE The aims of this study were to evaluate the effects of skill development workshops for SDM and the use of risk communication aids on the process of consultations . METHODS A cluster r and omized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practice s in Gwent , South Wales . A total of 747 patients with known atrial fibrillation , prostatism , menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments . Half the consultations were r and omly selected for audio-taping , of which 352 patients attended and were audio-taped successfully . After baseline , participating doctors were r and omized to receive training in ( i ) SDM skills or ( ii ) the use of simple risk communication aids , using simulated patients . The alternative training was then provided for the final study phase . Patients were allocated r and omly to a consultation during baseline or intervention 1 ( SDM or risk communication aids ) or intervention 2 phases . A r and omly selected half of the consultations were audio-taped from each phase . Raters ( independent , trained and blinded to study phase ) assessed the audio-tapes using a vali date d scale to assess levels of patient involvement ( OPTION : observing patient involvement ) , and to analyse the nature of risk information discussed . Clinicians completed question naires after each consultation , assessing perceived clinician-patient agreement and level of patient involvement in decisions . Multilevel modelling was carried out with the OPTION score as the dependent variable , and rater , consultation and clinician levels of data , st and ardized by rater within clinician . RESULTS Following each of the interventions , the clinicians significantly increased their involvement of patients in decision making ( OPTION score increased by 10.6 following risk communication training [ 95 % confidence interval ( CI ) 7.9 -13.3 ; P < 0.001 ] and by 12.9 after SDM skill development ( 95 % CI 10 -15.8 , P < 0.001 ) , a moderate effect size . The level of involvement achieved by the risk communication aids was significantly increased by the subsequent introduction of the skill development workshops ( 7.7 increase in OPTION score , 95 % CI 3.4 - 12 ; P < 0.001 ) . The alternative sequence ( skills followed by risk communication aids ) did not achieve this effect . The use of most risk information formats increased after the provision of specific risk communication aids ( P < 0.001 ) . Clinicians using the risk communication tools perceived significantly higher patient and clinician agreement on treatment ( P < 0.001 ) , patient satisfaction with information ( P < 0.01 ) , clinician satisfaction with decision ( P < 0.01 ) and general overall satisfaction with the consultation ( P < 0.001 ) than those who were exposed to SDM skill development workshops . CONCLUSIONS These clinicians were able to acquire the skills to implement SDM competences and to use risk communication aids . Each intervention provided independent effects . Further progress towards greater patient involvement in health care decision making is possible , and skill development in this area should be incorporated into postgraduate professional development programmes Background Chest pain is a common presenting complaint in the emergency department ( ED ) . Despite the frequency with which clinicians evaluate patients with chest pain , accurately determining the risk of acute coronary syndrome ( ACS ) and sharing risk information with patients is challenging . The aims of this study are ( 1 ) to develop a decision aid ( CHEST PAIN CHOICE ) that communicates the short-term risk of ACS and ( 2 ) to evaluate the impact of the decision aid on patient participation in decision-making and re source use . Methods / Design This is a protocol for a parallel , 2-arm r and omized trial to compare an intervention group receiving CHEST PAIN CHOICE to a control group receiving usual ED care . Adults presenting to the Saint Mary 's Hospital ED in Rochester , MN USA with a primary complaint of chest pain who are being considered for admission for prolonged ED observation in a specialized unit and urgent cardiac stress testing will be eligible for enrollment . We will measure the effect of CHEST PAIN CHOICE on six outcomes : ( 1 ) patient knowledge regarding their short-term risk for ACS and the risks of radiation exposure ; ( 2 ) quality of the decision making process ; ( 3 ) patient and clinician acceptability and satisfaction with the decision aid ; ( 4 ) the proportion of patients who decided to undergo observation unit admission and urgent cardiac stress testing ; ( 5 ) economic costs and healthcare utilization ; and ( 6 ) the rate of delayed or missed ACS . To capture these outcomes , we will administer patient and clinician surveys after each visit , obtain video recordings of the clinical encounters , and conduct 30-day phone follow-up . Discussion This pilot r and omized trial will develop and evaluate a decision aid for use in ED chest pain patients at low risk for ACS and provide a preliminary estimate of its effect on patient participation in decision-making and re source use . Trial registration Clinical Trials.gov Identifier : Objective Patient involvement into medical decisions as conceived in the shared decision making method ( SDM ) is essential in evidence based medicine . However , it is not conclusively evident how best to define , realize and evaluate involvement to enable patients making informed choices . We aim ed at investigating the ability of four measures to indicate patient involvement . While use and reporting of these instruments might imply wide overlap regarding the addressed constructs this assumption seems question able with respect to the diversity of the perspectives from which the assessment s are administered . Methods The study investigated a nested cohort ( N = 79 ) of a r and omized trial evaluating a patient decision aid on immunotherapy for multiple sclerosis . Convergent validities were calculated between observer ratings of videotaped physician-patient consultations ( OPTION ) and patients ' perceptions of the communication ( Shared Decision Making Question naire , Control Preference Scale & Decisional Conflict Scale ) . Results OPTION reliability was high to excellent . Communication performance was low according to OPTION and high according to the three patient administered measures . No correlations were found between observer and patient judges , neither for means nor for single items . Patient report measures showed some moderate correlations . Conclusion Existing SDM measures do not refer to a single construct . A gold st and ard is missing to decide whether any of these measures has the potential to indicate patient involvement . Practice Implication s Pronounced heterogeneity of the underpinning constructs implies difficulties regarding the interpretation of existing evidence on the efficacy of SDM . Consideration of communication theory and basic definitions of SDM would recommend an inter-subjective focus of measurement . Trial Registration Controlled-Trials.com IS RCT N25267500 BACKGROUND Shared Decision Making ( SDM ) is widely accepted as the preferred method for reaching treatment decisions in the oncology setting including those about clinical trial participation : however , there is some disagreement between research ers over the components of SDM . Specific st and ardized coding systems are needed to help overcome this difficulty . OBJECTIVE The first objective was to describe the development of an oncology specific SDM coding system , the DAS-O. The second objective was to provide reliability and validity data supporting the DAS-O. SETTING AND PARTICIPANTS Consultation data were available from tertiary cancer center out patient oncology clinics in : Australia , New Zeal and ( ANZ ) , Switzerl and , Germany and Austria ( SGA ) . Patients were women with a confirmed diagnosis of early stage breast cancer . Reliability data were from 18 r and omly selected coded transcripts drawn from ANZ and SGA . Concurrent validity data are from 55 ( ANZ ) consultations . MEASUREMENT Inter and Intra rater reliability data was evaluated using Kappa correlation statistics and correlation coefficients . Correlation coefficients were used to assess concurrent validity between the DAS-O and two other SDM coding systems , OPTION and DSAT . RESULTS Inter and Intra rater reliability for the system were high with average Kappas of 0.58 and 0.65 respectively . Correlation coefficients between DAS-O and OPTION was 0.73 and > 0.5 for DSAT . CONCLUSIONS We have developed a reliable and valid coding system for identifying and rating the quality of SDM in breast cancer consultations BACKGROUND Although shared decision making ( SDM ) has been reported to facilitate quality care , few studies have explored the extent to which SDM is implemented in primary care and factors that influence its application . This study assesses the extent to which physicians enact SDM behaviors and describes factors associated with physicians ' SDM behaviors within the context of depression care . METHODS In a secondary analysis of data from a r and omized experiment , we coded 287 audiorecorded interactions between physicians and st and ardized patients ( SPs ) using the Observing Patient Involvement ( OPTION ) system to assess physician SDM behaviors . We performed a series of generalized linear mixed model analyses to examine physician and patient characteristics associated with SDM behavior . RESULTS The mean ( SD ) OPTION score was 11.4 ( 3.3 ) of 48 possible points . Older physicians ( partial correlation coefficient = -0.29 ; beta = -0.09 ; P < .01 ) and physicians who practice d in a health maintenance organization setting ( beta = -1.60 ; P < .01 ) performed fewer SDM behaviors . Longer visit duration was associated with more SDM behaviors ( partial correlation coefficient = 0.31 ; beta = 0.08 ; P < .01 ) . In addition , physicians enacted more SDM behaviors with SPs who made general ( beta = 2.46 ; P < .01 ) and br and -specific ( beta = 2.21 ; P < .01 ) medication requests compared with those who made no request . CONCLUSIONS In the context of new visits for depressive symptoms , primary care physicians performed few SDM behaviors . However , physician SDM behaviors are influenced by practice setting and patient-initiated requests for medication . Additional research is needed to identify interventions that encourage SDM when indicated As patients become more involved in decisions affecting their health , it is important to monitor and improve the support clinicians provide to facilitate shared decision making . The Decision Support Analysis Tool ( DSAT ) was developed as a research tool to evaluate practitioners ' use of decision support and related communication skills during a clinical encounter . The DSAT , consisting of six categories of decision support skills and four categories of communication skills , was tested with 34 actual transcripts of patient-physician dialogue . The patients were prepared for the clinical encounter with either a detailed decision aid plus worksheet ( n=16 ) or a pamphlet ( n=18 ) . Pairs of raters , blinded to the intervention allocation , coded each transcript independently . The overall inter-rater agreement and kappa coefficients were , respectively 75 % and 0.59 for the decision support skills and 76 % and 0.68 for the communication skills categories . The frequency of DSAT skills coded : ( a ) were significantly correlated with three out of six patient and physician outcome measures ( r>0.30 , P<0.05 ) ; and ( b ) showed significant discrimination ( P=0.05 ) or trends ( P<0.15 ) in discrimination between the decision aid and pamphlet groups . The DSAT shows promise as a reliable and valid evaluation tool but requires further testing with larger sample OBJECTIVES To describe the amount of shared decision-making ( SDM ) behavior exhibited during treatment-planning encounters for children newly diagnosed as having attention-deficit/hyperactivity disorder and to explore relationships between participant characteristics and the amount of SDM . DESIGN Prospect i ve cohort study . SETTING Seven community-based primary care pediatric practice s in the Cincinnati , Ohio ; northern Kentucky ; and southeast Indiana regions from October 5 , 2009 , through August 9 , 2010 . PARTICIPANTS Ten pediatricians and 26 families with a 6- to 10-year-old child newly diagnosed as having attention-deficit/hyperactivity disorder . OUTCOME MEASURE The amount of SDM behavior exhibited during videorecorded encounters , as coded by 2 independent raters using the vali date d Observing Patient Involvement ( OPTION ) scale , which was adapted for use in pediatric setting s and produces a score ranging from 0 ( no parental involvement ) to 100 ( maximal parental involvement ) . RESULTS Treatment decisions focused on initiation of medication treatment . The mean ( SD ) total OPTION score was 28.5 ( 11.7 ) . More SDM was observed during encounters involving families with white vs nonwhite children ( adjusted mean difference score , 14.9 ; 95 % confidence interval [ CI ] , 10.2 - 19.6 ; P < .001 ) , private vs public health insurance coverage ( adjusted mean difference score , 15.1 ; 11.2 - 19.0 ; P < .001 ) , mothers with at least some college education vs high school graduate or less ( adjusted mean difference score , 12.3 ; 7.2 - 17.4 ; P < .001 ) , and parents who did not screen positive for serious mental illness vs those who did ( adjusted mean difference score , 15.0 ; 11.9 - 18.1 ; P < .001 ) . CONCLUSIONS Low levels of SDM were observed . Exploratory analyses identified potential disparities and barriers . Interventions may be needed to foster SDM with all parents , especially those of nonwhite race , of lower socioeconomic status , of lower educational level , and with serious mental illness |
2,219 | 30,345,166 | Patient-centered interventions that provided patient information effectively increased the appropriate use of BZDs .
The educational approaches for HCPs that aim ed to achieve appropriate prescription reported inconsistent results .
The methods that combined informing patients and HCPs led to a significant reduction in BZD use .
Conclusions This is the first review of studies focused on patient-centered approaches to reducing the inappropriate prescription and use of BZDs and z-drugs .
The patient-centered dimension of patient information was responsible for a decrease in BZD and z-drug consumption .
Further , in some studies , the patient-centered dimensions responsible for reducing the prescription and use of BZDs and z-drugs were the clinician 's essential characteristics and clinician-patient communication | Background Benzodiazepines ( BZDs ) and z-drugs are effective drugs , but they are prescribed excessively worldwide .
International guidelines recommend a maximum treatment duration of 4 weeks .
Although these drugs are effective in the short-term , long-term BZD therapy is associated with considerable adverse effects , the development of tolerance and , finally , addiction .
However , there are different interventions in terms of patient-centered care that aim to reduce the use of BZDs and z-drugs as well as assist health care professionals ( HCPs ) in preventing the inappropriate prescription of BZDs .
Aim The aim of this systematic review was to identify interventions that promote patient-centered treatments for inappropriate BZD and z-drug use and to analyze their effectiveness in reducing the inappropriate use of these drugs . | BACKGROUND Benzodiazepines are extensively used in primary care , but their long-term use is associated with adverse health outcomes and dependence . AIMS To analyse the efficacy of two structured interventions in primary care to enable patients to discontinue long-term benzodiazepine use . METHOD A multicentre three-arm cluster r and omised controlled trial was conducted , with r and omisation at general practitioner level ( trial registration IS RCT N13024375 ) . A total of 532 patients taking benzodiazepines for at least 6 months participated . After all patients were included , general practitioners were r and omly allocated ( 1:1:1 ) to usual care , a structured intervention with follow-up visits ( SIF ) or a structured intervention with written instructions ( SIW ) . The primary end-point was the last month self-declared benzodiazepine discontinuation confirmed by prescription cl aims at 12 months . RESULTS At 12 months , 76 of 168 ( 45 % ) patients in the SIW group and 86 of 191 ( 45 % ) in the SIF group had discontinued benzodiazepine use compared with 26 of 173 ( 15 % ) in the control group . After adjusting by cluster , the relative risks for benzodiazepine discontinuation were 3.01 ( 95 % CI 2.03 - 4.46 , P<0.0001 ) in the SIW and 3.00 ( 95 % CI 2.04 - 4.40 , P<0.0001 ) in the SIF group . The most frequently reported withdrawal symptoms were insomnia , anxiety and irritability . CONCLUSIONS Both interventions led to significant reductions in long-term benzodiazepine use in patients without severe comorbidity . A structured intervention with a written individualised stepped-dose reduction is less time-consuming and as effective in primary care as a more complex intervention involving follow-up visits This study examined the potential for cognitive morbidity associated with the long-term use of benzodiazepine ( BZ ) sedative-hypnotics in a sample of healthy older adults . Tests of memory , attention and processing speed were conducted prior to and 1 month after drug discontinuation for 25 BZ-users and at similar intervals for 26 healthy control subjects . After controlling for differences in affective status between BZ-users and controls , there were no significant group differences in cognitive performance . However , BZ-users showed greater gains on tests of attention and speed of processing at repeat testing compared with controls this improvement was not attributable to a change in affective status . These findings suggest that there may be subtle and reversible effects of long-term BZ use on speed-dependent tasks in older adults . However , the magnitude of these effects is quite small and may be of little clinical significance in the healthy elderly BACKGROUND Benzodiazepine use by elderly patients is associated with adverse outcomes including increased risk of falls and fractures , motor vehicle accidents and cognitive impairment . Recent studies suggest that individualized feedback and education to physicians may improve drug prescribing . In this study , we evaluated an intervention to address the inappropriate prescribing of benzodiazepines for elderly patients . METHODS We identified 1624 primary care physicians who wrote at least 10 prescriptions for the target drugs in a 2-month period and r and omly assigned these physicians to the intervention group or the control group . We obtained data from the Ontario Drug Benefit cl aims data base , which covers all Ontario residents aged 65 years and over for drugs selected from a minimally restrictive formulary . Every 2 months for 6 months , confidential profiles of benzodiazepine prescription use coupled with evidence -based educational bulletins were mailed to the intervention group . The control group received feedback and educational bulletins about first-line antihypertension drug prescribing for elderly patients . Our main outcome measures were reductions in the proportion of each physician 's total benzodiazepine prescriptions for long-acting agents , combinations of benzodiazepines with other psychoactive medications ( including other benzodiazepines ) and long-term benzodiazepine therapy . RESULTS After r and omization , 168 physicians agreed to be in the intervention group and 206 in the control group . Their demographic and prescribing characteristics were similar . Although the proportion of long-acting benzodiazepine prescriptions decreased by 0.7 % in the intervention group between the baseline period and the end of the intervention period ( from 20.3 % , or a mean of 29.5 prescriptions , to 19.6 % , or a mean of 27.7 prescriptions ) and increased by 1.1 % in the control group ( from 19.8 % , or a mean of 26.4 prescriptions , to 20.9 % , or a mean of 27.7 prescriptions ) ( p = 0.036 ) , this difference was not clinical ly significant . There was no significant difference over the study period in either combination prescribing of benzodiazepines or in prescriptions for long-term benzodiazepine therapy . INTERPRETATION We did not find that a program of confidential feedback and educational material offered to Ontario primary care physicians had a clinical ly significant impact on their benzodiazepine prescribing AIMS Chronic benzodiazepine use is highly prevalent and is associated with a variety of negative health consequences . The present study examined the long-term effectiveness of a tailored patient education intervention on benzodiazepine use . DESIGN A r and omized controlled trial was conducted comprising three arms , comparing ( i ) a single tailored intervention ; ( ii ) a multiple tailored intervention and ( iii ) a general practitioner letter . The post-test took place after 12 months . PARTICIPANTS Five hundred and eight patients using benzodiazepines were recruited by their general practitioners and assigned r and omly to one of the three groups . INTERVENTION Two tailored interventions , the single tailored intervention ( patients received one tailored letter ) and the multiple tailored intervention ( patients received three sequential tailored letters at intervals of 1 month ) , were compared to a short general practitioner letter that modelled usual care . The tailored interventions not only provided different and more information than the general practitioner letter ; they were also personalized and adapted to individual baseline characteristics . The information in both tailored interventions was the same , but in the multiple tailored intervention the information was provided to the participants spread over three occasions . In the multiple tailored intervention , the second and the third tailored letters were based on short and st and ardized telephone interviews . MEASUREMENTS Benzodiazepine cessation at post-test was the outcome measure . FINDINGS The results showed that participants receiving the tailored interventions were twice as likely to have quit benzodiazepine use compared to the general practitioner letter . Particularly among participants with the intention to discontinue usage at baseline , both tailored interventions led to high percentages of those who actually discontinued usage ( single tailored intervention 51.7 % ; multiple tailored intervention 35.6 % ; general practitioner letter 14.5 % ) . CONCLUSIONS It was concluded that tailored patient education can be an effective tool for reducing benzodiazepine use , and can be implemented easily 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 About two-thirds of long-term users of benzodiazepines in the population are able to discontinue this drug with the aid of supervised programmes for tapering off . Little is known about the long-term outcome of such programmes , and they have never been compared with usual care . After a 15-month follow-up of a r and omised controlled trial comparing such a programme with and without psychotherapy with usual care , we found significantly higher longitudinal abstinence rates in long-term benzodiazepine users who received a benzodiazepine tapering-off programme without psychotherapy ( 25 out of 69 , 36 % ) compared with those who received usual care ( 5 out of 33,15 % ; P=0.03 ) OBJECTIVES To test the effect of an adapted U.S. model of pharmaceutical care on prescribing of inappropriate psychoactive ( anxiolytic , hypnotic , and antipsychotic ) medications and falls in nursing homes for older people in Northern Irel and ( NI ) . DESIGN Cluster r and omized controlled trial . SETTING Nursing homes r and omized to intervention ( receipt of the adapted model of care ; n=11 ) or control ( usual care continued ; n=11 ) . PARTICIPANTS Residents aged 65 and older who provided informed consent ( N=334 ; 173 intervention , 161 control ) . INTERVENTION Specially trained pharmacists visited intervention homes monthly for 12 months and review ed residents ' clinical and prescribing information , applied an algorithm that guided them in assessing the appropriateness of psychoactive medication , and worked with prescribers ( general practitioners ) to improve the prescribing of these drugs . The control homes received usual care . MEASUREMENTS The primary end point was the proportion of residents prescribed one or more inappropriate psychoactive medicine according to st and ardized protocol s ; falls were evaluated using routinely collected falls data m and ated by the regulatory body for nursing homes in NI . RESULTS The proportion of residents taking inappropriate psychoactive medications at 12 months in the intervention homes ( 25/128 , 19.5 % ) was much lower than in the control homes ( 62/124 , 50.0 % ) ( odds ratio=0.26 , 95 % confidence interval=0.14 - 0.49 ) after adjustment for clustering within homes . No differences were observed at 12 months in the falls rate between the intervention and control groups . CONCLUSION Marked reductions in inappropriate psychoactive medication prescribing in residents result ed from pharmacist review of targeted medications , but there was no effect on falls OBJECTIVE To investigate the effectiveness of an educational Quality Use of Medicines program , delivered at the level of general practice , on medicines use , falls and quality of life in people aged > or = 65 years . DESIGN Cluster r and omised controlled trial conducted in 2002 . SETTING General practice s in the Hunter Region , New South Wales , Australia . PARTICIPANTS Twenty general practitioners recruited 849 patients to participate in the study . INTERVENTION Education ( academic detailing , provision of prescribing information and feedback ) ; medication risk assessment ; facilitation of medication review ; financial incentives . MAIN OUTCOME MEASURES PRIMARY MEASURES a composite score reflecting use of benzodiazepines , non-steroidal anti-inflammatory drugs ( NSAIDs ) and thiazide diuretics ; secondary measures : use of medication review s , occurrence of falls , quality of life ( as assessed by SF-12 and EQ-5D survey scores . RESULTS Compared with the control group , participants in the intervention group had increased odds of having an improved medication use composite score ( odds ratio [ OR ] , 1.86 ; 95 % CI , 1.21 - 2.85 ) at 4-month follow-up but not at 12 months . At 4-month follow-up , the intervention group had reduced odds of using NSAIDs ( OR , 0.62 ; 95 % CI , 0.39 - 0.99 ) and showed a non-significant reduction in use of benzodiazepines ( OR , 0.51 ; 95 % CI , 0.20 - 1.30 ) and thiazide diuretics ( OR , 0.70 ; 95 % CI , 0.48 - 1.01 ) . Changes in drug use were not significant at 12-month follow-up . At 12 months , intervention-group participants had lower adjusted ORs ( AORs ) for having a fall ( AOR , 0.61 ; 95 % CI , 0.41 - 0.91 ) , injury ( AOR , 0.56 ; 95 % CI , 0.32 - 0.96 ) , and injury requiring medical attention ( AOR , 0.46 ; 95 % CI , 0.30 - 0.70 ) . Quality -of-life scores were unaffected by the intervention . CONCLUSION Education and systems for medication review conducted by GPs can be used to improve use of medicines . These interventions are associated with a reduction in falls among older people , without adverse effects on quality of life BACKGROUND Although psychoactive medications have substantial side effects in the elderly , these drugs are used frequently in nursing homes . Few interventions have succeeded in changing this situation , and little is known about the clinical effects of such interventions . METHODS We studied six matched pairs of nursing homes ; at one r and omly selected nursing home in each pair , physicians , nurses , and aides participated in an educational program in geriatric psychopharmacology . At base line we determined the type and quantity of drugs received by all residents ( n = 823 ) , and a blinded observer performed st and ardized clinical assessment s of the residents who were taking psychoactive medications . After the five-month program , drug use and patient status were reassessed . RESULTS Scores on an index of psychoactive-drug use , measuring both the magnitude and the probable inappropriateness of medication use , declined significantly more in the nursing homes in which the program was carried out ( experimental nursing homes ) than in the control nursing homes ( decrease , 27 percent vs. 8 percent ; P = 0.02 ) . The use of antipsychotic drugs was discontinued in more residents in the experimental nursing homes than in the control nursing homes ( 32 percent vs. 14 percent ) ; the comparable figures for the discontinuation of long-acting benzodiazepines were 20 percent vs. 9 percent , and for antihistamine hypnotics , 45 percent vs. 21 percent . In the experimental nursing homes residents who were initially taking antipsychotic drugs showed less deterioration on several measures of cognitive function than similar residents in the control facilities , but they were more likely to report depression . Those who were initially taking benzodiazepines or antihistamine hypnotic agents reported less anxiety than controls but had more loss of memory . Most other measures of clinical status remained unchanged in both groups . CONCLUSIONS An educational program targeted to physicians , nurses , and aides can reduce the use of psychoactive drugs in nursing homes without adversely affecting the overall behavior and level of functioning of the residents BACKGROUND Different methods have previously been tested to affect GPs ' prescribing habits . Attention has been drawn to benzodiazepines and antipsychotic drugs that are associated with several adverse effects in the elderly . OBJECTIVE To evaluate if educational outreach visits to GP practice s can affect the prescribing of benzodiazepines and antipsychotic drugs to the elderly and to evaluate the opinions of the participating GPs on such education . METHODS In the county of Skåne , Sweden , 41 GP practice s were invited to participate in educational outreach visits . Fifteen GP practice s accepted the invitation . Practice s were r and omised to active ( 8 practice s , 23 physicians ) and control group ( 7 practice s , 31 physicians ) . After the educational outreach visits prescribing of benzodiazepines and antipsychotic drugs to patients 65 years or older were measured for 1 year . The control group participated in the education after the study period . The opinions of GPs on educational outreach visits were evaluated . RESULTS One year after the educational outreach visits there were significant decreases in the active group compared to control group in the prescribing of medium- and long-acting benzodiazepines and total benzodiazepines but not so for antipsychotic drugs . CONCLUSIONS Educational outreach visits can be effective in modifying GPs ' prescribing habits . We have shown this to be so for prescribing of benzodiazepines to elderly patients in primary health care . Educational outreach visits are also very well appreciated by participating GPs OBJECTIVE This study investigated the effects of general practitioner , patient , and prescription characteristics on the reduction of long-term benzodiazepine prescribing by sending a letter to chronic users . The data were analyzed with a method respecting the hierarchical data structure . STUDY DESIGN AND SETTING Data were obtained from 8,170 chronic users nested in 147 general practice s. One thous and two hundred fifty-six chronic users in 19 general practice s received a letter with the advice to reduce or stop the use of benzodiazepines after the general practitioners had attended a course on benzodiazepine use . In a three-level r and om intercept multilevel regression model , long-term prescribing of benzodiazepines was the dependent variable . RESULTS The reduction in benzodiazepine prescribing was significantly larger in the intervention than in the control group : 16 % after 6 months and 14 % after 12 months , respectively . The age of the patient , gender , and the interaction between age and gender were significant . The combination of the duration ( long acting or short acting ) with the type of benzodiazepine ( anxiolytic or hypnotic ) was an important pharmacological baseline covariate . CONCLUSIONS The reduction of benzodiazepine prescribing was mainly explained by the letter intervention and individual patient characteristics . Multilevel analysis was a worthwhile method for application in this study with its unbalanced design AIMS To evaluate whether a year long clinical pharmacy program involving development of professional relationships , nurse education on medication issues , and individualized medication review s could change drug use , mortality and morbidity in nursing home residents . METHODS A cluster r and omised controlled trial , where an intervention home was matched to three control homes , was used to examine the effect of the clinical pharmacy intervention on resident outcomes . The study involved 905 residents in 13 intervention nursing homes and 2325 residents in 39 control nursing homes in south-east Queensl and and north-east New South Wales , Australia . The outcome measures were : continuous drug use data from government prescription subsidy cl aims , cross-sectional drug use data on prescribed and administered medications , deaths and morbidity indices ( hospitalization rates , adverse events and disability indices ) . RESULTS This intervention result ed in a reduction in drug use with no change in morbidity indices or survival . Differences in nursing home characteristics , as defined by cluster analysis with SUDAAN , negated intervention-related apparent significant improvements in survival . The use of benzodiazepines , nonsteroidal anti-inflammatory drugs , laxatives , histamine H2-receptor antagonists and antacids was significantly reduced in the intervention group , whereas the use of digoxin and diuretics remained similar to controls . Overall , drug use in the intervention group was reduced by 14.8 % relative to the controls , equivalent to an annual prescription saving of A64 dollars per resident ( approximately 25 pound sterling ) . CONCLUSIONS This intervention improved nursing home resident outcomes related to changes in drug use and drug-related expenditure . The continuing divergence in both drug use and survival at the end of the study suggests that the difference would have been more significant in a larger and longer study , and even more so using additional instruments specific for measuring outcomes related to changes in drug use OBJECTIVES To evaluate the effects of an educational program to reduce antipsychotic use in nursing homes that had high use rates post-OBRA-87 and to identify factors that predicted antipsychotic withdrawal or 50 % or greater dose reduction . DESIGN / SETTING A r and omized controlled trial ( RCT ) of the educational program ( nursing home the unit of r and omization and analysis ) was conducted in 12 Tennessee nursing homes ( 6 education/6 control ) . Cohort analysis in baseline antipsychotic users identified factors predicting withdrawal or dose reduction . SUBJECTS The RCT analysis included 1152 patients in the homes at baseline and 6 months . The cohort analysis included 133 baseline antipsychotic users in the five education homes able to implement the recommendations of the educational program . OUTCOME MEASURES Change in days of antipsychotic use per 100 days of nursing home residence , withdrawal from antipsychotics , reduction in antipsychotic dose by 50 % or more . RESULTS Following the educational intervention , use of antipsychotics in the six education homes decreased from 25.3 days per 100 at baseline to 19.7 days per 100 by month 6 , a 23 % reduction relative to control homes ( P = .014 ) . In the withdrawal analysis , 44 ( 33 % ) of 133 baseline antipsychotic users were withdrawn . Factors at baseline predicting successful withdrawal were low antipsychotic dose , no use of benzodiazepines or antidepressants , and behavioral symptoms score below the median . However , although an additional 22 patients had dose reductions > or = 50 % , none of the predictors of withdrawal were associated with dose reductions . CONCLUSIONS Focused provider education programs may facilitate antipsychotic reduction above and beyond that attributable to regulatory changes . Patients who are poor c and i date s for total antipsychotic withdrawal may tolerate substantial dose reductions , which should reduce their risk of adverse antipsychotic effects AIM This study set out to assess the effect of a letter from the general practitioner , suggesting a reduction in the use of benzodiazepines , and whether the impact of the letter could be increased by the addition of information on how to tackle drug reduction . METHOD Two hundred and nine long-term users of benzodiazepines in general practice were divided into three groups : two intervention groups and a control group . The first intervention group received a letter from their general practitioner asking that benzodiazepine use be gradually reduced and perhaps , in time , stopped . The second intervention group received the same letter plus four information sheets at monthly intervals , design ed to assist drug reduction : The mean age of the 209 people was 69 years ( age range 34 - 102 years ) . RESULTS After six months , both intervention groups had reduced their consumption to approximately two thirds of the original intake of benzodiazepines and there was a statistically significant difference between the intervention groups and the control group . Eighteen per cent of those receiving the interventions received no prescriptions at all during the six month monitoring period . CONCLUSION The results indicate that a simple intervention can have a considerable effect on the use of hypnotic and anxiolytic drugs , even with a sample of elderly users Long-term use of benzodiazepines ( BZDs ) has been linked with an array of negative health consequences and increased medical costs and social burden . In this study , we sought to investigate the factors accounting for differential risks in the process from incident BZD use to long-term use and discontinuation in the general population . On the basis of a r and om sample of 187,413 people enrolled in Taiwan 's National Health Insurance program on January 1 , 2000 , data of 2000 - 2002 healthcare and pharmacological services utilization were retrieved . Long-term use ( LTU ) was defined by having received BZD prescriptions for 180 or more days within any given calendar year . Multivariate logistic regression analyses were carried out to assess the strength of associations while adjusting for the effects of individual sociodemographics , service providers , and pharmacological agents simultaneously . Results indicated that males , elderly , and those with physical or mental disorders were more likely to become long-term users of BZDs . Having received BZD prescriptions in multiple pharmacological agents , short-acting or mixed-type agents , and hypnotic indication were associated with a roughly 2- to 5-fold increased risk of BZD LTU soon after prescription initiation . With respect to discontinuation , the effects of pharmacological characteristics seem more salient as compared to those of individual and service-provider factors . Future strategies targeting individual factors and modifying service-provider prescription behaviors may be considered to reduce possible negative consequences of BZD LTU BACKGROUND We design ed this observational cohort study to assess the association between patient-centered communication in primary care visits and subsequent health and medical care utilization . METHODS We selected 39 family physicians at r and om , and 315 of their patients participated . Office visits were audiotaped and scored for patient-centered communication . In addition , patients were asked for their perceptions of the patient-centeredness of the visit . The outcomes were : ( 1 ) patients ' health , assessed by a visual analogue scale on symptom discomfort and concern ; ( 2 ) self-report of health , using the Medical Outcomes Study Short Form-36 ; and ( 3 ) medical care utilization variables of diagnostic tests , referrals , and visits to the family physician , assessed by chart review . The 2 measures of patient-centeredness were correlated with the outcomes of visits , adjusting for the clustering of patients by physician and controlling for confounding variables . RESULTS Patient-centered communication was correlated with the patients ' perceptions of finding common ground . In addition , positive perceptions ( both the total score and the subscore on finding common ground ) were associated with better recovery from their discomfort and concern , better emotional health 2 months later , and fewer diagnostic tests and referrals . CONCLUSIONS Patient-centered communication influences patients ' health through perceptions that their visit was patient centered , and especially through perceptions that common ground was achieved with the physician . Patient-centered practice improved health status and increased the efficiency of care by reducing diagnostic tests and referrals Minimal intervention strategies to decrease long-term benzodiazepine use have not yet been evaluated in large primary care based studies with a blinded control condition and a long follow-up period . The purpose of this study was to assess the effects of a letter with a discontinuation advice sent to long-term benzodiazepine users in family practice followed by an evaluation consultation offer . The experimental group consisted of 2425 long-term benzodiazepine users , 1707 of whom were addressed by a discontinuation letter and an evaluation consultation offer . The control group consisted of 1821 long-term users . Primary endpoints were the number of prescribed daily dosages ( PDD ) and the percentage of subjects without prescription ( quitters ) . At 21 months a reduction in benzodiazepine prescription of 26 % was observed in the experimental group , versus 9 % in the control group ( PDD difference=12.5 ; 95%-ci : 8.2 - 16.8 ) . In the experimental group 13 % and in the control group 5 % of the study completers were benzodiazepine prescription free through the full follow-up period ( RR=2.6 ; 95%-ci : 2.0 - 3.4 ) . The percentage of quitters at short-term ( 6 months ) was 24 % in the experimental group versus 12 % in the control group ( RR=2.1 ; 95%-ci : 1.8 - 2.4 ) . It is concluded that this intervention strategy steadily reduces long-term benzodiazepine use in family practice IMPORTANCE The American Board of Internal Medicine Foundation Choosing Wisely Campaign recommends against the use of benzodiazepine drugs for adults 65 years and older . The effect of direct patient education to catalyze collaborative care for reducing inappropriate prescriptions remains unknown . OBJECTIVE To compare the effect of a direct-to-consumer educational intervention against usual care on benzodiazepine therapy discontinuation in community-dwelling older adults . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized trial ( EMPOWER [ Eliminating Medications Through Patient Ownership of End Results ] study [ 2010 - 2012 , 6-month follow-up ] ) . Community pharmacies were r and omly allocated to the intervention or control arm in nonstratified , blocked groups of 4 . Participants ( 303 long-term users of benzodiazepine medication aged 65 - 95 years , recruited from 30 community pharmacies ) were screened and enrolled prior to r and omization : 15 pharmacies r and omized to the educational intervention included 148 participants and 15 pharmacies r and omized to the " wait list " control included 155 participants . Participants , physicians , pharmacists , and evaluators were blinded to outcome assessment . INTERVENTIONS The active arm received a deprescribing patient empowerment intervention describing the risks of benzodiazepine use and a stepwise tapering protocol . The control arm received usual care . MAIN OUTCOMES AND MEASURES Benzodiazepine therapy discontinuation at 6 months after r and omization , ascertained by pharmacy medication renewal profiles . RESULTS A total of 261 participants ( 86 % ) completed the 6-month follow-up . Of the recipients in the intervention group , 62 % initiated conversation about benzodiazepine therapy cessation with a physician and /or pharmacist . At 6 months , 27 % of the intervention group had discontinued benzodiazepine use compared with 5 % of the control group ( risk difference , 23 % [ 95 % CI , 14%-32 % ] ; intracluster correlation , 0.008 ; number needed to treat , 4 ) . Dose reduction occurred in an additional 11 % ( 95 % CI , 6%-16 % ) . In multivariate subanalyses , age greater than 80 years , sex , duration of use , indication for use , dose , previous attempt to taper , and concomitant polypharmacy ( 10 drugs or more per day ) did not have a significant interaction effect with benzodiazepine therapy discontinuation . CONCLUSIONS AND RELEVANCE Direct-to-consumer education effectively elicits shared decision making around the overuse of medications that increase the risk of harm in older adults . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01148186 We compared the effect of abrupt discontinuation of therapeutic doses of short half-life and long half-life benzodiazepines in 57 benzodiazepine-dependent patients ( daily use , greater than 1 year ) . Despite the use of a mean daily dose of 14.1 mg of diazepam equivalents , there were notable residual symptoms of anxiety and depression present at intake ( Hamilton Rating Scale for Anxiety score , 17.0 ; Hamilton Rating Scale for Depression score , 14.0 ) . Benzodiazepine intake was stabilized for 3 weeks before double-blind assignment to placebo ( n = 47 ) , or continued benzodiazepine use ( n = 10 ) . Clinical assessment s were performed daily , including benzodiazepine plasma levels . Depending on the outcome criteria used , anywhere from 58 % to 100 % of patients were judged to have experienced a withdrawal reaction , with a peak severity at 2 days for short half-life and 4 to 7 days for long half-life benzodiazepines . Relapse onto benzodiazepines occurred in 27 % of patients who were receiving long half-life benzodiazepines and in 57 % of patients who were receiving short half-life benzodiazepines . Baseline predictors of relapse were nonpanic diagnoses , a higher benzodiazepine dose , and a higher Eysenck neuroticism score . A short half-life and higher daily doses were associated with greater withdrawal severity , as were personality traits , such as dependency and neuroticism , less education and higher baseline levels of anxious and depressive symptoms . Patients who were able to remain free of benzodiazepines for at least 5 weeks obtained lower levels of anxiety than before benzodiazepine discontinuation . These results provide a detailed picture of the symptoms , time course , and multidimensional determinants of the benzodiazepine withdrawal syndrome BACKGROUND The long-term use of benzodiazepines is highly prevalent in developed societies and is not devoid of risks . Withdrawing patients from these drugs is often difficult . Tapering off benzodiazepines has been shown to be a good strategy for discontinuing their long-term use . AIM To establish the efficacy of an intervention programme for reducing the chronic use of benzodiazepines . DESIGN OF STUDY R and omised , two-arm , parallel , non-blinded controlled trial . SETTING Three urban healthcare centres covering a population of 50,000 inhabitants ( Mallorca , Spain ) . METHOD Adult patients ( n = 139 ) taking benzodiazepines daily for more than a year and visited by their family physician were r and omised into an intervention group ( n = 73 ) that received st and ardised advice and a tapering off schedule with biweekly follow-up visits , or into a control group ( n = 66 ) , that was managed following routine clinical practice . Both were followed for a year . RESULTS Patients achieved withdrawal or reduced their dose by at least 50 % after 6 and 12 months . Abstinence and withdrawal symptoms were also measured . Both groups were homogeneous for personal , clinical and psychological characteristics and for benzodiazepine use . Only two patients from each group were lost to follow-up . After 12 months , 33 ( 45.2 % ) patients in the intervention group and six ( 9.1 % ) in the control group had discontinued benzodiazepine use ; relative risk = 4.97 ( 95 % confidence interval [ CI ] = 2.2 to 11.1 ) , absolute risk reduction = 0.36 ( 95 % CI = 0.22 to 0.50 ) . For every three interventions , one patient achieved withdrawal . Sixteen ( 21.9 % ) subjects from the intervention group and 11 ( 16.7 % ) controls reduced their initial dose by more than 50 % . CONCLUSION St and ardised advice given by the family physician , together with a tapering off schedule , is effective for withdrawing patients from long-term benzodiazepine use and is feasible in primary care Background : Benzodiazepine ( BZD ) dependence among seniors is an understudied problem . Objective : Identify the factors associated with BZD dependence . Method : Face-to-face computer-assisted interviews were conducted in the homes of 2,785 persons aged 65 years or older , r and omly selected . Results : Nine- and -a-half percent of BZD users met DSM-IV-TR criteria for BZD dependence . Factors associated with BZD dependence are being a woman , and having cognitive impairment , panic disorders , suicidal ideations , and a degree of embarrassment in obtaining help for emotional problem . Discussion : Nurses should be better positioned to identify those elderly users of BZDs who are more likely to be dependent and to address the problem through BZD withdrawal program In order to measure the effect of industry-independent information on the prescribing of benzodiazepines in general practice , 128 primary practitioners were r and omly allocated to three intervention groups after stratification by year of graduation . One third of the participating physicians were forwarded written information about the indications and limitations of benzodiazepines , another third received both written and oral information , and the remaining third ( the control group ) obtained no information at all . A comparison of the number of benzodiazepines prescribed per 100 patient contacts with prescription before and after the intervention showed an average decrease of 3 % in the control group , of 14 % in physicians who received only written information , and of 24 % in physicians who were given additional oral information . Post hoc pairwise comparisons revealed a significant difference at the 1 % level in the number of benzodiazepines prescribed between physicians who received both written and oral information and the control group . A follow-up survey conducted 4 weeks after the intervention showed that the oral information campaign positively affected physicians ' attitudes about the value of oral drug information from an industry-independent source BACKGROUND It is recommended that long-term users of benzodiazepines in general practice be withdrawn from their medication where possible . AIM A study was undertaken to assess the effectiveness of minimal intervention delivered by general practitioners in helping chronic users of benzodiazepines to withdraw from their medication , and to determine the psychological sequelae on patients of such intervention . METHOD Patients taking benzodiazepines regularly for at least one year were recruited by their general practitioner and allocated either to a group receiving brief advice during one consultation supplemented by a self-help booklet or to a control group who received routine care . The patients completed the 12-item general health question naire and a benzodiazepine withdrawal symptom question naire at the outset of the study and at three and six months after this . RESULTS Eighteen per cent of patients in the intervention group ( 9/50 ) had a reduction in benzodiazepine prescribing recorded in the notes compared with 5 % of the 55 patients in the control group ( P < 0.05 ) . In the intervention group , 63 % of patients had a score of two or more on the general health question naire at baseline compared with 52 % at six months . Of the 20 intervention patients reporting benzodiazepine reduction , 60 % had a score of two or more at baseline compared with 40 % at six months . Intervention patients had significantly more qualitative , but not quantitative , withdrawal symptoms at six months compared with baseline . Consultation rates were not increased in the intervention group . CONCLUSION The study indicates that some chronic users can successfully reduce their intake of benzodiazepines with simple advice from the general practitioner and a self-help booklet . This type of intervention does not lead to psychological distress or increased consultation OBJECTIVES Drug use review is used by both the public and private sector to influence prescribing behavior and patient drug use . Past interventions mailed to prescribers have had mixed results . The objective was to evaluate the effect of a one-time , mailed intervention on subsequent use of sedative hypnotic medication . METHODS An experimental design was used . The intervention contained guidelines for the use of sedative hypnotics , a prescriber profile detailing sedative hypnotic prescribing , and a patient profile . Clustering of patients and their shared prescribers was done to avoid contamination bias and statistical problems associated with a lack of independence of observations . Subjects were 189 Washington State Medicaid recipients who had received at least one tablet per day of a sedative hypnotic medication for 1 year and their prescribing physicians or ( when information about the physician was lacking ) the dispensing pharmacy . RESULTS A significant reduction in the use of targeted sedative hypnotic medications was measured in the intervention group ( -27.6 % ) versus the control group ( -8.5 % ) . In the intervention group , 9.4 % of patients began a new prescription for a benzodiazepine not targeted by the drug use review , whereas no control patients had new use of nontarget benzodiazepines . CONCLUSIONS The intervention achieved a statistically significant decrease in targeted drug use , and the amount of reduction is likely to have decreased the risk of fractures associated with benzodiazepine use . This study adds to the recent evidence that mailed drug use review interventions can have a desirable impact on patient drug use OBJECTIVE The aim of this pilot prospect i ve study was to investigate the relationships between general practitioners ( GPs ) empathy , patient enablement , and patient-assessed outcomes in primary care consultations in an area of high socio-economic deprivation in Scotl and . METHODS This prospect i ve study was carried out in a five-doctor practice in an area of high socioeconomic deprivation in Scotl and . Patients ' views on the consultation were gathered using the Consultation and Relational Empathy ( CARE ) Measure and the Patient Enablement Instrument ( PEI ) . Changes in main complaint and well-being 1 month after the contact consultation were gathered from patients by postal question naire . The effect of GP empathy on patient enablement and prospect i ve change in outcome was investigated using structural equation modelling . RESULTS 323 patients completed the initial question naire at the contact consultation and of these 136 ( 42 % ) completed and returned the follow-up question naire at 1 month . Confirmatory factor analysis confirmed the construct validity ofthe CARE Measure , though omission of two ofthe six PEI items was required in order to reach an acceptable global data fit . The structural equation model revealed a direct positive relationship between GP empathy and patient enablement at contact consultation and a prospect i ve relationship between patient enablement and changes in main complaint and well-being at 1 month . CONCLUSION In a high deprivation setting , GP empathy is associated with patient enablement at consultation , and enablement predicts patient-rated changes 1 month later . Further larger studies are desirable to confirm or refute these findings . PRACTICE IMPLICATION S Ways of increasing GP empathy and patient enablement need to be established in order to maximise patient outcomes . Consultation length and relational continuity of care are known factors : the benefit of training and support for GPs needs to be further investigated |
2,220 | 30,811,484 | RESULTS Findings from both the meta- analysis and systematic review revealed that overall , re appraisal interventions are effective in attenuating subjective responsivity to stress .
On one h and , findings may suggest a promising avenue for the effective management of self-reported stress and optimization of stress responses . | BACKGROUND The beliefs we hold about stress play an important role in coping with stressors .
Various theoretical frameworks of stress point to the efficacy of reframing stress-related information through brief re appraisal interventions in order to promote adaptive coping .
PURPOSE The goal of the current meta- analysis and systematic review is to substantiate the efficacy of re appraisal interventions on stress responsivity compared to control conditions .
Differences in experimental method ologies ( e.g. , type of stressor used , timing of re appraisal intervention , and content of intervention instructions ) will be examined to further delineate their effects on intervention outcomes . | Background Fast-acting medications for the management of anxiety are important to patients and society . Measuring early onset , however , requires a sensitive and clinical ly responsive tool . This study evaluates the psychometric properties of a patient-reported Global Anxiety - Visual Analog Scale ( GA-VAS ) . Methods Data from a double-blind , r and omized , placebo-controlled study of lorazepam and paroxetine in patients with Generalized Anxiety Disorder were analyzed to assess the reliability , validity , responsiveness , and utility of the GA-VAS . The GA-VAS was completed at clinic visits and at home during the first week of treatment . Targeted psychometric analyses — test-retest reliabilities , validity correlations , responsiveness statistics , and minimum important differences — were conducted . Results The GA-VAS correlates well with other anxiety measures , at Week 4 , r = 0.60 ( p < 0.0001 ) with the Hamilton Rating Scale for Anxiety and r = 0.74 ( p < 0.0001 ) with the Hospital Anxiety and Depression Scale - Anxiety subscale . In terms of convergent and divergent validity , the GA-VAS correlated -0.54 ( p < 0.0001 ) , -0.48 ( p < 0.0001 ) , and -0.68 ( p < 0.0001 ) with the SF-36 Emotional Role , Social Function , and Mental Health subscales , respectively , but correlated much lower with the SF-36 physical functioning subscales . Preliminary minimum important difference estimates cluster between 10 and 15 mm . Conclusions The GA-VAS is capable of validly and effectively capturing a reduction in anxiety as quickly as 24 hours post-dose Cognitive re appraisal can foster emotion regulation , yet less is known about whether cognitive re appraisal alters neuroendocrine stress reactivity . Some initial evidence suggests that although long-term training in cognitive behavioral therapy techniques ( which include re appraisal as a primary training component ) can reduce cortisol reactivity to stress , some studies also suggest that re appraisal is associated with heightened cortisol stress reactivity . To address this mixed evidence , the present report describes two experimental studies that r and omly assigned young adult volunteers to use cognitive re appraisal while undergoing laboratory stressors . Relative to the control condition , participants in the re appraisal conditions showed greater peak cortisol reactivity in response to a socially evaluative speech task ( Experiment 1 , N=90 ) and to a physical pain cold pressor task ( Experiment 2 , N=94 ) . Participants in the cognitive re appraisal group also reported enhanced anticipatory psychological appraisal s of self-efficacy and control in Experiment 2 and greater post-stressor self-efficacy . There were no effects of the re appraisal manipulation on positive and negative subjective affect , pain , or heart rate in either experiment . These findings suggest that although cognitive re appraisal fosters psychological perceptions of self-efficacy and control under stress , this effortful emotion regulation strategy in the short-term may increase cortisol reactivity . Discussion focuses on promising psychological mechanisms for these cognitive re appraisal effects Research ers have theorized that changing the way we think about our bodily responses can improve our physiological and cognitive reactions to stressful events . However , the underlying processes through which mental states improve downstream outcomes are not well understood . To this end , we examined whether reappraising stress-induced arousal could improve cardiovascular outcomes and decrease attentional bias for emotionally negative information . Participants were r and omly assigned to either a re appraisal condition in which they were instructed to think about their physiological arousal during a stressful task as functional and adaptive , or to 1 of 2 control conditions : attention reorientation and no instructions . Relative to controls , participants instructed to reappraise their arousal exhibited more adaptive cardiovascular stress responses-increased cardiac efficiency and lower vascular resistance- and decreased attentional bias . Thus , reappraising arousal shows physiological and cognitive benefits . Implication s for health and potential clinical applications are discussed OBJECTIVE This study sought to examine the relationship among the amount of stress , the perception that stress affects health , and health and mortality outcomes in a nationally representative sample of U.S. adults . METHODS Data from the 1998 National Health Interview Survey were linked to prospect i ve National Death Index mortality data through 2006 . Separate logistic regression models were used to examine the factors associated with current health status and psychological distress . Cox proportional hazard models were used to determine the impact of perceiving that stress affects health on all-cause mortality . Each model specifically examined the interaction between the amount of stress and the perception that stress affects health , controlling for sociodemographic , health behavior , and access to health care factors . RESULTS 33.7 % of nearly 186 million ( unweighted n = 28,753 ) U.S. adults perceived that stress affected their health a lot or to some extent . Both higher levels of reported stress and the perception that stress affects health were independently associated with an increased likelihood of worse health and mental health outcomes . The amount of stress and the perception that stress affects health interacted such that those who reported a lot of stress and that stress impacted their health a lot had a 43 % increased risk of premature death ( HR = 1.43 , 95 % CI [ 1.2 , 1.7 ] ) . CONCLUSIONS High amounts of stress and the perception that stress impacts health are each associated with poor health and mental health . Individuals who perceived that stress affects their health and reported a large amount of stress had an increased risk of premature death Prior research suggests that stress can be harmful in high-stakes context s such as negotiations . However , few studies actually measure stress physiologically during negotiations , nor do studies offer interventions to combat the potential negative effects of heightened physiological responses in negotiation context s. In the current research , we offer evidence that the negative effects of cortisol increases on negotiation performance can be reduced through a re appraisal of anxiety manipulation . We experimentally induced adaptive appraisal s by r and omly assigning 97 male and female participants to receive either instructions to appraise their anxiety as beneficial to the negotiation or no specific instructions on how to appraise the situation . We also measured participants ’ cortisol responses prior to and following the negotiation . Results revealed that cortisol increases were positively related to negotiation performance for participants who were told to view anxiety as beneficial , and not detrimental , for negotiation performance ( appraisal condition ) . In contrast , cortisol increases were negatively related to negotiation performance for participants given no instructions on appraising their anxiety ( control condition ) . These findings offer a means through which to combat the potentially deleterious effects of heightened cortisol reactivity on negotiation outcomes Background The consequences of stress are typically regarded from a deficit-oriented approach , conceptualizing stress to be entirely negative in its outcomes . This approach is unbalanced , and may further hinder individuals from engaging in adaptive coping . In the current study , we explored whether negative views and beliefs regarding stress interacted with a stress framing manipulation ( positive , neutral and negative ) on measures of stress reactivity for both psychosocial and physiological stressors . Method Ninety participants were r and omized into one of three framing conditions that conceptualized the experience of stress in balanced , unbalanced-negative or unbalanced-positive ways . After watching a video on stress , participants underwent a psychosocial ( Trier Social Stress Test ) , or a physiological ( CO2 challenge ) method of stress-induction . Subjective and objective markers of stress were assessed . Results Most of the sample d population regarded stress as negative prior to framing . Further , subjective and objective reactivity were greater to the TSST compared to the CO2 challenge . Additionally , significant cubic trends were observed in the interactions of stress framing and stress-induction method ologies on heart rate and blood pressure . Balanced framing conditions in the TSST group had a significantly larger decrease in heart rate and diastolic blood pressure following stress compared to the positive and negative framing conditions . Conclusion Findings confirmed a deficit-orientation of stress within the sample d population . In addition , results highlighted the relative efficacy of the TSST compared to CO2 as a method of stress provocation . Finally , individuals in framing conditions that posited stress outcomes in unbalanced manners responded to stressors less efficiently . This suggests that unbalanced framing of stress may have set forth unrealistic expectations regarding stress that later hindered individuals from adaptive responses to stress . Potential benefits of alternative conceptualizations of stress on stress reactivity are discussed , and suggestions for future research are made OBJECTIVES Verbally administered numerical rating scales ( NRSs ) from 0 to 10 are often used to measure pain , but they have not been vali date d in the emergency department ( ED ) setting . The authors wished to assess the comparability of the NRS and visual analog scale ( VAS ) as measures of acute pain , and to identify the minimum clinical ly significant difference in pain that could be detected on the NRS . METHODS This was a prospect i ve cohort study of a convenience sample of adults presenting with acute pain to an urban ED . Patients verbally rated pain intensity as an integer from 0 to 10 ( 0 = no pain , 10 = worst possible pain ) , and marked a 10-cm horizontal VAS bounded by these descriptors . VAS and NRS data were obtained at presentation , 30 minutes later , and 60 minutes later . At 30 and 60 minutes , patients were asked whether their pain was " much less , " " a little less , " " about the same , " " a little more , " or " much more . " Differences between consecutive pairs of measurements on the VAS and NRS obtained at 30-minute intervals were calculated for each of the five categories of pain descriptor . The association between VAS and NRS scores was expressed as a correlation coefficient . The VAS scores were regressed on the NRS scores in order to assess the equivalence of the measures . The mean changes associated with descriptors " a little less " or " a little more " were combined to define the minimum clinical ly significant difference in pain measured on the VAS and NRS . RESULTS Of 108 patients entered , 103 provided data at 30 minutes and 86 at 60 minutes . NRS scores were strongly correlated to VAS scores at all time periods ( r = 0.94 , 95 % CI = 0.93 to 0.95 ) . The slope of the regression line was 1.01 ( 95 % CI = 0.97 to 1.06 ) and the y-intercept was -0.34 ( 95 % CI = -0.67 to -0.01 ) . The minimum clinical ly significant difference in pain was 1.3 ( 95 % CI = 1.0 to 1.5 ) on the NRS and 1.4 ( 95 % CI = 1.1 to 1.7 ) on the VAS . CONCLUSIONS The findings suggest that the verbally administered NRS can be substituted for the VAS in acute pain measurement ABSTRACT Background and Objectives : This study examined the effects of arousal re appraisal on cardiovascular responses , dem and and re source evaluations , self-confidence , performance and attention under pressurized conditions . A recent study by Moore et al. [ 2015 . Reappraising threat : How to optimize performance under pressure . Journal of Sport and Exercise Psychology , 37(3 ) , 339–343 . doi:10.1123/jsep.2014 - 0186 ] suggested that arousal re appraisal is beneficial to the promotion of challenge states and leads to improvements in single-trial performance . This study aim ed to further the work of Moore and colleagues ( 2015 ) by examining the effects of arousal re appraisal on cardiovascular responses , dem and and re source evaluations , self-confidence , performance and attention in a multi-trial pressurized performance situation . Design and Methods : Participants were r and omly assigned to either an arousal re appraisal intervention or control condition , and completed a pressurized dart throwing task . The intervention encouraged participants to view their physiological arousal as facilitative rather than debilitative to performance . Measures of cardiovascular reactivity , dem and and re source evaluations , self-confidence , task performance and attention were recorded . Results : The re appraisal group displayed more favorable cardiovascular reactivity and reported higher re source evaluations and higher self-confidence than the control group but no task performance or attention effects were detected . Conclusion : These findings demonstrate the strength of arousal re appraisal in promoting adaptive stress responses , perceptions of re sources and self-confidence Background and objectives : Few studies related to the impact of different emotion regulation strategies on anxiety have used externally and ecologically valid emotion-eliciting stimuli or Eastern population s. The present study compares the effects of re appraisal , suppression , and acceptance on anxiety induced by a simulated job interview in a Chinese sample . Methods : Eighty-two subjects were r and omly assigned to one of four instructions : re appraisal , suppression , acceptance , or no-regulation strategies during a simulated job interview . Anxiety was assessed with an observer-based behavior rating scale during the interview and the State Anxiety Inventory before , during , and after the interview . Results : A repeated- measures MANOVA indicated a significantly greater reduction in anxiety in the re appraisal and acceptance groups compared to the control group during the interview ( re appraisal : d = 1.42 ; acceptance : d = 1.30 ; each p < .001 ) , but not during the recovery stage . The suppression and control group did not differ in any stage . Suppression led to a higher ( pmax < .04 ) anxiety than re appraisal /acceptance in the anticipation ( d = 0.65/0.68 ) , interview ( d = 0.87/0.79 ) , and recovery stages ( d = 0.94/1.03 ) . No significant differences were found between re appraisal and acceptance . Conclusions : In Chinese students re appraisal and acceptance seem to be more effective anxiety regulation strategies than suppression |
2,221 | 25,967,226 | Our analysis revealed that PEG-IFNα + lamivudine combination therapy produced better virological and biochemical responses than PEG-IFNα monotherapy in HBeAg-positive and HBeAg-negative patients at the end of treatment .
PEG-IFNα + adefovir dipivoxil achieved better seroconversion rate than PEG-IFNα in HBeAg-positive patients at the end of treatment .
The present findings demonstrated a beneficial response rate following PEG-IFNα combination therapy with nucelos(t)ides among HBeAg-positive and HBeAg-negative patients with CHB . | Conventional interferon alfa and nucleos(t)ide analogues , such as lamivudine , are frequently used for chronic hepatitis B ( CHB ) treatment , but are associated with adverse effects and viral resistance . | Current therapies for chronic hepatitis B ( CHB ) have a number of limitations , and better treatment options are needed . Peginterferon alpha-2a ( 40 kDa ) is superior to conventional interferon alpha-2a in the treatment of chronic hepatitis C. This is the first report on peginterferon alpha-2a ( 40 kDa ) in the treatment of CHB . In this phase II study , 194 patients with CHB not previously treated with conventional interferon-alpha were r and omized to receive weekly subcutaneous doses of peginterferon alpha-2a ( 40 kDa ) 90 , 180 or 270 microg , or conventional interferon alpha-2a 4.5 MIU three times weekly . Twenty-four weeks of therapy were followed by 24 weeks of treatment-free follow-up . All subjects were assessed for loss of hepatitis B e antigen ( HBeAg ) , presence of hepatitis B antibody ( anti-HBe ) , suppression of hepatitis B virus ( HBV ) DNA , and normalization of serum alanine transaminase ( ALT ) after follow-up . At the end of follow-up , HBeAg was cleared in 37 , 35 and 29 % of patients receiving peginterferon alpha-2a ( 40 kDa ) 90 , 180 and 270 microg , respectively , compared with 25 % of patients on conventional interferon alpha-2a . The combined response ( HBeAg loss , HBV DNA suppression , and ALT normalization ) of all peginterferon alpha-2a ( 40 kDa ) doses combined was twice that achieved with conventional interferon alpha-2a ( 24%vs 12 % ; P = 0.036 ) . All treatment groups were similar with respect to frequency and severity of adverse events . These results indicate that peginterferon alpha-2a ( 40 kDa ) is superior in efficacy to conventional interferon alpha-2a in chronic hepatitis B based on clearance of HBeAg , suppression of HBV DNA , and normalization of ALT BACKGROUND Treatment with adefovir dipivoxil for 48 weeks result ed in histologic , virologic , and biochemical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. We evaluated the effect of continued therapy as compared with cessation of therapy . METHODS One hundred eighty-five HBeAg-negative patients with chronic hepatitis B were assigned to receive 10 mg of adefovir dipivoxil or placebo once daily for 48 weeks ( ratio , 2:1 ) . After week 48 , patients receiving adefovir dipivoxil were again r and omly assigned either to receive an additional 48 weeks of the drug or to switch to placebo . Patients originally assigned to placebo were switched to adefovir dipivoxil . Patients treated with adefovir dipivoxil during weeks 49 through 96 were subsequently offered continued therapy . The primary end points were changes in hepatitis B virus ( HBV ) DNA and alanine aminotransferase levels . RESULTS Treatment with adefovir dipivoxil result ed in a median decrease in serum HBV DNA of 3.47 log copies per milliliter ( on a base-10 scale ) at 96 weeks and 3.63 log copies per milliliter at 144 weeks . HBV DNA levels were less than 1000 copies per milliliter in 71 percent of patients at week 96 and 79 percent at week 144 . In the majority of patients who were switched from adefovir dipivoxil to placebo , the benefit of treatment was lost ( median change in HBV DNA levels from baseline , -1.09 log copies per milliliter ; only 8 percent of patients had levels below 1000 copies per milliliter at week 96 ) . Side effects during weeks 49 through 144 were similar to those during the initial 48 weeks . Resistance mutations rtN236 T and rtA181V were identified in 5.9 percent of patients after 144 weeks . CONCLUSIONS In patients with HBeAg-negative chronic hepatitis B , the benefits achieved from 48 weeks of adefovir dipivoxil were lost when treatment was discontinued . In patients treated for 144 weeks , benefits were maintained , with infrequent emergence of viral resistance To evaluate the effect of interferon and the benefit of prednisolone pretreatment in Oriental patients with chronic active hepatitis B , 120 male Chinese patients were r and omly allocated to receive : 1 ) group A : a 4-week course of prednisolone followed by 2 weeks of no treatment and then a 12-week course of human lymphoblastoid interferon , 4 to 6 MU/m2 intramuscularly ; 2 ) group B : as group A , but with placebo given instead of prednisolone ; 3 ) group C : an 18-week course of placebo . Clearance of serum hepatitis B virus-DNA and HBeAg ( complete response ) was achieved in 21 % of group A , 5 % of group B and none of group C at the end of therapy ( A vs B : p = 0.054 ; A vs C : p < 0.01 ) . When assessed 12 months after the end of therapy , the complete response rate was 46 % in group A , 24 % in group B and 25 % in group C ( p < 0.05 ) . Those with baseline alanine transaminase < or = 200 U/l showed a better response to interferon following prednisolone withdrawal ( 48 % ) than with interferon therapy alone ( 20 % , p = 0.056 ) and no treatment ( 9 % , p < 0.01 ) . Those with a baseline serum hepatitis B virus-DNA < or = 1000 pg/ml also showed a higher complete response rate when pretreated with prednisolone ( 59 % ) than when treated with interferon alone ( 29 % , p = 0.084 ) or untreated ( 22 % , p < 0.03 ) . The strongest independent predictor of a response to treatment was prednisolone withdrawal ( p < 0.05 ) . None of the responders lost hepatitis B surface antigen . ( ABSTRACT TRUNCATED AT 250 WORDS To assess the impact of sequential therapy with adefovir dipivoxil ( ADV ) and pegylated interferon alfa-2a ( PEG-IFN ) on virological ( serum HBV-DNA ) and serological ( serum HBsAg ) response in 20 consecutive HBeAg-negative patients . Patients received ADV for 20 weeks , then ADV and PEG-IFN for 4 weeks and lastly PEG-IFN for 44 weeks . Serum HBV-DNA and HBsAg were assessed at baseline , during therapy ( weeks 20 , 44 and 68 ) and follow-up ( weeks 92 and 116 ) . Sustained virological response ( SVR ) was defined as serum HBV-DNA < 10 000 copies/mL ( partial ) or < 70 copies/mL ( complete ) 24 weeks after stopping treatment . A serological response was defined as a serum HBsAg decrease ≥1 log(10 ) IU/mL at the end of treatment . Baseline median serum HBV-DNA and HBsAg levels were 7.6 log(10 ) copies/mL and 3.8 log(10 ) IU/mL , respectively . Ten patients ( 50 % ) achieved SVR , six of them had partial response and four complete response . Four patients ( 20 % ) achieved serological response . Complete SVRs showed a major and steep decline in HBsAg level with a median decrease of 0.5 , 1.6 and 2.0 log(10 ) IU/mL at treatment week 20 , 44 and 68 , respectively . Partial SVRs showed a slight and slow decline in serum HBsAg level ( 0.1 , 0.4 , and 0.6 log IU/mL at weeks 20 , 44 and 68 , respectively ) . On-treatment serum HBsAg decrease had a high accuracy to predict SVR ( AUROC = 0.88 ) . Our results suggest that sequential therapy might be an interesting strategy for HBeAg-negative patients . Serum HBsAg kinetics seem to be an accurate tool to predict SVR . Large clinical trials are needed to explore this strategy with more potent analogues 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 Treatment with peginterferon α-2a ( PegIFN ) for 48 weeks is the st and ard of care for selected HBeAg-negative patients chronically infected with hepatitis B virus ( HBV ) , but with limited treatment efficacy . A study was undertaken to investigate whether treatment extension to 96 weeks improves the outcome in this patient population . Methods 128 HBeAg-negative patients ( 120 genotype D ) were r and omised to weekly 180 μg PegIFN for 48 weeks ( group A , n=51 ) , 180 μg PegIFN for 48 weeks followed by 135 μg weekly for an additional 48 weeks ( group B , n=52 ) or 180 μg PegIFN plus lamivudine ( 100 mg/day ) for 48 weeks then 135 μg PegIFN for 48 weeks ( group C , n=25 ) . Endpoints were alanine aminotransferase normalisation plus HBV DNA < 3400 IU/ml ( primary ) , HBV DNA < 2000 IU/ml and HBsAg clearance at 48 weeks after treatment . Results Forty-eight weeks after treatment , six patients in group A and 13 in group B achieved alanine aminotransferase normalisation plus HBV DNA < 3400 IU/ml ( 11.8 % vs 25.0 % , p=0.08 ) , 6 vs 15 patients had HBV DNA < 2000 IU/ml ( 11.8 % vs 28.8 % , p=0.03 ) , 0 vs 3 achieved HBsAg clearance ( 0 % vs 5.8 % , p=0.24 ) and 0 vs 5 had HBsAg < 10 IU/ml ( 0 % vs 9.6 % , p=0.06 ) . While extended PegIFN treatment was the strongest independent predictor of response , the combination with lamivudine did not improve responses . Discontinuation rates were similar among the groups ( 19.6 % , 23.1 % , 32.0 % , p=0.81 ) and were mostly due to PegIFN-related adverse events . Conclusions In HBeAg-negative genotype D patients with chronic hepatitis B , PegIFN treatment for 96 weeks was well tolerated and the post-treatment virological response improved significantly compared with 48 weeks of treatment . Trial registration number http:// Clinical Trials.gov registration number : NCT01095835 The focus of this study was to evaluate the safety and efficacy of sequential peginterferon α-2a ( Pegasys ) therapy for chronic hepatitis B with acute exacerbation [ ALT > 10 × upper limit of normal ( ULN ) , bilirubin < 2.0 mg/dL ] . Four groups of patients categorized by HBeAg status and treatment regimens were studied since May 2007 . Nineteen HBeAg-positive patients ( Group 1 ) had received entecavir pretreatment ( when ALT > 10 × ULN ) plus Pegasys ( 180 μg/kg/week , when ALT was 5–10 × ULN ) for 24 weeks . Thirteen HBeAg-negative patients ( Group 2 ) had the same protocol for 48 weeks . In both groups , entecavir was then discontinued 14 days after the initiation of Pegasys . The results were compared , respectively , to 35 HBeAg-positive patients ( Group 3 ) and 24 HBeAg-negative patients ( Group 4 ) , all with ALT > 5 × ULN , under continual entecavir monotherapy . The ALT levels of patients in Group 1 and 2 who had received entecavir pretreatment for a duration of 19.63 ± 3.34 days were below four times of ULN following 4 weeks of Pegasys treatment . At week 96 , the rates of sustained virological response were 69.2 % ( 9/13 ) and 80 % ( 8/10 ) , and the relapse rates were 23.1 % ( 3/13 ) and 11.2 % ( 1/9 ) for HBeAg-positive and HBeAg-negative patients with two-step Pegasys treatment , respectively . The HBeAg seroconversion rates were 46.2 % in Group 1 , and 42.1 % in Group 3 ; HBsAg loss rates were 15.4 % ( 2/13 ) in Group 1 , and 30 % ( 3/10 ) in Group 2 , whereas none achieved HBsAg loss with entecavir monotherapy ( Group 3 and 4 ) . The two-step Pegasys treatment offers an alternative , other than the nucleos(t)ides , for treating chronic hepatitis B with acute exacerbation and provides a safe , efficacious , short-term and finite strategy BACKGROUND & AIMS Durable post-treatment response is uncommon in chronic hepatitis B ( CHB ) patients on nucleos(t)ide analogue therapy . Response , response predictors and safety were assessed in patients who switched from long-term entecavir ( ETV ) to peginterferon alfa-2a . METHODS Hepatitis B e antigen (HBeAg)-positive CHB patients who had received ETV for 9 - 36 months , with HBeAg < 100 PEIU/ml and HBV DNA ⩽1000 copies/ml , were r and omised 1:1 to receive peginterferon alfa-2a 180 μg/week or ETV 0.5mg/day for 48 weeks . The primary endpoint was HBeAg seroconversion at week 48 ( Clinical Trials.gov : NCT00940485 ) . RESULTS 200 patients were r and omised ; 197 received ⩾1 study drug dose . Five patients who were anti-HBe-positive at baseline were excluded from the modified intention-to-treat population ( peginterferon alfa-2a , n = 94 ; ETV , n = 98 ) . Patients who switched to peginterferon alfa-2a achieved higher week 48 HBeAg seroconversion rates vs. those who continued ETV ( 14.9 % vs. 6.1 % ; p = 0.0467 ) . Only patients receiving peginterferon alfa-2a achieved HBsAg loss ( 8.5 % ) . Among peginterferon alfa-2a-treated patients with HBeAg loss and HBsAg < 1500 IU/ml at r and omisation , 33.3 % and 22.2 % achieved HBeAg seroconversion and HBsAg loss , respectively . Early on-treatment HBsAg decline predicted response at week 48 ; highest rates were observed in patients with week 12 HBsAg < 200 IU/ml ( HBeAg seroconversion , 66.7 % ; HBsAg loss , 77.8 % ) . Alanine aminotransferase elevations were not associated with viral rebound ( n = 38 ) . Peginterferon alfa-2a was well-tolerated . CONCLUSIONS For patients who achieve virological suppression with ETV , switching to a finite course of peginterferon alfa-2a significantly increases rates of HBeAg seroconversion and HBsAg loss . A response-guided approach may identify patients with the greatest chance of success YMDD variants of hepatitis B virus ( HBV ) emerge in some patients with chronic hepatitis B who receive lamivudine . YMDD variants were examined in 794 patients in 4 controlled studies of 1 year 's duration . The long-term effects of YMDD variants were examined in a subset of patients treated up to 4 years . YMDD variants were detected by polymerase chain reaction ( PCR ) and restriction fragment-length polymorphism assays . After 1 year , YMDD variants were detected in 81 ( 24 % ) of 335 patients . In these patients , the median serum HBV DNA concentration at 1 year was < 20 % of the baseline level , and serum alanine transaminase ( ALT ) levels and liver histologic findings had significantly improved . In patients with YMDD variants who were treated for up to 4 years , median HBV DNA and ALT levels showed improvements . Sex , baseline body mass index , and HBV DNA level were associated with emergence of YMDD variants . Patients with YMDD variants losing clinical response with a significant increase in the HBV DNA and ALT levels may require additional therapy BACKGROUND Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most . A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response . METHODS 307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy ( 100 microg/week pegylated interferon alfa-2b and 100 mg/day lamivudine ) or monotherapy ( 100 microg/week pegylated interferon alfa-2b and placebo ) for 52 weeks . During weeks 32 - 52 the pegylated interferon dose was 50 microg/week in both treatment groups . The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct , ten who lost HBeAg before the study start , and seven who received no study medication . All included patients were followed up for 26 weeks after treatment . FINDINGS 49 ( 36 % ) of 136 patients assigned monotherapy and 46 ( 35 % ) of 130 assigned combination therapy had lost HBeAg at the end of follow-up ( p=0.91 ) . More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment ( 57 [ 44 % ] vs 40 [ 29 % ] ; p=0.01 ) but relapsed during follow-up . Patterns were similar when response was assessed by suppression of serum hepatitis B virus ( HBV ) DNA or change in concentrations of alanine aminotransferase . Response rates ( HBeAg loss ) varied by HBV genotype ( p=0.01 ) : A , 42 ( 47 % ) patients ; B , ten ( 44 % ) ; C , 11 ( 28 % ) ; and D , 26 ( 25 % ) . INTERPRETATION Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy . HBV genotype is an important predictor of response to treatment The aim of this study was to investigate the efficacy of sequential use of telbivudine in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients with partial responses to pegylated interferon . Patients with partial responses to 48 weeks of pegylated interferon treatment were divided into two groups . In group A , patients stopped pegylated interferon directly without sequential treatment . In group B , patients received sequential treatment with telbivudine 600 mg/day . HBeAg , HBeAb , hepatitis B virus ( HBV ) DNA , alanine aminotransferase ( ALT ) and creatine kinase levels were determined at baseline and at weeks 12 , 24 , 36 and 48 . Responses and safety were assessed after 48 weeks of telbivudine treatment . Thirty-six patients were recruited . Eighteen of these patients stopped pegylated interferon without sequential treatment ( group A ) . After 48 weeks of follow-up , five patients ( 28 % ) had undergone HBeAg seroconversion , nine patients ( 50 % ) had undetectable levels of HBV DNA , and 11 patients ( 61 % ) achieved normal alanine aminotransferase ( ALT ) levels . The other 18 patients received sequential telbivudine treatment ( group B ) . After 48 weeks of treatment , 11 patients ( 61 % ) had undergone HBeAg seroconversion , and all patients had undetectable levels of HBV DNA and normal ALT levels . All patients tolerated sequential telbivudine treatment , and only slightly elevated creatine kinase levels were observed . Switching to telbivudine therapy was efficient and safe in HBeAg-positive chronic hepatitis B patients with partial responses to 48 weeks of pegylated interferon . Sequential treatment with telbivudine result ed in an HBeAg seroconversion rate of 61 % and an HBV DNA loss rate of 100 % after 48 weeks . This promising strategy warrants further investigation Lamivudine is a potent inhibitor of hepatitis B virus ( HBV ) replication , but its long-term use may be associated with HBV tyrosine-methionine-aspartate-aspartate ( YMDD ) motif mutation . To examine the clinical features and course after emergence of YMDD mutants , 55 patients who received lamivudine therapy over 104 weeks at our unit were assayed for YMDD mutation(s ) . Thirty-two of them were found to have the YMDD mutation . They continued lamivudine therapy and were followed up weekly or biweekly if clinical ly indicated . Thirty ( 93.7 % ) of them showed elevation of alanine transaminase ( ALT ) , and 13 ( 40.6 % ) experienced acute exacerbation at 4 to 94 weeks ( median , 24 weeks ) after emergence of the YMDD mutant . The incidence of exacerbation is much higher than 4.3 % in patients without the YMDD mutation ( P = .003 ) . Compared with patients without exacerbation , patients with exacerbation had a significantly higher serum HBV-DNA level after emergence of the YMDD mutant ( P < .005 ) . Before exacerbation , serum HBV-DNA level was rising to its peak , followed by the peaking of ALT ( 247 - 2,010 U/L ) 1 to 4 weeks later . Three patients developed hepatic decompensation , but then in association with hepatitis B e antigen ( HBeAg ) seroconversion , recovered . Of the 12 evaluable patients , 8 ( 75 % ) showed HBeAg seroconversion , and 3 showed mutant clearance within 1 to 5 months after exacerbation . In contrast , none of the patients without exacerbation showed HBeAg seroconversion ( P < .001 ) . These results indicate that acute exacerbations may occur after emergence of the YMDD mutation . The incidence , clinicopathological features , and subsequent course , and possibly the underlying immune mechanisms , are similar to those of wild-type HBV chronic infection . Because severe hepatitis may occur , patients should be followed carefully once the YMDD mutant emerges To assess whether extended treatment with interferon improves the outcome of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B , 101 consecutive patients were treated with 6 MU of interferon alfa 2b 3 times weekly for 24 months . During the 68-month study , 30 patients ( 30 % ) had a sustained response ( i.e. , normal serum transaminase levels and undetectable hepatitis B virus DNA by non-polymerase chain reaction [ PCR ] assays ) , and 15 cleared serum surface antigen . Twenty-five nonresponders , 16 relapsers , and 30 who discontinued treatment were considered treatment failures . Multivariate analysis predicted a sustained response for young age ( odds ratio , 0.94 ; 95 % confidence interval , 0.89 - 0.99 ; P = .041 ) and high pretreatment serum levels of immunoglobulin M ( IgM ) anti-hepatitis B core antigen ( HBc ) ( odds ratio , 4.52 ; 95 % confidence interval , 1.63 - 12.5 ; P = .004 ) . Liver disease progressed in none of the sustained responders but in 16 with treatment failure ( 0 % vs. 22 % , P = .002 ) ; hepatocellular carcinoma ( HCC ) developed with similar frequency in both groups ( 7 % ) . Overall , estimated 8-year complication-free survival was longer for the 30 sustained responders than the 71 patients with treatment failure ( 90 % vs. 60 % , P < .001 ) , but 8-year patient survival was similar in the 2 groups ( 100 % and 90 % ) . Short complication-free survival was predicted by failure to respond to interferon ( hazard ratio , 7.8 ; 95 % confidence interval , 1.8 - 34.0 ; P = .006 ) and high scores for liver fibrosis ( hazard ratio , 1.71 ; 95 % confidence interval , 1.17 - 2.50 ; P = .005 ) . In conclusion , 24 months of treatment with interferon alfa 2b led to sustained disease suppression in a significant proportion of patients with HBeAg-negative chronic hepatitis BACKGROUND / AIMS Monotherapy with pegylated interferon alpha ( Peg-IFNa ) or adefovir dipivoxil ( ADV ) to HBeAg-positive chronic hepatitis B ( CHB ) patients has limited effects . This study aims to evaluate therapeutic efficacy and safety of individualized combination therapy with Peg-IFNa and ADV . METHODOLOGY HBeAg-positive CHB patients ( n=160 ) were enrolled in this multi-center , prospect i ve , r and omized , ' real-life ' cohort study , of which received Peg IFNa-2a monotherapy or combination therapy with ADV base on the baseline features and treatment response . RESULTS At week 24 , percentages of ALT normalization , HBV DNA undetectable were both higher in individualized treatment group ( ITG , 57.50 % , 43.75 % ) than that in st and ard treatment group ( STG , 40.00 % , 27.50 % ; p=0.027 , 0.032 ) . The superiority of HBeAg clearance and seroconversion rates in ITG maintained from treatment termination ( 63.75 % , 56.25 % ) to 48 weeks follow-up ( 57.50 % , 53.75 % ) . At week 96 the combined response rates were 46.25 % in ITG compared with 30.00 % in STG ( p=0.034 ) . Furthermore , there was no statistically significant difference in relapse rates and adverse events between the two groups . CONCLUSIONS Individualized combination therapy can achieve higher antiviral response rates . In particular , it can accelerate undetectable HBV DNA and elevate HBeAg clearance/seroconversion rates to a greater degree than Peg-IFNa-2a monotherapy Aims The hepatitis B e antigen ( HBeAg ) seroconversion rate in HBeAg-positive chronic hepatitis B patients treated with peginterferon-&agr;2a ( peg-IFN & agr;2a ) is still low ( about 30 % ) . The aim of this study was to find a new combination therapy of peg-IFN & agr;2a with lamivudine to improve the efficacy in HBeAg-positive chronic hepatitis B patients . Patients and methods All patients started with peg-IFN & agr;2a treatment at a dose of 135 & mgr;g/week . If the concentration of hepatitis B virus ( HBV ) DNA was greater than 1.0 × 104 copies/ml and if the patient was positive for HBeAg at 12 weeks of treatment , lamivudine was included into the treatment for 12 weeks . Thereafter , the patients continued on peg-IFN & agr;2a alone for the full 52-week treatment course . Results Thirty-two patients were recruited , and eight of them achieved HBV DNA concentrations of less than 1.0 × 104 copies/ml or HBeAg loss at 12 weeks of treatment when lamivudine was not administered ( group A ) . The other 24 patients received additional lamivudine , started from 12 weeks of treatment for 12 weeks ( group B ) . At the end of treatment ( EOT ) , in the peg-IFN & agr;2a monotherapy group ( group A ) , eight patients ( 100 % ) had HBV DNA loss , six patients ( 75 % ) achieved HBeAg seroconversion , and eight patients ( 100 % ) achieved alanine aminotransferase ( ALT ) normalization . This level of response was sustained for 24 weeks after treatment in all patients with an early response . In the peg-IFN & agr;2a combined short-term lamivudine group ( group B ) , 12 patients ( 50 % ) had HBV DNA loss , nine patients ( 38 % ) achieved HBeAg seroconversion , one patient ( 4 % ) achieved hepatitis B surface antigen loss , and 15 patients ( 63 % ) achieved ALT normalization at EOT . One patient had an HBV DNA rebound and an HBeAg reversion 24 weeks after treatment . The total HBV DNA loss rate , HBeAg seroconversion rate , hepatitis B surface antigen loss rate , and ALT normalization rate in all patients were 59 , 47 , 3 , and 69 % , respectively , at EOT and were 56 , 44 , 3 , and 69 % 24 weeks after treatment , respectively . Conclusion This study indicates that the response-guided approach result ed in an overall HBeAg seroconversion rate of 47 % at EOT and 44 % 24 weeks after treatment . This promising strategy to increase response rates with peg-IFN & agr;2a warrants further investigation BACKGROUND Available treatments for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B are associated with poor sustained responses . As a result , nucleoside and nucleotide analogues are typically continued indefinitely , a strategy associated with the risk of resistance and unknown long-term safety implication s. METHODS We compared the efficacy and safety of peginterferon alfa-2a ( 180 microg once weekly ) plus placebo , peginterferon alfa-2a plus lamivudine ( 100 mg daily ) , and lamivudine alone in 177 , 179 , and 181 patients with HBeAg-negative chronic hepatitis B , respectively . Patients were treated for 48 weeks and followed for an additional 24 weeks . RESULTS After 24 weeks of follow-up , the percentage of patients with normalization of alanine aminotransferase levels or hepatitis B virus ( HBV ) DNA levels below 20,000 copies per milliliter was significantly higher with peginterferon alfa-2a monotherapy ( 59 percent and 43 percent , respectively ) and peginterferon alfa-2a plus lamivudine ( 60 percent and 44 percent ) than with lamivudine monotherapy ( 44 percent , P=0.004 and P=0.003 , respectively ; and 29 percent , P=0.007 and P=0.003 , respectively ) . Rates of sustained suppression of HBV DNA to below 400 copies per milliliter were 19 percent with peginterferon alfa-2a monotherapy , 20 percent with combination therapy , and 7 percent with lamivudine alone ( P<0.001 for both comparisons with lamivudine alone ) . Loss of hepatitis B surface antigen occurred in 12 patients in the peginterferon groups , as compared with 0 patients in the group given lamivudine alone . Adverse events , including pyrexia , fatigue , myalgia , and headache , were less frequent with lamivudine monotherapy than with peginterferon alfa-2a monotherapy or combination therapy . CONCLUSIONS Patients with HBeAg-negative chronic hepatitis B had significantly higher rates of response , sustained for 24 weeks after the cessation of therapy , with peginterferon alfa-2a than with lamivudine . The addition of lamivudine to peginterferon alfa-2a did not improve post-therapy response rates BACKGROUND AND METHODS In preliminary trials , lamivudine , an oral nucleoside analogue , has shown promise for the treatment of chronic hepatitis B. We conducted a one-year , double-blind trial of lamivudine in 358 Chinese patients with chronic hepatitis B. The patients were r and omly assigned to receive 25 mg of lamivudine ( 142 patients ) , 100 mg of lamivudine ( 143 ) , or placebo ( 73 ) orally once daily . The patients underwent liver biopsies before entering the study and after completing the assigned treatment regimen . The primary end point was a reduction of at least two points in the Knodell necroinflammatory score . RESULTS Hepatic necroinflammatory activity improved by two points or more in 56 percent of the patients receiving 100 mg of lamivudine , 49 percent of those receiving 25 mg of lamivudine , and 25 percent of those receiving placebo ( P<0.001 and P=0.001 , respectively , for the comparisons of lamivudine treatment with placebo ) . Necroinflammatory activity worsened in 7 percent of the patients receiving 100 mg of lamivudine , 8 percent of those receiving 25 mg , and 26 percent of those receiving placebo . The 100-mg dose of lamivudine was associated with a reduced progression of fibrosis ( P=0.01 for the comparison with placebo ) and with the highest rate of hepatitis B e antigen ( HBeAg ) seroconversion ( loss of HBeAg , development of antibody to HBeAg , and undetectable HBV DNA ) ( 16 percent ) , the greatest suppression of HBV DNA ( 98 percent reduction at week 52 as compared with the base-line value ) , and the highest rate of sustained normalization of alanine aminotransferase levels ( 72 percent ) . Ninety-six percent of the patients completed the study . The incidence of adverse events was similar in all groups , and there were few serious events . CONCLUSIONS In a one-year study , lamivudine was associated with substantial histologic improvement in many patients with chronic hepatitis B. A daily dose of 100 mg was more effective than a daily dose of 25 mg BACKGROUND The efficacy of pegylated interferon alfa-2b alone or in combination with lamivudine for the treatment of patients with hepatitis B e antigen ( HBeAg ) negative ( - ) chronic hepatitis B ( CHB ) is understudied . MATERIAL / METHODS One hundred twenty-six patients with HBeAg(-)chronic hepatitis B received pegylated interferon alfa-2b > or = 1.5 micro g/kg/wk for 48 weeks . Ninety of those subjects were r and omly selected to receive concomitant treatment with lamivudine 100 mg/d . The co primary end points were the subjects ' virologic ( hepatitis B virus deoxyribonucleic acid [ HBV DNA ] < 60 IU/mL ) and biochemical ( normalization of alanine aminotransferase levels ) responses 24 weeks after treatment cessation . RESULTS The scores for necroinflammatory activity and fibrosis in patients r and omly assigned to receive monotherapy were statistically significantly lower than those in patients receiving combination therapy . HBV DNA levels were statistically significantly higher and alanine aminotransferase levels were statistically significantly lower in patients receiving monotherapy than in those receiving combination therapy . Virologic responses in the monotherapy and combination therapy groups were similar at weeks 48 and 72 ( 59.1 vs 42.9 % ) . The biochemical response at week 72 was also similar in the treatment groups . The results of multiple regression analysis showed that the virologic response at week 72 was independently correlated with the pegylated interferon alfa-2b dose and that the biochemical response was independently correlated with necroinflammatory activity , the pegylated interferon alfa-2b dose , and lamivudine therapy . CONCLUSIONS These data support the use of pegylated interferon alfa-2b in patients with HBeAg(- ) chronic hepatitis B ; however , the concomitant use of lamivudine produced no additional clinical benefit In a r and omized , controlled trial of recombinant interferon alfa-2b with or without prednisone priming in Chinese adults with chronic hepatitis B virus infection , stratified r and omization for pretreatment serum alanine aminotransferase levels was done . Partial or complete antiviral responses were achieved in 17 ( 21.5 % ) of 79 treated patients and 3 ( 8.3 % ) of 36 controls ( P = 0.14 ) . The response to interferon treatment was significantly better in those who had elevated pretreatment transaminase levels and comparable to that reported in white patients [ 15 ( 38.5 % ) of 39 patients compared with 2 ( 5 % ) of 40 who had normal pretreatment transaminase levels ( P = 0.0005 ) ] . The spontaneous seroconversion rate was also higher among the controls with elevated transaminase levels [ 3 ( 18.8 % ) of 16 compared with 0 of 20 with normal transaminase levels ] , but this difference was not statistically significant ( P = 0.16 ) . Among the interferon-treated patients , prednisone priming appeared to have a marginal benefit over treatment with interferon alone in patients with elevated transaminase levels ( 43 % vs. 33 % ) , but not in those with normal transaminase levels ( 0 % vs. 9.5 % ) . It was confirmed that Chinese patients with normal transaminase levels respond very poorly to interferon alfa therapy . However , the response was significantly better in patients with elevated transaminase levels BACKGROUND Cost and clinical ly significant adverse effects are the major limiting factors of interferon ( IFN ) use in therapy for chronic hepatitis B virus ( HBV ) infection . A clinical trial was conducted in China to study the efficiency and clinical relevance of low-dose regimen of IFN treatment for chronic HBV infection and to reveal factors predicting sustained combined response . METHODS During a r and omized , open-label control study , hepatitis B e antigen (HBeAg)-positive patients with chronic HBV infection ( n=230 ) were assigned to receive pegylated IFN- alpha -2b ( 1.0 micro g/kg ) ( n=115 ) or IFN- alpha -2b ( 3 MIU ; n=115 ) for a 24-week period . Sustained combined response was assessed 24 weeks after the completion of treatment . RESULTS The greater rate of HBeAg loss in the pegylated IFN-group ( 23 % ) was the only statistically significant difference between the 2 treatment arms observed at the end of follow-up . The results of the multivariate statistical analysis revealed that HBV genotype B and patient age ( < or = 25 years ) were 2 independent factors associated with sustained combined response . A total of 40 % of patients with HBV genotype B aged < or = 25-years achieved sustained combined response . Only 4 ( 1.7 % ) of 230 patients discontinued therapy because of clinical ly significant adverse effects . CONCLUSIONS The choice of low-dose IFN regimen might be a relevant clinical option to reduce the cost and adverse effects of therapy for younger patients with chronic HBV infection and genotype B infection in countries where it is prevalent |
2,222 | 22,038,945 | Evidence indicates that capsaicin and capsiate both augment energy expenditure and enhance fat oxidation , especially at high doses .
Furthermore , the balance of the literature suggests that capsaicin and capsiate suppress orexigenic sensations .
The magnitude of these effects is small .
Purpose ful inclusion of these compounds in the diet may aid weight management , albeit modestly | Consumption of spicy foods containing capsaicin , the major pungent principle in hot peppers , reportedly promotes negative energy balance .
However , many individuals abstain from spicy foods due to the sensory burn and pain elicited by the capsaicin molecule .
A potential alternative for nonusers of spicy foods who wish to exploit this energy balance property is consumption of nonpungent peppers rich in capsiate , a recently identified nonpungent capsaicin analog contained in CH-19 Sweet peppers .
Capsiate activates transient receptor potential vanilloid subtype 1 ( TRPV1 ) receptors in the gut but not in the oral cavity .
This paper critically evaluates current knowledge on the thermogenic and appetitive effects of capsaicin and capsiate from foods and in supplemental form . | Two studies were conducted to investigate the effects of red pepper ( capsaicin ) on feeding behaviour and energy intake . In the first study , the effects of dietary red pepper added to high-fat ( HF ) and high-carbohydrate ( HC ) meals on subsequent energy and macronutrient intakes were examined in thirteen Japanese female subjects . After the ingestion of a st and ardized dinner on the previous evening , the subjects ate an experimental breakfast ( 1883 kJ ) of one of the following four types : ( 1 ) HF ; ( 2 ) HF and red pepper ( 10 g ) ; ( 3 ) HC ; ( 4 ) HC and red pepper . Ad libitum energy and macronutrient intakes were measured at lunch-time . The HC breakfast significantly reduced the desire to eat and hunger after breakfast . The addition of red pepper to the HC breakfast also significantly decreased the desire to eat and hunger before lunch . Differences in diet composition at breakfast time did not affect energy and macronutrient intakes at lunch-time . However , the addition of red pepper to the breakfast significantly decreased protein and fat intakes at lunch-time . In Study 2 , the effects of a red-pepper appetizer on subsequent energy and macronutrient intakes were examined in ten Caucasian male subjects . After ingesting a st and ardized breakfast , the subjects took an experimental appetizer ( 644 kJ ) at lunch-time of one of the following two types : ( 1 ) mixed diet and appetizer ; ( 2 ) mixed diet and red-pepper ( 6 g ) appetizer . The addition of red pepper to the appetizer significantly reduced the cumulative ad libitum energy and carbohydrate intakes during the rest of the lunch and in the snack served several hours later . Moreover , the power spectral analysis of heart rate revealed that this effect of red pepper was associated with an increase in the ratio sympathetic : parasympathetic nervous system activity . These results indicate that the ingestion of red pepper decreases appetite and subsequent protein and fat intakes in Japanese females and energy intake in Caucasian males . Moreover , this effect might be related to an increase in sympathetic nervous system activity in Caucasian males Objective : Bioactive food ingredients influence energy balance by exerting weak thermogenic effects . We studied whether the thermogenic effect of a combination of capsaicin , green tea extract ( catechins and caffeine ) , tyrosine , and calcium was maintained after 7-day treatment and whether local effects in the gastric mucosa were involved in the efficacy . Design : The present study was design ed as a 3-way crossover , r and omised , placebo-controlled , double-blinded intervention . Setting : Department of Human Nutrition , RVAU , Denmark . Subjects : A total of 19 overweight to obese men ( BMI : 28.0±2.7 kg/m2 ) were recruited by advertising locally . Intervention : The subjects took the supplements for a period of 7 days . The supplements were administrated as a simple supplement with the bioactive ingredients , a similar enterocoated version , or placebo . In all , 24-h energy expenditure ( EE ) , substrate oxidations , spontaneous physical activity ( SPA ) , and heart rate were measured in respiration chambers on the seventh day of each test period . Results : After adjustment for changes in body weight and SPA , 24-h EE was increased by 160 kJ/day ( 95 % CI : 15–305 ) by the simple preparation as compared to placebo , whereas the enterocoated preparation had no such effect ( 53 kJ/day , −92 to 198 ) ; simple vs enterocoated versions ( P=0.09 ) . The simple preparation produced a deficit in 24-h energy balance of 193 kJ/day ( 49–338 , P=0.03 ) . Fat and carbohydrate oxidation were equally increased by the supplements . Conclusion : A supplement containing bioactive food ingredients increased daily EE by ∼200 kJ or 2 % , without raising the heart rate or any observed adverse effects . The lack of effect of the enterocoated preparation suggests that a local action of capsaicin in the gastric mucosa is a prerequisite for exerting the thermogenic effect . Sponsorship : Supported by Science , Toxicology & Technology , San Francisco , CA , USA The aim of the present study was to investigate whether capsaicin assists weight maintenance by limiting weight regain after weight loss of 5 to 10 % . In this r and omized double-blind placebo-controlled study , ninety-one moderately overweight subjects were r and omly assigned to an intensive group that underwent all the measurements , and an extensive group that underwent the same measurements except the metabolism measurements . After a 4-week very-low-energy diet ( VLED ) intervention , a 3-month weight-maintenance period followed . During weight maintenance , subjects were divided into a capsaicin ( 135 mg capsaicin/d ) and a placebo group . Body mass was measured before and after the VLED and after 1 , 2 and 3 months of weight maintenance . The mean body-mass loss during the VLED was 6.6 ( SD 2.0 ) kg ( 7.8 ( SD 1.8 ) % initial body mass ) , and was not different between the subsequent treatment and placebo group . During weight maintenance , mean % regain during treatment was not significantly different compared with placebo ( 33.3 ( SD 35.7 ) v. 19.2 ( SD 41.8 ) % , P=0.09 ) . RQ was significantly less increased during weight maintenance in the treatment group compared with placebo ( 0.04 ( SD 0.06 ) v. 0.07 ( SD 0.05 ) , P<0.05 ) , indicating a relatively more sustained fat oxidation . Fat oxidation ( g/h ) after weight maintenance was higher in the capsaicin group compared with placebo ( 4.2 ( SD 1.1 ) v. 3.5 ( SD 0.9 ) , P<0.05 ) . These results indicate that capsaicin treatment caused sustained fat oxidation during weight maintenance compared with placebo . However , capsaicin treatment has no limiting effect on 3-month weight regain after modest weight loss Background Dihydrocapsiate ( DCT ) is a natural safe food ingredient which is structurally related to capsaicin from chili pepper and is found in the non-pungent pepper strain , CH-19 Sweet . It has been shown to elicit the thermogenic effects of capsaicin but without its gastrointestinal side effects . Methods The present study was design ed to examine the effects of DCT on both adaptive thermogenesis as the result of caloric restriction with a high protein very low calorie diet ( VLCD ) and to determine whether DCT would increase post-pr and ial energy expenditure ( PPEE ) in response to a 400 kcal/60 g protein liquid test meal . Thirty-three subjects completed an outpatient very low calorie diet ( 800 kcal/day providing 120 g/day protein ) over 4 weeks and were r and omly assigned to receive either DCT capsules three times per day ( 3 mg or 9 mg ) or placebo . At baseline and 4 weeks , fasting basal metabolic rate and PPEE were measured in a metabolic hood and fat free mass ( FFM ) determined using displacement plethysmography ( BOD POD ) . Results PPEE normalized to FFM was increased significantly in subjects receiving 9 mg/day DCT by comparison to placebo ( p < 0.05 ) , but decreases in resting metabolic rate were not affected . Respiratory quotient ( RQ ) increased by 0.04 in the placebo group ( p < 0.05 ) at end of the 4 weeks , but did not change in groups receiving DCT . Conclusions These data provide evidence for postpr and ial increases in thermogenesis and fat oxidation secondary to administration of dihydrocapsiate . Trial registration clinical Dietary red pepper suppresses energy intake and modifies macronutrient intake . We have investigated whether a stimulus in the mouth and the sensation of spiciness are necessary for red pepper-induced changes in energy and macronutrient intake in human volunteers . In a preliminary test , sixteen Japanese male volunteers tasted sample s of a soup with grade d doses of red pepper in order to define a moderate and a maximum tolerable ( strong ) dose of red pepper . On the day of the experiment , a st and ardised breakfast was given to the volunteers . At lunchtime , the subjects ingested one of four experimental soups containing either a placebo , a moderate or a strong dose of red pepper plus placebo capsules , or a placebo soup plus capsules delivering a strong dose of red pepper . The rest of the meal was given ad libitum to all subjects . The amount of food , protein and carbohydrate ingested was similar for all conditions . Energy and fat intake were similar after the ingestion of the moderate soup compared with placebo . However , the strong soup significantly lowered fat intake compared with placebo ( P=0.043 ) , and ingestion of strong capsules also tended to suppress it ( P=0.080 ) . Moreover , energy intake after strong soup and capsules tended to be lower than placebo ( P=0.089 and 0.076 , respectively ) . The present results indicate that the maximum tolerable dose is necessary to have a suppressive effect of red pepper on fat intake . The main site of the action of red pepper is not in the mouth BACKGROUND : Decreased appetite and increased energy expenditure after oral consumption of red pepper has been shown . OBJECTIVE : The aim of the present study was to assess the relative oral and gastrointestinal contribution to capsaicin-induced satiety and its effects on food intake or macronutrient selection . METHODS : For 24 subjects ( 12 men and 12 women ; age : 35±10 y ; BMI : 25.0±2.4 kg/m2 ; range 20–30 ) , 16 h food intake was assessed four times during 2 consecutive days by offering macronutrient-specific buffets and boxes with snacks , in our laboratory restaurant . At 30 min before each meal , 0.9 g red pepper ( 0.25 % capsaicin ; 80 000 Scoville Thermal Units ) or a placebo was offered in either tomato juice or in two capsules that were swallowed with tomato juice . Hunger and satiety were recorded using Visual Analogue Scales . RESULTS : Average daily energy intake in the placebo condition was 11.5±1.0 MJ/d for the men and 9.4±0.8 MJ/d for the women . After capsaicin capsules , energy intake was 10.4±0.6 and 8.3±0.5 MJ/d ( P<0.01 ) ; after capsaicin in tomato juice , it was 9.9±0.7 and 7.9±0.5 MJ/d , respectively ( compared to placebo : P<0.001 ; compared to capsaicin in capsules : P<0.05 ) . En % from carbohydrate/protein/fat ( C/P/F ) : changed from 46±3/15±1/39±2 to 52±4/15±1/33±2 en% ( P<0.01 ) in the men , and from 48±4/14±2/38±3 to 42±4/14±2/32±3 en% ( P<0.01 ) in the women , in both capsaicin conditions . Satiety ( area under the curve ) increased from 689 to 757 mmh in the men and from 712 to 806 mmh in the women , both ( P<0.01 ) . Only in the oral exposure condition was the reduction in energy intake and the increase in satiety related to perceived spiciness . CONCLUSION : In the short term , both oral and gastrointestinal exposure to capsaicin increased satiety and reduced energy and fat intake ; the stronger reduction with oral exposure suggests a sensory effect of capsaicin The biochemical and physiological indices were monitored in 44 subjects after 4-week capsinoids ( capsaicin analogues with low pungency ) intake . The subjects were r and omly assigned to 3 groups : CSNs3 ( 3 mg/kg of capsinoids ) , CSNs10 ( 10 mg/kg of capsinoids ) and the control ( placebo ) . Measurements were performed in the morning on overnight-fasted subjects . The oxygen consumption ( VO2 ) , resting energy expenditure ( REE ) and fat oxidation increased slightly compared to pre-administration values without any adverse effects , although the increase was not significant . The increase in fat oxidation was positively and significantly correlated with the body mass index ( BMI ) . A meta- analysis was therefore conducted on a subgroup consisting of subjects with BMI ≥ 25 ( n=28 ) . As a result , not only VO2 increased significantly ( p<0.05 ) in the CSNs10 group , but also REE in the CSNs10 group and fat oxidation in the CSNs3 and CSNs10 groups tended to increase ( p<0.1 ) . Consequently , a capsinoids intake would be able to enhance the energy expenditure and fat burning in humans , particularly those with high BMI The experiments reported here found that judgments of ' burn ' intensity are affected by long-term memory ( LTM ) . The implication of these findings for range-frequency theory and the role of LTM in intensity judgments are discussed OBJECTIVE : To describe the design , methods , and first year results of the Pound of Prevention ( POP ) study , a r and omized trial examining whether weight gain with age can be prevented using low intensity intervention . DESIGN : Participants were r and omized to either ( 1 ) no-contact control , ( 2 ) education through monthly newsletters and semiannual classes on nutrition and exercise , and ( 3 ) education plus a lottery incentive for participation . SUBJECTS : Two hundred and twenty-eight men , 594 high-income women , and 404 low-income women . Entry requirements were age 20–45 y , healthy , and willing to participate for three years . MEASUREMENTS : At baseline and one year later , participants were weighed and completed question naires about behaviors and attitudes related to weight and weight control . RESULTS : Mean body mass indices at baseline were 28.1 , 26.1 , and 28.2 for men , high-income women and low-income women , respectively . After one year , participants in the intervention conditions reported significantly increased frequency of weight monitoring , but no change in other targeted behaviors . One year weight changes in the control , education , and education plus lottery groups were 1.94 lb , 0.72 lb , and 0.21 lb in men ; 1.38 lb , 1.03 lb , and 0.51 lb in high-income women ; and 1.30 lb , 2.11 lb , and 3.23 lb in low-income women . CONCLUSIONS : These one-year results suggest that the intervention may be having a greater impact on high than low-income participants BACKGROUND & AIMS Bioactive ingredients have been shown to reduce appetite and energy intake . The magnitude of these effects might depend on energy balance why it was investigated how capsaicin , green tea , CH-19 sweet pepper as well as green tea and capsaicin affect appetite and energy intake during respectively negative and positive energy balance . METHODS 27 subjects were r and omized to three weeks of negative and three weeks of positive energy balance during which capsaicin , green tea , CH-19 sweet pepper , capsaicin+green tea or placebo was ingested on ten separate test days while the effects on appetite , energy intake , body weight and heart rate were assessed . RESULTS CH-19 sweet pepper and a combination of capsaicin and green tea reduced energy intake during positive energy balance . Capsaicin and green tea suppressed hunger and increased satiety more during negative than during positive energy balance . CONCLUSIONS Bioactive ingredients had energy intake reducing effects when used in combinations and in positive energy balance . Energy balance did not affect possible treatment induced energy intake , but did affect appetite by supporting negative energy balance . Bioactive ingredients may therefore be helpful in reducing energy intake and might support weight loss periods by relatively sustaining satiety and suppressing hunger The effects of dietary hot red pepper on energy metabolism at rest and during exercise were examined in long distance male runners 18 - 23 yr of age . A st and ardized meal was given on the evening prior to the experiment . The subjects had a meal ( 2720 kJ ) with or without 10 g of hot red pepper for breakfast . During rest ( 2.5 h after meal ) and exercise ( pedaling for 1 h at 150 W , about 60 % VO2max , using cycling ergometry ) , expired gasses and venous blood were collected . The meal with hot red pepper significantly elevated respiratory quotient and blood lactate levels at rest and during exercise . Oxygen consumption at rest was slightly but nonsignificantly higher in the hot red pepper meal at 30 min after the meal . Plasma epinephrine and norepinephrine levels were significantly higher in those who had only hot red pepper at 30 min after the meal . These results suggest that hot red pepper ingestion stimulates carbohydrate oxidation at rest and during exercise Previous studies suggest consumption of red pepper ( RP ) promotes negative energy balance . However , the RP dose provided in these studies ( up to 10 g/meal ) usually exceeded the amount preferred by the general population in the United States ( mean=~1 g/meal ) . The objective of this study was to evaluate the effects of hedonically acceptable RP doses served at a single meal in healthy , lean individuals on thermogenesis and appetite . Twenty-five men and women ( aged 23.0 ± 0.5 years , BMI 22.6 ± 0.3 kg/m(2 ) , 13 spicy food users and 12 non-users ) participated in a r and omized crossover trial during which they consumed a st and ardized quantity ( 1 g ) ; their preferred quantity ( regular spicy food users 1.8 ± 0.3 g/meal , non-users 0.3 ± 0.1 g/meal ) ; or no RP . Energy expenditure , core body and skin temperature , and appetite were measured . Postpr and ial energy expenditure and core body temperature were greater , and skin temperature was lower , after test loads with 1 g RP than no RP . Respiratory quotient was lower after the preferred RP dose was ingested orally , compared to in capsule form . These findings suggest that RP 's effects on energy balance stem from a combination of metabolic and sensory inputs , and that oral exposure is necessary to achieve RP 's maximum benefits . Energy intake was lower after test loads with 1 g RP than no RP in non-users , but not in users . Preoccupation with food , and the desire to consume fatty , salty , and sweet foods were decreased more ( or tended to be decreased more ) in non-users than users after a 1 g RP test load , but did not vary after a test load with no RP . This suggests that individuals may become desensitized to the effects of RP with long-term spicy food intake In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies |
2,223 | 21,949,226 | They also showed that CVD events increased linearly , with no threshold , along with 2-h postmeal plasma glucose levels ( 7,8 ) .
In this issue of Diabetes Care , Cavalot et al. ( 10 ) add further evidence of the harmful relationship between postmeal glucose levels and | Postpr and ial glucose ( PPG ) has a noxious effect on the vascular endothelium , which is mainly mediated by oxidative stress .
This condition leads to endothelial activation and dysfunction , two prerequisites for the onset of cardiovascular disease ( CVD ) ( 1 ) .
The importance of PPG is reflected in the creation of guidelines by the International Diabetes Federation ( IDF ) for the management of postmeal glucose ( http://www.idf.org/ guidelines /postmeal-glucose ) .
The relationship between postchallenge hyperglycemia and CVD has been addressed by several studies .
In the Honolulu Heart Program , the risk of coronary heart disease was increased in Japanese American men aged 45–68 years who had an abnormal oral glucose tolerance test ( 2 ) . | CONTEXT The worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns . OBJECTIVE To evaluate the effect of decreasing postpr and ial hyperglycemia with acarbose , an alpha-glucosidase inhibitor , on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance ( IGT ) . DESIGN , SETTING , AND PARTICIPANTS International , multicenter double-blind , placebo-controlled , r and omized trial , undertaken in hospitals in Canada , Germany , Austria , Norway , Denmark , Sweden , Finl and , Israel , and Spain from July 1998 through August 2001 . A total of 1429 patients with IGT were r and omized with 61 patients ( 4 % ) excluded because they did not have IGT or had no postr and omization data , leaving 1368 patients for a modified intent-to-treat analysis . Both men ( 49 % ) and women ( 51 % ) participated with a mean ( SD ) age of 54.5 ( 7.9 ) years and body mass index of 30.9 ( 4.2 ) . These patients were followed up for a mean ( SD ) of 3.3 ( 1.2 ) years . INTERVENTION Patients with IGT were r and omized to receive either placebo ( n = 715 ) or 100 mg of acarbose 3 times a day ( n = 714 ) . MAIN OUTCOME MEASURES The development of major cardiovascular events ( coronary heart disease , cardiovascular death , congestive heart failure , cerebrovascular event , and peripheral vascular disease ) and hypertension ( > or = 140/90 mm Hg ) . RESULTS Three hundred forty-one patients ( 24 % ) discontinued their participation prematurely , 211 in the acarbose-treated group and 130 in the placebo group ; these patients were also followed up for outcome parameters . Decreasing postpr and ial hyperglycemia with acarbose was associated with a 49 % relative risk reduction in the development of cardiovascular events ( hazard ratio [ HR ] , 0.51 ; 95 % confidence interval [ CI ] ; 0.28 - 0.95 ; P = .03 ) and a 2.5 % absolute risk reduction . Among cardiovascular events , the major reduction was in the risk of myocardial infa rct ion ( HR , 0.09 ; 95 % CI , 0.01 - 0.72 ; P = .02 ) . Acarbose was also associated with a 34 % relative risk reduction in the incidence of new cases of hypertension ( HR , 0.66 ; 95 % CI , 0.49 - 0.89 ; P = .006 ) and a 5.3 % absolute risk reduction . Even after adjusting for major risk factors , the reduction in the risk of cardiovascular events ( HR , 0.47 ; 95 % CI , 0.24 - 0.90 ; P = .02 ) and hypertension ( HR , 0.62 ; 95 % CI , 0.45 - 0.86 ; P = .004 ) associated with acarbose treatment was still statistically significant . CONCLUSION This study suggests that treating IGT patients with acarbose is associated with a significant reduction in the risk of cardiovascular disease and hypertension OBJECTIVE —Hyperglycemia and Its Effect After Acute Myocardial Infa rct ion on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus ( HEART2D ) is a multinational , r and omized , controlled trial design ed to compare the effects of pr and ial versus fasting glycemic control on risk for cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infa rct ion ( AMI ) . RESEARCH DESIGN AND METHODS — Patients ( type 2 diabetes , aged 30–75 years ) were r and omly assigned within 21 days after AMI to the 1 ) pr and ial strategy ( PR AND IAL ) ( three premeal doses of insulin lispro targeting 2-h postpr and ial blood glucose < 7.5 mmol/l ) or the 2 ) basal strategy ( BASAL ) ( NPH twice daily or insulin glargine once daily targeting fasting/premeal blood glucose < 6.7 mmol/l ) . RESULTS —A total of 1,115 patients were r and omly assigned ( PR AND IAL n = 557 ; BASAL n = 558 ) , and the mean patient participation after r and omization was 963 days ( range 1–1,687 days ) . The trial was stopped for lack of efficacy . Risks of first combined adjudicated primary cardiovascular events in the PR AND IAL ( n = 174 , 31.2 % ) and BASAL ( n = 181 , 32.4 % ) groups were similar ( hazard ratio 0.98 [ 95 % CI 0.8–1.21 ] ) . Mean A1C did not differ between the PR AND IAL and BASAL groups ( 7.7 ± 0.1 vs. 7.8 ± 0.1 % ; P = 0.4 ) during the study . The PR AND IAL group showed a lower daily mean postpr and ial blood glucose ( 7.8 vs. 8.6 mmol/l ; P < 0.01 ) and 2-h postpr and ial blood glucose excursion ( 0.1 vs. 1.3 mmol/l ; P < 0.001 ) versus the BASAL group . The BASAL group showed lower mean fasting blood glucose ( 7.0 vs. 8.1 mmol/l ; P < 0.001 ) and similar daily fasting/premeal blood glucose ( 7.7 vs. 7.3 mmol/l ; P = 0.233 ) versus the PR AND IAL group . CONCLUSIONS —Treating diabetic survivors of AMI with pr and ial versus basal strategies achieved differences in fasting blood glucose , less-than-expected differences in postpr and ial blood glucose , similar levels of A1C , and no difference in risk for future cardiovascular event rates BACKGROUND Improved blood-glucose control decreases the progression of diabetic microvascular disease , but the effect on macrovascular complications is unknown . There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation . We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a r and omised controlled trial . METHODS 3867 newly diagnosed patients with type 2 diabetes , median age 54 years ( IQR 48 - 60 years ) , who after 3 months ' diet treatment had a mean of two fasting plasma glucose ( FPG ) concentrations of 6.1 - 15.0 mmol/L were r and omly assigned intensive policy with a sulphonylurea ( chlorpropamide , glibenclamide , or glipizide ) or with insulin , or conventional policy with diet . The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group , the aim was the best achievable FPG with diet alone ; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment : any diabetes-related endpoint ( sudden death , death from hyperglycaemia or hypoglycaemia , fatal or non-fatal myocardial infa rct ion , angina , heart failure , stroke , renal failure , amputation [ of at least one digit ] , vitreous haemorrhage , retinopathy requiring photocoagulation , blindness in one eye , or cataract extraction ) ; diabetes-related death ( death from myocardial infa rct ion , stroke , peripheral vascular disease , renal disease , hyperglycaemia or hypoglycaemia , and sudden death ) ; all-cause mortality . Single clinical endpoints and surrogate sub clinical endpoints were also assessed . All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy . FINDINGS Over 10 years , haemoglobin A1c ( HbA1c ) was 7.0 % ( 6.2 - 8.2 ) in the intensive group compared with 7.9 % ( 6.9 - 8.8 ) in the conventional group -- an 11 % reduction . There was no difference in HbA1c among agents in the intensive group . Compared with the conventional group , the risk in the intensive group was 12 % lower ( 95 % CI 1 - 21 , p=0.029 ) for any diabetes-related endpoint ; 10 % lower ( -11 to 27 , p=0.34 ) for any diabetes-related death ; and 6 % lower ( -10 to 20 , p=0.44 ) for all-cause mortality . Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25 % risk reduction ( 7 - 40 , p=0.0099 ) in microvascular endpoints , including the need for retinal photocoagulation . There was no difference for any of the three aggregate endpoints between the three intensive agents ( chlorpropamide , glibenclamide , or insulin ) . Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis ( both p<0.0001 ) . The rates of major hypoglycaemic episodes per year were 0.7 % with conventional treatment , 1.0 % with chlorpropamide , 1.4 % with glibenclamide , and 1.8 % with insulin . Weight gain was significantly higher in the intensive group ( mean 2.9 kg ) than in the conventional group ( p<0.001 ) , and patients assigned insulin had a greater gain in weight ( 4.0 kg ) than those assigned chlorpropamide ( 2.6 kg ) or glibenclamide ( 1.7 kg ) . INTERPRETATION Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications , but not macrovascular disease , in patients with type 2 diabetes . ( ABSTRACT TRUNCATED CONTEXT The role of triglycerides in the risk of ischemic stroke remains controversial . Recently , a strong association was found between elevated levels of nonfasting triglycerides , which indicate the presence of remnant lipoproteins , and increased risk of ischemic heart disease . OBJECTIVE To test the hypothesis that increased levels of nonfasting triglycerides are associated with ischemic stroke in the general population . DESIGN , SETTING , AND PARTICIPANTS The Copenhagen City Heart Study , a prospect i ve , Danish population -based cohort study initiated in 1976 , with follow-up through July 2007 . Participants were 13,956 men and women aged 20 through 93 years . A cross-sectional study included 9637 individuals attending the 1991 - 1994 examination of the prospect i ve study . MAIN OUTCOME MEASURES Prospect i ve study : baseline levels of nonfasting triglycerides , other risk factors at baseline and at follow-up examinations , and incidence of ischemic stroke . Cross-sectional study : levels of nonfasting triglycerides , levels of remnant cholesterol , and prevalence of ischemic stroke . RESULTS Of the 13,956 participants in the prospect i ve study , 1529 developed ischemic stroke . Cumulative incidence of ischemic stroke increased with increasing levels of nonfasting triglycerides ( log-rank trend , P < .001 ) . Men with elevated nonfasting triglyceride levels of 89 through 176 mg/dL had multivariate-adjusted hazard ratios ( HRs ) for ischemic stroke of 1.3 ( 95 % CI , 0.8 - 1.9 ; 351 events ) ; for 177 through 265 mg/dL , 1.6 ( 95 % CI , 1.0 - 2.5 ; 189 events ) ; for 266 through 353 mg/dL , 1.5 ( 95 % CI , 0.9 - 2.7 ; 73 events ) ; for 354 through 442 mg/dL , 2.2 ( 95 % CI , 1.1 - 4.2 ; 40 events ) ; and for 443 mg/dL or greater , 2.5 ( 95 % CI , 1.3 - 4.8 ; 41 events ) vs men with nonfasting levels less than 89 mg/dL ( HR , 1.0 ; 85 events ) ( P < .001 for trend ) . Corresponding values for women were 1.3 ( 95 % CI , 0.9 - 1.7 ; 407 events ) , 2.0 ( 95 % CI , 1.3 - 2.9 ; 135 events ) , 1.4 ( 95 % CI , 0.7 - 2.9 ; 26 events ) , 2.5 ( 95 % CI , 1.0 - 6.4 ; 13 events ) , and 3.8 ( 95 % CI , 1.3 - 11 ; 10 events ) vs women with nonfasting triglyceride levels less than 89 mg/dL ( HR , 1.0 ; 159 events ) ( P < .001 for trend ) . Absolute 10-year risk of ischemic stroke ranged from 2.6 % in men younger than 55 years with nonfasting triglyceride levels of less than 89 mg/dL to 16.7 % in men aged 55 years or older with levels of 443 mg/dL or greater . Corresponding values in women were 1.9 % and 12.2 % . In the cross-sectional study , men with a previous ischemic stroke vs controls had nonfasting triglyceride levels of 191 ( IQR , 131 - 259 ) mg/dL vs 148 ( IQR , 104 - 214 ) mg/dL ( P < .01 ) ; corresponding values for women were 167 ( IQR , 121 - 229 ) mg/dL vs 127 ( IQR , 91 - 181 ) mg/dL ( P < .05 ) . For remnant cholesterol , corresponding values were 38 ( IQR , 26 - 51 ) mg/dL vs 29 ( IQR , 20 - 42 ) mg/dL in men ( P < .01 ) and 33 ( IQR , 24 - 45 ) mg/dL vs 25 ( IQR , 18 - 35 ) mg/dL in women ( P < .05 ) . CONCLUSION In this study population , nonfasting triglyceride levels were associated with risk of ischemic stroke OBJECTIVE Postpr and ial glycemia is an independent risk factor for cardiovascular disease that is more powerful than fasting glycemia and determines myocardial perfusion defects in type 2 diabetes . We examined the efficacy of two different insulin regimes ( regular insulin and insulin analog ) in controlling postpr and ial hyperglycemia and in preventing myocardial perfusion abnormalities . RESEARCH DESIGN AND METHODS A total of 20 consecutive type 2 diabetic patients and 20 control subjects were enrolled in this r and omized , three-way , cross-over , placebo-controlled study . Myocardial perfusion was assessed by myocardial contrast echocardiography ( MCE ) in fasting and postpr and ial ( 120 min ) state . RESULTS Insulin analog was associated with lower , but not statistically significant , postpr and ial glycemia than regular insulin ( glucose increase : 116 + /- 8 vs. 136 + /- 5 % , P = NS ) . However , the area under the curve following insulin analog was significantly lower than regular insulin ( 18,354 + /- 702 vs. 20,757 + /- 738 mg per 120 min , P = 0.032 ) . Fasting myocardial flow velocity ( beta ) , myocardial blood volume ( MBV ) , and myocardial blood flow ( MBF ) did not differ between control and type 2 diabetic subjects . Postpr and ial beta ( 0.67 + /- 0.24 vs. 0.92 + /- 0.25 , P < 0.01 ) , MBV ( 8.4 + /- 2 vs. 10.9 + /- 1.2 , P < 0.01 ) , and MBF ( 5.6 + /- 2 vs. 9.9 + /- 2.8 , P < 0.01 ) increased significantly in control subjects . In type 2 diabetes , during placebo in the postpr and ial state , beta increased ( 0.65 + /- 0.27 vs. 0.89 + /- 0.24 , P < 0.01 ) , while MBV ( 8.34 + /- 1.2 vs. 4.3 + /- 1.3 , P < 0.01 ) and MBF ( 5.4 + /- 1.5 vs. 3.4 + /- 0.9 , P < 0.01 ) decreased . Similar changes in MCE variables were observed after regular insulin : beta increased ( 0.65 + /- 0.22 vs. 0.92 + /- 0.12 , P < 0.01 ) and MBV ( 8.2 + /- 2 vs. 5.2 + /- 1.16 , P < 0.01 ) and MBF ( 5.4 + /- 1.9 vs. 4.2 + /- 0.86 , P < 0.01 ) were reduced . After insulin analog , postpr and ial beta ( 0.66 + /- 0.18 vs. 0.9 + /- 0.18 , P < 0.01 ) , MBV ( 8.2 + /- 1.6 vs. 9.6 + /- 1.2 , P < 0.01 ) , and MBF ( 5.4 + /- 2 vs. 7.2 + /- 1.9 , P < 0.01 ) increased . Values of postpr and ial MBV and MBF were higher after insulin analog than regular insulin treatment . CONCLUSIONS Insulin analog partially reversed myocardial perfusion abnormalities observed in postpr and ial state by improving glucose control Summary The Diabetes Intervention Study ( DIS ) is a prospect i ve population -based multicentre trial of newly detected cases of non-insulin-dependent diabetes mellitus ( NIDDM ) . This report analyses the risk factors for subsequent coronary heart disease and all-cause death during the 11-year follow-up . The prognostic significance of the categories of the NIDDM Policy Group was vali date d with respect to the incidence of coronary heart disease and mortality . At baseline 1139 subjects , aged 30–55 years at the time of diabetes detection and classified as diet controlled after a 6-week screening phase , were included . Of the patients 112 ( 15.2 % ) suffered from myocardial infa rct ion , 197 ( 19.82 % ) of 994 had died . The odds ratio for all-cause mortality compared to the general population for males at the age of 36–45 years was 5.1 and for females 7.0 . In multivariate analysis age , blood pressure and smoking were independent risk factors for myocardial infa rct ion and male sex , age , blood pressure , triglycerides , postpr and ial blood glucose and smoking for death , respectively . The categories of the NIDDM Policy Group target parameters for blood glucose , triglycerides and blood pressure were significant predictors of both CHD and death . Thus , it appears that in NIDDM good control of blood glucose , blood pressure and triglycerides is associated with a lower incidence of coronary heart disease and death rate respectively . [ Diabetologia ( 1996 ) 39 : 1577–1583 The aim of this study was to compare the acute effect of ( i ) meals rich in saturated fat , oleic acid , and alpha-linolenic acid and ( ii ) meals rich in starch and fiber on markers of inflammation and oxidative stress in obese and lean women . In a crossover study , 15 abdominally obese women ( age , 54 + /- 9 years ; BMI , 37.3 + /- 5.5 kg/m2 ) and 14 lean women ( age , 53 + /- 10 years ; BMI , 22.9 + /- 1.9 kg/m2 ) consumed meals rich in cream ( CR ) , olive oil ( OL ) , canola oil ( CAN ) , potato ( POT ) , and All-Bran ( BRAN ) in r and om order . Blood sample s were collected before and up to 6 h after the meals and plasma interleukin-6 ( IL-6 ) , IL-8 , tumor necrosis factor-alpha ( TNF-alpha ) , lipid peroxides ( LPOs ) , free-fatty acids ( FFAs ) , insulin , glucose , and cortisol were measured . Plasma IL-6 decreased significantly 1 h after the meals then increased significantly above baseline at 4h and 6h in obese women and at 6h in lean women . The incremental area under the curve ( iAUC ) for IL-6 was significantly ( P = 0.02 ) higher in obese compared with lean women and was significantly lower following the high fiber BRAN meal compared with a POT meal ( P = 0.003 ) . Waist circumference ( R = 0.491 , P = 0.007 ) and cortisol AUC ( R = -0.415 , P = 0.03 ) were significant determinants of the magnitude of 6h changes in plasma IL-6 after the meals . These findings suggest that the postpr and ial response of plasma IL-6 concentrations may be influenced by the type of carbohydrate in the meal , central adiposity , and circulating cortisol concentrations in women OBJECTIVE To determine whether there are thresholds for fasting and for 2-h glucose above which the risk of death from all causes and from coronary heart disease ( CHD ) increases . RESEARCH DESIGN AND METHODS We studied 23-year mortality data from the Paris Prospect i ve Study of the 7,018 men , aged 44 - 55 years , who were not known as diabetic at the baseline examination . The effect of glucose concentrations on mortality was studied using the observed relative risks and an age-adjusted Cox proportional hazards model . RESULTS For all causes of death , there were J-shaped relationships with both fasting and 2-h glucose concentrations , and the lowest observed death rates were in the intervals centered on 5.5 mmol/l for fasting glucose and 5.0 mmol/l for 2-h glucose . The death rates for CHD were low in this population : for fasting glucose , the hazards ratio was best modeled by a positive linear relationship ; for 2-h glucose , it was modeled by a J-shaped curve and the lowest observed death rate was in the interval centered on 6.0 mmol/l . CONCLUSIONS In the Paris Prospect i ve Study , there were no clear thresholds for fasting or 2-h glucose concentrations above which mortality sharply increased ; in the upper levels of the glucose distributions , the risk of death progressively increased with increasing fasting and 2-h glucose concentrations BACKGROUND The ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown . METHODS In a double-blind , r and omized clinical trial , we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide ( up to 60 mg three times daily ) or placebo , in a 2-by-2 factorial design with valsartan or placebo , in addition to participation in a lifestyle modification program . We followed the participants for a median of 5.0 years for incident diabetes ( and a median of 6.5 years for vital status ) . We evaluated the effect of nateglinide on the occurrence of three co primary outcomes : the development of diabetes ; a core cardiovascular outcome that was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , or hospitalization for heart failure ; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome , hospitalization for unstable angina , or arterial revascularization . RESULTS After adjustment for multiple testing , nateglinide , as compared with placebo , did not significantly reduce the cumulative incidence of diabetes ( 36 % and 34 % , respectively ; hazard ratio , 1.07 ; 95 % confidence interval [ CI ] , 1.00 to 1.15 ; P=0.05 ) , the core composite cardiovascular outcome ( 7.9 % and 8.3 % , respectively ; hazard ratio , 0.94 , 95 % CI , 0.82 to 1.09 ; P=0.43 ) , or the extended composite cardiovascular outcome ( 14.2 % and 15.2 % , respectively ; hazard ratio , 0.93 , 95 % CI , 0.83 to 1.03 ; P=0.16 ) . Nateglinide did , however , increase the risk of hypoglycemia . CONCLUSIONS Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors , assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the co primary composite cardiovascular outcomes . ( Clinical Trials.gov number , NCT00097786 . |
2,224 | 19,431,054 | Large effects were noted for patient satisfaction , while moderate effects were evident for patients ' quality of life and readmission rates . | In the present healthcare environment , budget cuts , staff shortages , and re source limitations are grave concerns .
The elderly in particular consume a considerable proportion of hospital re sources .
Thus , the discharge planner 's role , particularly with respect to elderly patients , is extremely important . | CONTEXT Comprehensive discharge planning by advanced practice nurses has demonstrated short-term reductions in readmissions of elderly patients , but the benefits of more intensive follow-up of hospitalized elders at risk for poor outcomes after discharge has not been studied . OBJECTIVE To examine the effectiveness of an advanced practice nurse-centered discharge planning and home follow-up intervention for elders at risk for hospital readmissions . DESIGN R and omized clinical trial with follow-up at 2 , 6 , 12 , and 24 weeks after index hospital discharge . SETTING Two urban , academically affiliated hospitals in Philadelphia , Pa. PARTICIPANTS Eligible patients were 65 years or older , hospitalized between August 1992 and March 1996 , and had 1 of several medical and surgical reasons for admission . INTERVENTION Intervention group patients received a comprehensive discharge planning and home follow-up protocol design ed specifically for elders at risk for poor outcomes after discharge and implemented by advanced practice nurses . MAIN OUTCOME MEASURES Readmissions , time to first readmission , acute care visits after discharge , costs , functional status , depression , and patient satisfaction . RESULTS A total of 363 patients ( 186 in the control group and 177 in the intervention group ) were enrolled in the study ; 70 % of intervention and 74 % of control subjects completed the trial . Mean age of sample was 75 years ; 50 % were men and 45 % were black . By week 24 after the index hospital discharge , control group patients were more likely than intervention group patients to be readmitted at least once ( 37.1 % vs 20.3 % ; P<.001 ) . Fewer intervention group patients had multiple readmissions ( 6.2 % vs 14.5 % ; P = .01 ) and the intervention group had fewer hospital days per patient ( 1.53 vs 4.09 days ; P<.001 ) . Time to first readmission was increased in the intervention group ( P<.001 ) . At 24 weeks after discharge , total Medicare reimbursements for health services were about $ 1.2 million in the control group vs about $ 0.6 million in the intervention group ( P<.001 ) . There were no significant group differences in post-discharge acute care visits , functional status , depression , or patient satisfaction . CONCLUSIONS An advanced practice nurse-centered discharge planning and home care intervention for at-risk hospitalized elders reduced readmissions , lengthened the time between discharge and readmission , and decreased the costs of providing health care . Thus , the intervention demonstrated great potential in promoting positive outcomes for hospitalized elders at high risk for rehospitalization while reducing costs BACKGROUND Few investigators have targeted elderly patients and monitored outcomes of care in studies on discharge planning interventions after critical illness . OBJECTIVES To pilot test an intensive care unit-based nursing screening intervention to assist in determining the discharge needs and outcomes of critically ill elderly patients . METHOD A r and omized clinical trial with in-hospital and mailed question naires was used . Patients 65 years and older who were hospitalized in 1 of 2 intensive care units at 2 midwestern university-affiliated medical centers were recruited for the study . Control patients ( n = 53 ) received usual discharge planning , experimental patients ( n = 47 ) were screened in the intensive care unit by using the Discharge Planning Question naire . Both groups were assessed for readiness for discharge when discharged from the hospital and were followed up 2 weeks later with a survey completed at home . RESULTS One hundred patients 65 to 90 years old ( mean 73 , SD 5.78 ) completed the study . Sixty-six percent were men . The 2 groups did not differ with regard to age , race , sex , severity of illness , lengths of stay in the intensive care unit or hospital , education level , or income . Patients in the experimental group were more ready than patients in the control group for discharge ( P = .06 ) . Patients in the experimental group were also more likely to report they had adequate information , had less concern about managing their care at home , knew their medicines , and knew danger signals indicating potential complications . CONCLUSION Intensive care unit-based early discharge planning can affect elderly patients ' preparation for discharge OBJECTIVES to investigate the effectiveness of a pharmacy discharge plan in elderly hospitalized patients . DESIGN r and omized controlled trial . SUBJECTS AND SETTING S we r and omized patients aged 75 years and older on four or more medicines who had been discharged from three acute general and one long-stay hospital to a pharmacy intervention or usual care . INTERVENTIONS the hospital pharmacist developed discharge plans which gave details of medication and support required by the patient . A copy was given to the patient and to all relevant professionals and carers . This was followed by a domiciliary assessment by a community pharmacist . In the control group , patients were discharged from hospital following st and ard procedures that included a discharge letter to the general practitioner listing current medications . OUTCOMES the primary outcome was re-admission to hospital within 6 months . Secondary outcomes included the number of deaths , attendance at hospital outpatient clinics and general practice and proportion of days in hospital over the follow-up period , together with patients ' general well-being , satisfaction with the service and knowledge of and adherence to prescribed medication . RESULTS we recruited 362 patients , of whom 181 were r and omized to each group . We collected hospital and general practice data on at least 91 and 72 % of patients respectively at each follow-up point and interviewed between 43 and 90 % of the study subjects . There were no significant differences between the groups in the proportion of patients re-admitted to hospital between baseline and 3 months or 3 and 6 months . There were no significant differences in any of the secondary outcomes . CONCLUSIONS we found no evidence to suggest that the co-ordinated hospital and community pharmacy care discharge plans in elderly patients in this study influence outcomes The evidence -based medicine ( EBM ) related concepts of hierarchy of evidence , meta-analyses , confidence intervals , study design , etc . are nowadays so widespread , that clinicians willing to use today 's medical literature with underst and ing have no choice but to become familiar with EBM principles and method ologies . Although surgeons may perceive that evidence -based medicine m and ates a strict adherence to r and omised trials , it more accurately involves informed and effective use of all types of evidence ( from meta- analysis of r and omised trials to individual case series and case reports . With the ever-increasing amount of available information , surgeons must consider a shift in paradigm from traditional practice to one that involves question formulation , validity assessment of available studies and appropriate application of research evidence to individual patients OBJECTIVE to prove the effectiveness of geriatric evaluation and management for elderly , hospitalized patients , combined with post-discharge home intervention by an interdisciplinary team . DESIGN r and omized controlled trial with outcome and costs assessed for 12 months after the date of admission . SETTING university-affiliated geriatric hospital and the homes of elderly patients . SUBJECTS 545 patients with acute illnesses admitted from home to the geriatric hospital . INTERVENTIONS patients were r and omly assigned to receive either comprehensive geriatric assessment and post-discharge home intervention ( intervention ) , comprehensive geriatric assessment alone ( assessment ) or usual care . MAIN OUTCOME MEASURES survival , functional status , rehospitalization , nursing home placement and direct costs over 12 months . RESULTS the intervention group showed a significant reduction in length of hospital stay ( 33.49 days vs 40.7 days in the assessment group and 42.7 days in the control group ; P < 0.05 ) and rate of immediate nursing home placement ( 4.4 % vs 7.3 % and 8.1 % ; P < 0.05 ) . There was no difference in survival , acute care hospital readmissions or new admissions to nursing homes but the intervention group had significantly shorter hospital readmissions ( 22.2 days vs 34.2 days and 35.7 days ; P < 0.05 ) and nursing home placements ( 114.7 days vs 161.6 days and 170.0 days ; P < 0.05 ) . Direct costs were lower in the intervention group [ about DM 7000 ( US $ 4000 ) per person per year ] . Functional capacities were significantly better in the intervention group . CONCLUSIONS comprehensive geriatric assessment in combination with post-discharge home intervention does not improve survival , but does improve functional status and can reduce the length of the initial hospital stay and of subsequent readmissions . It can reduce the rate of immediate nursing home admissions and delay permanent nursing home placement . It may also substantially reduce direct costs of hospitalized patients OBJECTIVE To determine the effect of a home-based intervention ( HBI ) on the frequency of unplanned readmission and out-of-hospital death among patients discharged home from acute hospital care . DESIGN A r and omized controlled trial comparing HBI with usual care ( UC ) . SETTING A tertiary referral hospital servicing the northwestern region of Adelaide , South Australia . PARTICIPANTS Medical and surgical patients ( n = 762 ) discharged home after hospitalization . INTERVENTION Home-based intervention ( n = 381 ) consisted of counseling of all patients before discharge followed by a single home visit ( by a nurse and pharmacist ) to those patients considered to be at high risk of readmission ( n = 314 ) in order to optimize compliance with and knowledge of the treatment regimen , identify early clinical deterioration , and intensify follow-up of such patients where appropriate . MEASUREMENTS The primary endpoint was the number of unplanned readmissions plus out-of-hospital deaths over a 6-month follow-up period . RESULTS During the study follow-up , the major endpoint occurred most commonly in the UC group ( 217 vs 155 episodes : P < .001 ) . Overall , the HBI group demonstrated fewer unplanned readmissions ( 154 vs 197 : P = .022 ) , out-of-hospital deaths ( 1 vs. 20 : P < .001 ) , total deaths ( 12 vs. 29 : P = .006 ) , emergency department attendances ( 236 vs 314 : P < .001 ) , and total days of hospitalization ( 1452 vs 1766 : P < .001 ) . There was a disproportionate reduction in multiple events among HBI patients ( P = .035 ) . Hospital-based costs of health care during study follow-up tended to be lower in the HBI group ( $ A2190 vs $ A2680 per patient : P = .102 ) . Mean cost of HBI was $ A190 per patient visited , whereas other community-based health care costs were similar for both groups . CONCLUSIONS Among high-risk patients discharged from acute hospital care , HBI is beneficial in limiting unplanned readmissions and reducing risk of out-of-hospital death . It may be particularly cost-effective if applied selectively to patients with a history of frequent unplanned hospital admission STUDY OBJECTIVE : We determine the cost-effectiveness of a 2-stage emergency department intervention in addition to usual ED care compared with that of usual care alone . METHODS The intervention comprises 2 steps : ( 1 ) identification of high-risk patients by using a screening tool and ( 2 ) a brief st and ardized nursing assessment to identify unresolved problems , followed by referral to an appropriate community provider . The patient population was composed of individuals aged 65 years and older to be released from the EDs of 4 Montreal hospitals . Patients were r and omized by day of ED visit . The perspective of the study is societal , including patients , caregivers , and the formal health care ( government-funded ) system . Outcomes , measured from r and omization to 4 months after r and omization , included ( 1 ) functional decline , as measured by an activities of daily living instrument , or death , and ( 2 ) changes in depressive symptoms . Costs include post-ED care , including hospitalization , physician services , community care , outpatient drugs , and patient and caregiver costs . Cost items were measured with administrative data bases and self-reported question naires . Unit costs for these items were either province-wide rates or else were estimated directly by using provider data . Cost-effectiveness is assessed in qualitative terms , such that outcomes and costs are compared separately . RESULTS The intervention was associated with a reduced rate of functional decline ( including death ) at 4 months . There was no effect of the intervention on change in the patient 's depressive symptoms at 4 months relative to baseline . The estimated ratio of overall costs per patient in the intervention versus the control group , adjusted for covariates , was 0.94 ( 95 % credible interval 0.75 to 1.17 ) . Among patients who had visited the ED during the 30 days before the index visit , the ratio was 0.66 ( 95 % credible interval 0.44 to 0.97 ) . CONCLUSION In this study setting , the intervention is preferred over usual care because beneficial functional outcomes were observed , and overall societal costs were no higher than if usual care only was given The complex chronic health problems and functional limitations common in the elderly population place them at risk for complicated hospitalizations and discharge planning . The purpose of this study was to investigate the effectiveness of a discharge planning protocol in identifying elderly patients ' home care needs . The sample in this quasiexperimental study consisted of 507 hospitalized patients age 65 years or older . The control group received the usual hospital discharge planning protocol . In the experimental group , nurse/social worker teams coordinated the discharge planning process , using an adapted form of the Discharge Planning Question naire ( DPQ ) to identify the home care needs of elderly patients . Thirty days after hospital discharge , both patient groups participated in a telephone survey to obtain information about health care problems they experienced during home recovery and their use of health care re sources . The findings indicated that the majority of the elderly patients had functional dependencies , which required the help of another person to carry out daily household duties and provide assistance with basic needs , especially ambulation . These functionally dependent patients only received home care referrals about 50 % of the time . These findings raise questions about current reimbursable services . Logistic regression analysis indicated that patients with increased functional dependency and patient problems during home recovery had a greater likelihood of rehospitalization and emergency department usage . This information about the home care of elderly patients after hospitalization supports the need for comprehensive functional assessment as part of discharge planning . This study also suggests that the nurse/social worker team can provide effective screening and discharge planning coordination of home care . Physician involvement and effective communication networks must be in place OBJECTIVE To determine the impact of a hospital-coordinated discharge care plan , involving a multidisciplinary team of primary health care providers , on hospital length of stay , quality of life , and both patient and general practitioner inclusion in , and satisfaction with , discharge procedures . DESIGN This investigation comprised a prospect i ve , r and omized , controlled , clinical trial . SETTING This multicentre and cross-jurisdictional study focused on areas of tertiary and primary health care as well as community allied health in Western Australia . PARTICIPANTS Patients ( n = 189 ) with chronic cardiorespiratory diagnoses were recruited from respiratory , cardiovascular , and general medical wards at two tertiary hospitals . INTERVENTION Subjects were r and omly assigned to one of two groups . Intervention group patients received a discharge care plan in accordance with that outlined in the Australian Enhanced Primary Care Package , completed before discharge and sent to the patient 's general practitioner and other community service providers for review . Control patients were discharged under existing hospital processes . Outcome measures . Patients and general practitioners were surveyed pre-discharge and 7 days post-discharge for quality of life and opinion of discharge procedures . Hospital length of stay was also determined . RESULTS Significant improvements in discharge planning involvement , health service access , confidence with discharge procedures , and opinion of discharge based on previous experience were seen for patients who received the discharge care plan . Further , improved perceptions of mental quality of life were observed within the first week post-discharge for intervention patients . Length of stay showed no difference between groups . Extent and speed of hospital-general practitioner communication were significantly improved via the intervention . CONCLUSIONS Our results indicate that a multidisciplinary discharge care plan , initiated before separation , improves quality of life , involvement , and satisfaction with discharge care , and hospital-general practitioner integration . As such , it possesses benefits over current Western Australian hospital discharge procedures for the care of chronically ill population Background . The growing number of patients with congestive heart failure has increased both the pressure on hospital re sources and the need for community management of the condition . Improving hospital-to-home transition for this population is a logical step in responding to current practice guidelines ’ recommendations for coordination and education . Positive outcomes have been reported from trials evaluating multiple interventions , enhanced hospital discharge , and follow-up through the addition of a case management role . The question remains if similar gains could be achieved working with usual hospital and community nurses . Methods . A 12-week , prospect i ve , r and omized controlled trial was conducted of the effect of transitional care on health-related quality of life ( disease-specific and generic measures ) , rates of readmission , and emergency room use . The nurse-led intervention focused on the transition from hospital-to-home and supportive care for self-management 2 weeks after hospital discharge . Results . At 6 weeks after hospital discharge , the overall Minnesota Living with Heart Failure Question naire ( MLHFQ ) score was better among the Transitional Care patients ( 27.2 ± 19.1 SD ) than among the Usual Care patients ( 37.5 ± 20.3 SD;P = 0.002 ) . Similar results were found at 12 weeks postdischarge for the overall MLHFQ and at 6- and 12-weeks postdischarge for the MLHFQ ’s Physical Dimension and Emotional Dimension subscales . Differences in generic quality life , as assessed by the SF-36 Physical component , Mental Component , and General Health subscales , were not significantly different between the Transition and Usual Care groups . At 12 weeks postdischarge , 31 % of the Usual Care patients had been readmitted compared with 23 % of the Transitional Care patients ( P = 0.26 ) , and 46 % of the Usual Care group visited the emergency department compared with 29 % in the Transitional Care group ( & khgr;2 = 4.86 , df 1 , P = 0.03 ) . Conclusions . There were significant improvements in health-related quality of life ( HRQL ) associated with Transitional Care and less use of emergency rooms The cost-effectiveness of a post-discharge programme on the use of hospital care and the continuity of care was assessed in an elderly cohort ( n = 204 ) discharged from the city hospital . The participation rate was 97.6 % , and the patients were aged 75 years or over and lived alone . The r and omized controls ( n = 204 ) received st and ard aftercare . During the follow-up the costs of university hospital care decreased by 52 % in the intervention group and by 24 % in the control group per patient year , compared with the costs in the year preceding the project . This happened despite the higher morbidity in the intervention group in terms of fractures and the use of university hospital care in the year preceding the project . There was also a tendency in the intervention group for the previous non-users of university hospital care to remain non-users during the follow-up . The costs of city hospital care increased by 16 % and 5 % , and of all hospital care by 1.3 % and 0.2 % , respectively . There were no differences in admissions to permanent care in the nursing homes . The intervention group did not make their first contact with the hospitals or permanent care in nursing homes earlier than the control group during the follow-up . The co-operation between hospital and domiciliary care and voluntary workers was well-suited to the innovative care of the elderly people Hospital discharge planning has become increasingly important in an era of prospect i ve payment and managed care . Given the changes in tasks , decisions , and environments involved , it is important to identify how to move such planning from an art to an empirically based decisionmaking process . The authors use a decision-sciences framework to review the state-of-the-art of hospital discharge planning and to suggest methods for improvement OBJECTIVES To evaluate an interdisciplinary intervention program for older people with hip fracture in Taiwan . DESIGN R and omized experimental design . SETTING A 3,800-bed medical center in northern Taiwan . PARTICIPANTS Elderly patients with hip fracture ( N=137 ) were r and omly assigned to an experimental ( n=68 ) or control ( n=69 ) group . INTERVENTION An interdisciplinary program of geriatric consultation , continuous rehabilitation , and discharge planning . MEASUREMENTS Demographic and outcome variables were measured . Outcome variables included service utilization , clinical outcomes , self-care abilities , health-related quality -of-life ( HRQOL ) outcomes , and depressive symptoms . RESULTS Subjects in the experimental group improved significantly more than those in the control group in the following outcomes : ratio of hip flexion 1 month after discharge ( P=.02 ) , recovery of previous walking ability at 1 month ( P=.04 ) and 3 months ( P=.001 ) after discharge , and activities of daily living at 1 month ( P=.01 ) and 2 months ( P=.001 ) after discharge . Three months after discharge , the experimental group showed significant improvement in peak force of the fractured limb 's quadriceps ( P=.04 ) and the following health outcomes : bodily pain ( P=.03 ) , vitality ( P<.001 ) , mental health ( P=.02 ) , physical function ( P<.001 ) , and role physical ( P=.006 ) . They also had fewer depressive symptoms ( P=.008 ) 3 months after discharge . CONCLUSION This intervention program may benefit older people with hip fractures in Taiwan by improving their clinical outcomes , self-care abilities , and HRQOL and by decreasing depressive symptoms within 3 months after discharge OBJECTIVE We aim ed to assess whether GP input into discharge planning for high-risk aged in- patients admitted under the care of a geriatrician results in improved patient outcomes . METHODS We conducted a prospect i ve r and omized controlled trial in Sydney , Australia . The subjects were 364 patients aged 60 years and over . The main outcome measures included community service referral , accommodation changes , length of stay , readmission rate , length of time to first readmission and patient satisfaction with discharge arrangements . RESULTS No significant differences were found with regard to length of stay , readmission rates or time to first readmission . Test-group subjects were significantly more likely to be recommended for community services at discharge and to report that hospital personnel had discussed their discharge plan with them . Significantly more of the test group reported that their return home was well prepared . CONCLUSIONS Although GP pre-discharge visits did not alter the likelihood of ' hard outcomes such as risk of readmission ' , the results suggest that quality of care is enhanced amongst patients receiving a pre-discharge visit and that GPs can perform a key role in planning post-discharge care with other services Abstract Objective : To compare effectiveness and acceptability of early discharge to a hospital at home scheme with that of routine discharge from acute hospital . Design : Pragmatic r and omised controlled trial . Setting : Acute hospital wards and community in north of Bristol , with a catchment population of about 224 000 people . Subjects : 241 hospitalised but medically stable elderly patients who fulfilled criteria for early discharge to hospital at home scheme and who consented to participate . Interventions : Patients ' received hospital at home care or routine hospital care . Main outcome measures : Patients ' quality of life , satisfaction , and physical functioning assessed at 4 weeks and 3 months after r and omisation to treatment ; length of stay in hospital and in hospital at home scheme after r and omisation ; mortality at 3 months . Results : There were no significant differences in patient mortality , quality of life , and physical functioning between the two arms of the trial at 4 weeks or 3 months . Only one of 11 measures of patient satisfaction was significantly different : hospital at home patients perceived higher levels of involvement in decisions . Length of stay for those receiving routine hospital care was 62 % ( 95 % confidence interval 51 % to 75 % ) of length of stay in hospital at home scheme . Conclusions : The early discharge hospital at home scheme was similar to routine hospital discharge in terms of effectiveness and acceptability . Increased length of stay associated with the scheme must be interpreted with caution because of different organisational characteristics of the services . Key messages Pressure on hospital beds , the increasing age of the population , and high costs associated with acute hospital care have fuelled the search for alternatives to inpatient hospital care There were no significant differences between early discharge to hospital at home scheme and routine hospital care in terms of patient quality of life , physical functioning , and most measures of patient satisfaction Length of stay for hospital patients was significantly shorter than that of hospital at home patients , but , owing to qualitative differences between the two interventions , this does not necessarily mean differences in effectiveness Early discharge to hospital at home provides an acceptable alternative to routine hospital care in terms of effectiveness and patient OBJECTIVE To determine whether there was any benefit from a single house call by a health visitor ( a public health nurse ) to an elderly person after discharge home from a geriatric hospital . METHODS A r and omized controlled trial with blind assessment s at 28 days was conducted . Subjects included residents of Bath , Engl and , with an average age of 83 years , who were discharged consecutively from a geriatric hospital to their homes . Intervention was a single visit by a health visitor 72 hours after discharge , to ensure the patient was settled at home , or normal post-discharge care . Outcome measures taken at 28 days by a research nurse included survival , hospital readmissions , nursing home admissions , cognitive and physical function , services requested and supplied , and drug therapy . RESULTS There were no important differences between the intervention and control groups at 28 days on any of the outcome measurements . The control subjects did better than the study subjects on many of the outcome measures . CONCLUSION A house call by a health visitor to elderly patients after discharge from geriatric wards does not measurably improve the quality of the discharge BACKGROUND Multiple hospital admissions , especially those related to chronic disease , represent a particular challenge to the acute health care sector in Australia . OBJECTIVE To determine whether a nurse-led chronic disease management model of transitional care reduced readmissions to acute care . DESIGN A quasi-experimental controlled trial . SETTING A large tertiary metropolitan teaching hospital . PARTICIPANTS 166 general medical patients aged > or = 65 years with either a history of readmissions to acute care or multiple medical comorbidities . INTERVENTION Implementation of a chronic disease management model of transitional care aim ed at improving patient management and reducing readmissions to acute care . MAIN OUTCOME MEASURES Readmission rates and emergency department presentation rates at 3- and 6-month follow up . Secondary outcome measures include quality of life , discharge destination , and primary health care service utilisation . RESULTS There was no difference in readmission rates , emergency department presentation rates , quality of life , discharge destination or primary health care service utilisation . The difficulties inherent in evaluating this type of multifactorial intervention are discussed and consideration is given to patient factors , the difficulty of influencing readmission rates , and local system issues . CONCLUSION The outcomes of this study reflect the tension that exists between implementing multifaceted integrated health service programs and attempting to evaluate them within complex and changing environments using robust research method ologies BACKGROUND Older persons frequently experience a decline in function following an acute medical illness and hospitalization . OBJECTIVE To test the hypothesis that a multicomponent intervention , called Acute Care for Elders ( ACE ) , will improve functional outcomes and the process of care in hospitalized older patients . DESIGN R and omized controlled trial . SETTING Community teaching hospital . PATIENTS A total of 1,531 community-dwelling patients , aged 70 or older , admitted for an acute medical illness between November 1994 and May 1997 . INTERVENTION ACE includes a specially design ed environment ( with , for example , carpeting and uncluttered hallways ) ; patient-centered care , including nursing care plans for prevention of disability and rehabilitation ; planning for patient discharge to home ; and review of medical care to prevent iatrogenic illness . MEASUREMENTS The main outcome was change in the number of independent activities of daily living ( ADL ) from 2 weeks before admission ( baseline ) to discharge . Secondary outcomes included re source use , implementation of orders to promote function , and patient and provider satisfaction . RESULTS Self-reported measures of function did not differ at discharge between the intervention and usual care groups by intention-to-treat analysis . The composite outcome of ADL decline from baseline or nursing home placement was less frequent in the intervention group at discharge ( 34 % vs 40 % ; P = .027 ) and during the year following hospitalization ( P = .022 ) . There were no significant group differences in hospital length of stay and costs , home healthcare visits , or readmissions . Nursing care plans to promote independent function were more often implemented in the intervention group ( 79 % vs 50 % ; P = .001 ) , physical therapy consults were obtained more frequently ( 42 % vs 36 % ; P = .027 ) , and restraints were applied to fewer patients ( 2 % vs 6 % ; P = .001 ) . Satisfaction with care was higher for the intervention group than the usual care group among patients , caregivers , physicians , and nurses ( P < .05 ) . CONCLUSIONS ACE in a community hospital improved the process of care and patient and provider satisfaction without increasing hospital length of stay or costs . A lower frequency of the composite outcome ADL decline or nursing home placement may indicate potentially beneficial effects on patient outcomes Discharge planning impacts hospital costs and patient outcomes . The purpose of this study was to determine the effects of a structured discharge planning program using collaboration between the CNS and the social worker . The quasi-experimental study used a sample of 64 elderly patients . The experimental group ( n = 29 ) had discharge planning directed through collaboration by a CNS and a social worker . After discharge , patients were contacted by telephone about satisfaction and services received . Charts were review ed for information about length of stay , readmission , and documentation . Data analysis revealed that patients involved in collaborative planning were more satisfied , had a shorter length of stay , had fewer readmissions , and received a higher rate of indicated postdischarge services . Documentation was not significantly affected , except in the area of patient teaching , which was lower in the experimental group . Based on these findings , the collaborative model offers nurse administrators a way to improve outcomes for patients and the organization OBJECTIVE To survey adult medical and surgical patients about their concerns and satisfaction with their care in Canadian hospitals . DESIGN Cross-sectional telephone survey undertaken from June 1991 to May 1992 with a st and ardized question naire . SETTING Stratified r and om sample of public acute care hospitals in six provinces ; 57 ( 79 % ) of the 72 hospitals approached agreed to participate . PATIENTS Each participating hospital provided the study team with the names of 150 adult medical and surgical patients discharged home in consecutive order . A total of 4599 patients agreed to be interviewed ( 69 % of eligible patients and 89 % of patients contacted ) . MAIN OUTCOME MEASURES Satisfaction with ( a ) provider-patient communication ( including information given ) , ( b ) provider 's respect for patient 's preferences , ( c ) attentiveness to patient 's physical care needs , ( d ) education of patient regarding medication and tests , ( e ) quality of relationship between patient and physician in charge , ( f ) education of and communication with patient 's family regarding care , ( g ) pain management and ( h ) hospital discharge planning . RESULTS Most ( 61 % ) of the patients surveyed reported problems with 5 or fewer of the 39 specific care processes asked about in the study . Forty-one percent of the patients reported that they had not been told about the daily hospital routines . About 20 % of the patients receiving medications reported that they had not been told about important side effects in a way they could underst and ; 20 % of the patients who underwent tests reported similar problems with communication of the test results . Thirty-six percent of those having tests had not been told how much pain to expect . In discharge planning , the patients complained that they had not been told what danger signals to watch for at home ( reported by 39 % ) , when they could resume normal activities ( by 32 % ) and what activities they could or could not do at home ( by 29 % ) . Over 90 % of the patients reported that they had had a relationship of confidence and trust with their physician and that they had been involved in decision making as much as they wanted to be . Fifteen percent of the patients whose admissions had been scheduled felt that they should have been admitted sooner . CONCLUSION The self-reported patient data from this survey suggest that hospital routines , medications , tests , pain management and discharge planning are areas of communication to target in future quality -improvement efforts in Canadian hospitals OBJECTIVES To examine the effectiveness of a transitional care intervention delivered by advanced practice nurses ( APNs ) to elders hospitalized with heart failure . DESIGN R and omized , controlled trial with follow-up through 52 weeks postindex hospital discharge . SETTING Six Philadelphia academic and community hospitals . PARTICIPANTS Two hundred thirty-nine eligible patients were aged 65 and older and hospitalized with heart failure . INTERVENTION A 3-month APN-directed discharge planning and home follow-up protocol . MEASUREMENTS Time to first rehospitalization or death , number of rehospitalizations , quality of life , functional status , costs , and satisfaction with care . RESULTS Mean age of patients ( control n=121 ; intervention n=118 ) enrolled was 76 ; 43 % were male , and 36 % were African American . Time to first readmission or death was longer in intervention patients ( log rank chi(2)=5.0 , P=.026 ; Cox regression incidence density ratio=1.65 , 95 % confidence interval=1.13 - 2.40 ) . At 52 weeks , intervention group patients had fewer readmissions ( 104 vs 162 , P=.047 ) and lower mean total costs ( $ 7,636 vs $ 12,481 , P=.002 ) . For intervention patients , only short-term improvements were demonstrated in overall quality of life ( 12 weeks , P<.05 ) , physical dimension of quality of life ( 2 weeks , P<.01 ; 12 weeks , P<.05 ) and patient satisfaction ( assessed at 2 and 6 weeks , P<.001 ) . CONCLUSION A comprehensive transitional care intervention for elders hospitalized with heart failure increased the length of time between hospital discharge and readmission or death , reduced total number of rehospitalizations , and decreased healthcare costs , thus demonstrating great promise for improving clinical and economic outcomes BACKGROUND Congestive heart failure is the most common indication for admission to the hospital among older adults . Behavioral factors , such as poor compliance with treatment , frequently contribute to exacerbations of heart failure , a fact suggesting that many admissions could be prevented . METHODS We conducted a prospect i ve , r and omized trial of the effect of a nurse-directed , multidisciplinary intervention on rates of readmission within 90 days of hospital discharge , quality of life , and costs of care for high-risk patients 70 years of age or older who were hospitalized with congestive heart failure . The intervention consisted of comprehensive education of the patient and family , a prescribed diet , social-service consultation and planning for an early discharge , a review of medications , and intensive follow-up . RESULTS Survival for 90 days without readmission , the primary outcome measure , was achieved in 91 of the 142 patients in the treatment group , as compared with 75 of the 140 patients in the control group , who received conventional care ( P = 0.09 ) . There were 94 readmissions in the control group and 53 in the treatment group ( risk ratio , 0.56 ; P = 0.02 ) . The number of readmissions for heart failure was reduced by 56.2 percent in the treatment group ( 54 vs. 24 , P = 0.04 ) , whereas the number of readmissions for other causes was reduced by 28.5 percent ( 40 vs. 29 , P not significant ) . In the control group , 23 patients ( 16.4 percent ) had more than one readmission , as compared with 9 patients ( 6.3 percent ) in the treatment group ( risk ratio , 0.39 ; P = 0.01 ) . In a subgroup of 126 patients , quality -of-life scores at 90 days improved more from base line for patients in the treatment group ( P = 0.001 ) . Because of the reduction in hospital admissions , the overall cost of care was $ 460 less per patient in the treatment group . CONCLUSIONS A nurse-directed , multidisciplinary intervention can improve quality of life and reduce hospital use and medical costs for elderly patients with congestive heart failure OBJECTIVES To study the effects of comprehensive geriatric assessment ( CGA ) and multidisciplinary intervention on elderly patients sent home from the emergency department ( ED ) . DESIGN Prospect i ve , r and omized , controlled trial with 18 months of follow-up . SETTING Large medical school-affiliated public hospital in an urban setting in Sydney , Australia . PARTICIPANTS A total of 739 patients aged 75 and older discharged home from the ED were r and omized into two groups . INTERVENTION Patients r and omized to the treatment group underwent initial CGA and were followed at home for up to 28 days by a hospital-based multidisciplinary outreach team . The team implemented or coordinated recommendations . The control group received usual care . MEASUREMENTS The primary outcome measure was all admissions , to the hospital within 30 days of the initial ED visit . Secondary outcome measures were elective and emergency admissions , and nursing home admissions and mortality . Additional outcomes included physical function ( Barthel Index ( total possible score=20 ) and instrumental activities of daily living ( /12 ) and cognitive function ( mental status question naire ( /10 ) ) . RESULTS Intervention patients had a lower rate of all admissions to the hospital during the first 30 days after the initial ED visit ( 16.5 % vs 22.2 % ; P=.048 ) , a lower rate of emergency admissions during the 18-month follow-up ( 44.4 % vs 54.3 % ; P=.007 ) , and longer time to first emergency admission ( 382 vs 348 days ; P=.011 ) . There was no difference in admission to nursing homes or mortality . Patients r and omized to the intervention group maintained a greater degree of physical and mental function ( Barthel Index change from baseline at 6 months : -0.25 vs -0.75 ; P<.001 ; mental status question naire change from baseline at 12 months : -0.21 vs -0.64 ; P<.001 ) . CONCLUSION CGA and multidisciplinary intervention can improve health outcomes of older people at risk of deteriorating health and admission to hospital . Patients aged 75 and older should be referred for CGA after an ED visit Background and aims : In a previous publication , we showed that treatment of acutely sick , frail elderly patients in a Geriatric Evaluation and Management Unit ( GEMU ) reduced mortality considerably when compared with the general Medical Wards ( MW ) . The aim of this presentation was to study the impact of treatment in a GEMU on health care utilization . Methods : Acutely sick , frail patients , 75 years or older , who had been admitted as emergencies to the Department of Internal Medicine were r and omized either to treatment in the GEMU ( n=127 ) or to continued treatment in the MW ( n=127 ) . While usual treatment was given in the MW , the GEMU emphasized interdisciplinary and comprehensive assessment of all relevant disorders , early mobilization/rehabilitation , and discharge planning . After discharge from hospital , no specific follow-up was offered to any of the groups . Results : Of all subjects , 101 ( 80 % ) GEMU and 79 ( 64 % ) MW patients were still living in their own homes at three months ( p=0.005 ) ; at six months the number was 91 ( 72 % ) and 74 ( 60 % ) ( p=0.04 ) respectively . Median length of index stay was 19 days in the GEMU and 13 days in the MW group ( p<0.001 ) . After the initial stay , there were no statistically significant differences in admissions to or time spent in institutions . Conclusions : The results indicate the overall positive treatment effect of acutely sick , frail elderly in a GEMU , i.e. patients treated in the GEMU had increased possibilities of living in their own homes , an effect that was mainly related to considerably reduced mortality in the GEMU group Objective The aim of this study was to examine the effect of psychogeriatric intervention in a group of elderly medical in patients over 75 years of age . In addition to usual care , intervention consisted of multidisciplinary joint treatment by a psychogeriatric team . The main purpose of intervention was to obtain the optimal level of physical functioning . Method In a prospect i ve r and omized trial the effect of the intervention ( N = 140 ) compared with usual care ( N = 97 ) was estimated for physical functioning , length of stay , and nursing home placement within 12 months of discharge . Results Substantially more patients assigned to the intervention group improved in their physical functioning , and fewer became worse . The mean length of stay was 5 days shorter for the intervention group . There were more readmissions to hospital in the usual care group ( 29.9 % ) compared with the intervention group ( 17.4 % ) . Of the patients assigned to the intervention treatment , 18 % were admitted to a nursing home . In the usual care group this was 27 % . The effects of intervention remained statistically significant for all the outcome variables after controlling for possible confounding baseline characteristics . Conclusions The intervention we studied had clinical ly relevant effects on important outcome variables . Psychiatric co-morbidity was an important risk factor for the outcome of the patients in our study . By combining elements from a psychiatric and geriatric consultation service with elements from a unit-driven service , we were able to improve health care for the elderly in our hospital in a feasible and cost-effective way A preadmission social work intervention was evaluated for impact on length of hospital stay ( LOS ) and patient satisfaction . Psychosocial issues related to function and post-discharge needs were assessed at an exploratory level . A modified post-test only control group design was used . Study group patients were screened before hospitalization and offered services on admission . Control group patients received st and ard care . Study group patients were significantly more satisfied with services but impact on length of stay was not demonstrated with one possible exception . Post-operative complications were significantly related to longer LOS ; however , unlike control group patients , study group patients with complications did not have significantly longer LOS . Women and those limited in preadmission physical function were most likely to report insufficient help after discharge . A more intensive preadmission intervention is recommended to improve impact on LOS and informal support system involvement , while future outcome studies would clarify the nature of service gaps and high risk groups OBJECTIVES To evaluate the effectiveness of an intensive community nurse (CN)-supported discharge program in preventing hospital readmissions of older patients with chronic lung disease ( CLD ) . DESIGN R and omized , controlled trial . SETTING Two acute hospitals in the same health region in Hong Kong . PARTICIPANTS One hundred fifty-seven hospitalized patients aged 60 and older with a primary diagnosis of CLD and at least one hospital admission in the previous 6 months . INTERVENTION CNs made home visits within 7 days of discharge , then weekly for 4 weeks and monthly until 6 months . CNs coordinated closely with a geriatric or respiratory specialist in hospital . Subjects had telephone access to CNs during normal working hours from Monday to Saturday . MEASUREMENTS The primary outcome was the rate of unplanned readmission within 6 months . The secondary outcomes were the rate of unplanned readmission within 28 days , number of unplanned readmissions , hospital bed days , accident and emergency room attendance , functional and psychosocial status , and caregiver burden . RESULTS One hundred forty hospitalized patients completed the trial . Intervention group subjects had a higher rate of unplanned readmission within 6 months than control group subjects ( 76 % vs 62 % , P=.080 , chi2 test ) . There was no significant group difference in any of the secondary outcomes except that intervention group subjects did better on social h and icap scores . CONCLUSION There was no evidence that an intensive CN-supported discharge program can prevent hospital readmissions in older patients with CLD OBJECTIVE To evaluate the benefits of coordinating community services through the Post-Acute Care ( PAC ) program in older patients after discharge from hospital . DESIGN Prospect i ve multicentre , r and omised controlled trial with six months of follow-up with blinded outcome measurement . SETTING Four university-affiliated metropolitan general hospitals in Victoria . PARTICIPANTS All patients aged 65 years and over who were discharged between August 1998 and October 1999 and required community services after discharge . INTERVENTIONS Participants were r and omly allocated to receive services of a Post-Acute Care ( PAC ) coordinator ( intervention ) versus usual discharge planning ( control ) . MAIN OUTCOME MEASURES Comparison of quality of life and carer stress at one-month post-discharge , mortality , hospital readmissions , use of community services and community and hospital costs over the six months post-discharge . RESULTS 654 patients were r and omised , and 598 were included in the analysis ( 311 in the PAC group and 287 in the control group ) . There was no difference in mortality between the groups ( both 6 % ) , but significantly greater overall quality -of-life scores at one-month follow-up in the PAC group . There was no difference in unplanned readmissions , but PAC patients used significantly fewer hospital bed-days in the six months after discharge ( mean , 3.0 days ; 95 % CI , 2.1 - 3.9 ) than control patients ( 5.2 days ; 95 % CI , 3.8 - 6.7 ) . Total costs ( including hospitalisation , community services and the intervention ) were lower in the PAC than the control group ( mean difference , $ 1545 ; 95 % CI , $ 11-$3078 ) . CONCLUSIONS The PAC program is beneficial in the transition from hospital to the community in older patients |
2,225 | 28,181,487 | Photobiomodulation in animal models showed consistently positive effects over a range of wavelengths and application parameters , with reductions in total infa rct size ( up to 76 % ) , decreases in inflammation and scarring , and increases in tissue repair .
Multiple molecular pathways were identified , including modulation of inflammatory cytokines , signalling molecules , transcription factors , enzymes and antioxidants . | Myocardial ischemia reperfusion injury is a negative pathophysiological event that may result in cardiac cell apoptosis and is a result of coronary revascularization and cardiac intervention procedures .
The result ing loss of cardiomyocyte cells and the formation of scar tissue , leads to impaired heart function , a major prognostic determinant of long-term cardiac outcomes .
Photobiomodulation is a novel cardiac intervention that has displayed therapeutic effects in reducing myocardial ischemia reperfusion related myocardial injury in animal models .
A growing body of evidence supporting the use of photobiomodulation in myocardial infa rct models has implicated multiple molecular interactions .
A systematic review was conducted to identify the strength of the evidence for the therapeutic effect of photobiomodulation and to summarise the current evidence as to its mechanisms . | The use of low levels of visible or near infrared light for reducing pain , inflammation and edema , promoting healing of wounds , deeper tissues and nerves , and preventing cell death and tissue damage has been known for over forty years since the invention of lasers . Despite many reports of positive findings from experiments conducted in vitro , in animal models and in r and omized controlled clinical trials , LLLT remains controversial in mainstream medicine . The biochemical mechanisms underlying the positive effects are incompletely understood , and the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength , fluence , power density , pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones . A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light . The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response . This review will cover the molecular and cellular mechanisms in LLLT , and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response BACKGROUND Experimental evidence suggests that cyclosporine , which inhibits the opening of mitochondrial permeability-transition pores , attenuates lethal myocardial injury that occurs at the time of reperfusion . In this pilot trial , we sought to determine whether the administration of cyclosporine at the time of percutaneous coronary intervention ( PCI ) would limit the size of the infa rct during acute myocardial infa rct ion . METHODS We r and omly assigned 58 patients who presented with acute ST-elevation myocardial infa rct ion to receive either an intravenous bolus of 2.5 mg of cyclosporine per kilogram of body weight ( cyclosporine group ) or normal saline ( control group ) immediately before undergoing PCI . Infa rct size was assessed in all patients by measuring the release of creatine kinase and troponin I and in a subgroup of 27 patients by performing magnetic resonance imaging ( MRI ) on day 5 after infa rct ion . RESULTS The cyclosporine and control groups were similar with respect to ischemia time , the size of the area at risk , and the ejection fraction before PCI . The release of creatine kinase was significantly reduced in the cyclosporine group as compared with the control group ( P=0.04 ) . The release of troponin I was not significantly reduced ( P=0.15 ) . On day 5 , the absolute mass of the area of hyperenhancement ( i.e. , infa rct ed tissue ) on MRI was significantly reduced in the cyclosporine group as compared with the control group , with a median of 37 g ( interquartile range , 21 to 51 ) versus 46 g ( interquartile range , 20 to 65 ; P=0.04 ) . No adverse effects of cyclosporine administration were detected . CONCLUSIONS In our small , pilot trial , administration of cyclosporine at the time of reperfusion was associated with a smaller infa rct by some measures than that seen with placebo . These data are preliminary and require confirmation in a larger clinical trial Background Remote ischemic preconditioning ( RIPC ) has been shown to enhance the tolerance of remote organs to cope with a subsequent ischemic event . We hypothesized that RIPC reduces postoperative neurocognitive dysfunction ( POCD ) in patients undergoing complex cardiac surgery . Methods We conducted a prospect i ve , r and omized , double-blind , controlled trial including 180 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass . Patients were r and omized either to RIPC or to control group . Primary endpoint was postoperative neurocognitive dysfunction 5–7 days after surgery assessed by a comprehensive test battery . Cognitive change was assumed if the preoperative to postoperative difference in 2 or more tasks assessing different cognitive domains exceeded more than one SD ( 1 SD criterion ) or if the combined Z score was 1.96 or greater ( Z score criterion ) . Results According to 1 SD criterion , 52 % of control and 46 % of RIPC patients had cognitive deterioration 5–7 days after surgery ( p = 0.753 ) . The summarized Z score showed a trend to more cognitive decline in the control group ( 2.16±5.30 ) compared to the RIPC group ( 1.14±4.02 ; p = 0.228 ) . Three months after surgery , incidence and severity of neurocognitive dysfunction did not differ between control and RIPC . RIPC tended to decrease postoperative troponin T release at both 12 hours [ 0.60 ( 0.19–1.94 ) µg/L vs. 0.48 ( 0.07–1.84 ) µg/L ] and 24 hours after surgery [ 0.36 ( 0.14–1.89 ) µg/L vs. 0.26 ( 0.07–0.90 ) µg/L ] . Conclusions We failed to demonstrate efficacy of a RIPC protocol with respect to incidence and severity of POCD and secondary outcome variables in patients undergoing a wide range of cardiac surgery . Therefore , definitive large-scale multicenter trials are needed . Trial Registration Clinical Trials.gov OBJECTIVE The aim of this r and omized , placebo-controlled , double-blind trial was to investigate changes in the content of 10 cytokines in the human peripheral blood after transcutaneous and in vitro irradiation with polychromatic visible and infrared ( IR ) polarized light at therapeutic dose . BACKGROUND DATA The role of cytokines in development of anti-inflammatory , immunomodulatory , and wound-healing effects of visible and IR light remains poorly studied . METHODS The sacral area of volunteers was exposed ( 480 - 3400 nm , 95 % polarization , 12 J/cm(2 ) ) ; in parallel , the blood sample s of the same subjects were irradiated in vitro ( 2.4 J/cm(2 ) ) . Determination of cytokine content was performed using enzyme-linked immunosorbent assay ( ELISA ) . RESULTS A dramatic decrease in the level of pro-inflammatory cytokines TNF-alpha , IL-6 , and IFN-gamma was revealed : at 0.5 h after exposure of volunteers ( with the initial parameters exceeding the norm ) , the cytokine contents fell , on average , 34 , 12 , and 1.5 times . The reduced concentrations of TNF-alpha and IL-6 were preserved after four daily exposures , whereas levels of IFN-gamma and IL-12 decreased five and 15 times . At 0.5 h and at later times , the amount of anti-inflammatory cytokines was found to rise : that of IL-10 rose 2.7 - 3.5 times ( in subjects with normal initial parameters ) and of TGF-beta1 1.4 - 1.5 times ( in the cases of its decreased level ) . A peculiarity of the light effect was a fast rise of IFN-gamma at 3.3 - 4.0 times in subjects with normal initial values . The content of IL-1beta , IL-2 , IFN-alpha , and IL-4 did not change . Similar regularities of the light effects were recorded after in vitro irradiation of blood , as well as on mixing the irradiated and non-irradiated autologous blood at a volume ratio 1:10 ( i.e. , at modeling the events in a vascular bed of the exposed person when a small amount of the transcutaneously photomodified blood contacts its main circulating volume ) . CONCLUSION Exposure of a small area of the human body to light leads to a fast decrease in the elevated pro-inflammatory cytokine plasma content and to an increase in the the anti-inflammatory factor concentration , which may be an important mechanism of the anti-inflammatory effect of phototherapy . These changes result from transcutaneous photomodification of a small volume of blood and a fast transfer of the light-induced changes to the entire pool of circulating blood Abstract We suggested that low-level laser irradiation ( LLLI ) precondition prior to cell transplantation might remodel the hostile milieu of infa rct ed myocardium and subsequently enhance early survival and therapeutic potential of implanted bone marrow mesenchymal stem cells ( BMSCs ) . Therefore , in this study we wanted to address : ( 1 ) whether LLLI pre-treatment change the local cardiac micro-environment after myocardial infa rct ion ( MI ) and ( 2 ) whether the LLLI preconditions enhance early cell survival and thus improve therapeutic angiogenesis and heart function . MI was induced by left anterior descending artery ligation in female rats . A 635 nm , 5 mW diode laser was performed with energy density of 0.96 J/cm2 for 150 sec. for the purpose of myocardial precondition . Three weeks later , qualified rats were r and omly received with LLLI precondition ( n= 26 ) or without LLLI precondition ( n= 27 ) for LLLI precondition study . Rats that received thoracotomy without coronary ligation were served as sham group ( n= 24 ) . In the cell survival study , rats were r and omly divided into 4 groups : serum-free culture media injection ( n= 8) , LLLI precondition and culture media injection ( n= 8) , 2 million male BMSCs transplantation without LLLI pre-treatment ( n= 26 ) and 2 million male BMSCs transplantation with LLLI precondition ( n= 25 ) group , respectively . Vascular endothelial growth factor ( VEGF ) , glucose-regulated protein 78 ( GRP78 ) , superoxide dismutase ( SOD ) and malondialdehyde ( MDA ) in the infa rct ed myocardium were evaluated by Western blotting , real-time PCR and colorimetry , respectively , at 1 hr , 1 day and 1 week after laser irradiation . Cell survival was assayed with quantitative real-time PCR to identify Y chromosome gene and apoptosis was assayed with transferase-mediated dUTP end labelling staining . Capillary density , myogenic differentiation and left ventricular function were tested by immunohistochemistry and echocardiography , respectively , at 1 week . After LLLI precondition , increased VEGF and GRP78 expression , as well as the enhanced SOD activity and inhibited MDA production , was observed . Compared with BMSC transplantation and culture media injection group , although there was no difference in the improved heart function and myogenic differentiation , LLLI precondition significantly enhanced early cell survival rate by 2-fold , decreased the apoptotic percentage of implanted BMSCs in infa rct ed myocardium and thus increased the number of newly formed capillaries . Taken together , LLLI precondition could be a novel non-invasive approach for intraoperative cell transplantation to enhance cell early survival and therapeutic potential The angioplasty procedure is associated with a release of numerous factors triggering the local inflammatory reaction in vascular wall and leading thus to the restenosis . In this study , we hypothesize that the low-energy laser irradiation may exert beneficial effect by limiting this process . A group of 101 subjects ( 75 men and 26 women , mean age : 59.1 ± 10.3 ) treated with percutaneous coronary intervention ( PCI ) , were recruited to this study . While 52 patients ( 40 men and 12 women ) were subjected to the intravascular low-energy laser irradiation ( λ = 808 nm ) of dilated lesion during the PCI , the remaining patients ( 35 men and 14 women ) constituted the control group . The levels of interleukin 1β , 6 and 10 ( IL 1β , IL 6 and IL 10 ) were measured immediately before the procedure , and then at the 6th , 12th hour as well as after 1 month following the PCI . Significantly lower levels of IL 1β and IL 6 in the irradiated group during each analysis after the procedure were observed . Moreover , significantly lower IL 10 level in irradiated group within 6 and 12 hours after PCI was observed . Irradiation of the lesion with low-energy laser radiation during the PCI procedure results in a decrease in the levels of pro-inflammatory IL 1β and IL 6 as well as in an increase in the levels of anti-inflammatory IL 10 , which may result in decreased risk for restenosis Objectives The usefulness and safety of percutaneous myocardial laser therapy in selected patients have been identified in previous 1-year r and omized trial reports , including that from a double-blind , sham-controlled trial we independently conducted . We aim ed to determine whether the 1-year effects are maintained through a long-term , longitudinal follow-up . Methods Patients ( n=77 ) with chronic , stable , medically refractory angina ( class III or IV ) not amenable to conventional revascularization and with evidence of reversible ischemia , ejection fraction ≥25 % , and myocardial wall thickness ≥8 mm were treated with percutaneous myocardial laser . After the 1-year follow-up and disclosure of all r and omized assignments as prespecified in the respective study protocol , patients were followed up longitudinally for a mean of 3 years for angina class , left ventricular ejection fraction , medication usage , and adverse events . Results No procedural mortality , myocardial infa rct ion , or cerebral embolism occurred . Pericardiocentesis was required in two patients ( 2.6 % ) . Cardiac event-free survival was 88 % at 1 year and 66 % at late follow-up . Mean Canadian Cardiovascular Society angina class was significantly improved from baseline ( 3.2±0.4 ) at 1 year ( 2.2±1.1 , P<0.001 ) and at a mean of 3 years ( 1.9±1.2 , P<0.001 ) . Nitrate usage was significantly reduced at late follow-up ; however , ejection fraction did not change over time . In a multivariate analysis , angina improvement at 1 year was found to be a significant independent predictor of both survival and angina improvement at late follow-up . Conclusion We conclude that percutaneous myocardial laser therapy in selected patients with severe , medically refractory angina not treatable with conventional revascularization induces significant and sustained symptomatic benefit BACKGROUND AND OBJECTIVE This study aim ed at analyzing the healing effects of low-level laser therapy ( LLLT ) ( λ620 nm , 6 J/cm2 ) and light-emitting diode ( LED ) therapy ( λ640 nm , 6 J/cm2 ) on the longitudinal sternotomy incisions of hyperglycemic and normoglycemic patients who underwent coronary artery bypass grafting ( CABG ) . MATERIAL S AND METHODS 120 volunteers were electively su bmi tted to CABG and were r and omly allocated into four different groups of equal size ( n = 30 ) : control , placebo , laser ( λ of 640 nm and spatial average energy fluency [ SAEF ] of 1.06 J/cm2 ) , and LED ( λ of 660 ± 20 nm and SAEF of 0.24 J/cm2 ) . Laser and LED groups were irradiated from the second to eighth day postsurgery , and sternotomy incision was photographically registered . Then , participants were also separated into hyperglycemic and normoglycemic groups , according to their fasting blood glucose test before surgery . Three research ers blindly analyzed the incision photographs to determine hyperemia and wound closure at the first day of hospital discharge ( eighth postoperative day ) . RESULTS LLLT and LED groups had similarly less hyperemia and less incision bleeding or dehiscence ( p ≤ 0.005 ) and the outcomes were also analogous between hyperglycemic and normoglycemic patients , which indicates no difference observed in an intragroup analysis ( p ≥ 0.05 ) . CONCLUSIONS With the present therapy parameters , it may be assumed that both coherent light ( laser ) and non-coherent light ( LED ) are effective in promoting sternotomy and healing acceleration , which are evident on the eighth day postsurgery This study aim ed to analyze the effects of light-emitting diode ( LED ) therapy on sternotomy pain and healing in patients who underwent coronary artery bypass grafting ( CABG ) . The patients were followed for 6 months after the surgery to determine their dehiscence . This study was conducted with 90 volunteers who electively su bmi tted to CABG . The volunteers were r and omly allocated into three different groups of equal size : LED ( λ of 640 ± 20 nm and spatial average energy fluency of 1.2 J/cm2 during hospitalization ) , placebo , or control . The outcomes assessed were pain when coughing by a visual analog scale ( VAS ) and the McGill question naire and sternotomy healing by clinical assessment and photographical register end interpretation . The LED group had better pain reduction , as indicated by both the VAS and the McGill question naire ( number of words chosen and pain index ) ( p ≤ 0.05 ) , on days 6 and 8 after hospital discharge compared to the placebo and control groups . One month after surgery , almost no individual mentioned pain when coughing . Three research ers blindly analyzed the incision photographs to determine hyperemia and wound closure , and they found that the LED group had both less hyperemia and less incision bleeding or dehiscence . The LED therapy ( 640 nm ) had an analgesic effect on the sternotomies of patients who underwent CABG , increasing their incision healing and preventing dehiscence AIMS Exenatide , a glucagon-like-peptide-1 analogue , increases myocardial salvage in experimental setting s with coronary occlusion and subsequent reperfusion . We evaluated the cardioprotective effect of exenatide at the time of reperfusion in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) treated with primary percutaneous coronary intervention ( pPCI ) . METHODS AND RESULTS A total of 172 patients with STEMI and Thrombolysis in Myocardial Infa rct ion flow 0/1 were r and omly assigned to exenatide or placebo ( saline ) intravenously . Study treatment was commenced 15 min before intervention and maintained for 6 h after the procedure . The primary endpoint was salvage index calculated from myocardial area at risk ( AAR ) , measured in the acute phase , and final infa rct size measured 90 ± 21 days after pPCI by cardiac magnetic resonance ( CMR ) . In 105 patients evaluated with CMR , a significantly larger salvage index was found in the exenatide group than in the placebo group ( 0.71 ± 0.13 vs. 0.62 ± 0.16 ; P= 0.003 ) . Infa rct size in relation to AAR was also smaller in the exenatide group ( 0.30 ± 0.15 vs. 0.39 ± 0.15 ; P= 0.003 ) . In a regression analysis , there was a significant correlation between the infa rct size and the AAR for both treatment groups and an analysis of covariance showed that data points in the exenatide group lay significantly lower than for the placebo group ( P= 0.011 ) . There was a trend towards smaller absolute infa rct size in the exenatide group ( 13 ± 9 vs. 17 ± 14 g ; P= 0.11 ) . No difference was observed in left ventricular function or 30-day clinical events . No adverse effects of exenatide were observed . CONCLUSION In patients with STEMI undergoing pPCI , administration of exenatide at the time of reperfusion increases myocardial salvage OBJECTIVE The aim of this study was to investigate if low-level laser therapy ( LLLT ) can modulate acute inflammation and tumor necrosis factor ( TNFalpha ) levels . BACKGROUND DATA Drug therapy with TNFalpha-inhibitors has become st and ard treatment for rheumatoid arthritis , but it is unknown if LLLT can reduce or modulate TNFalpha levels in inflammatory disorders . METHODS Two controlled animal studies were undertaken , with 35 male Wistar rats r and omly divided into five groups each . Rabbit antiserum to ovalbumin was instilled intrabronchially in one of the lobes , followed by the intravenous injection of 10 mg of ovalbumin in 0.5 mL to induce acute lung injury . The first study served to define the time profile of TNFalpha activity for the first 4 h , while the second study compared three different LLLT doses to a control group and a chlorpromazine group at a timepoint where TNFalpha activity was increased . The rats in LLLT groups were irradiated within 5 min at the site of injury by a 650-nm Ga-Al-As laser . RESULTS There was a time-lag before TNFalpha activity increased after BSA injection . TNFalpha levels increased from < or = 6.9 ( 95 % confidence interval [ CI ] , 5.6 - 8.2 ) units/mL in the first 3 h to 62.1 ( 95 % CI , 60.8 - 63.4 ) units/mL ( p < 0.001 ) at 4 h. An LLLT dose of 0.11 Joules administered with a power density of 31.3 mW/cm(2 ) in 42 sec significantly reduced TNFalpha level to 50.2 ( 95 % CI , 49.4 - 51.0 ) , p < 0.01 units/mL versus control . Chlorpromazine reduced TNFalpha level to 45.3 ( 95 % CI , 44.0 - 46.6 ) units/mL , p < 0.001 versus control . CONCLUSION LLLT can reduce TNFalpha expression after acute immunocomplex lung injury in rats , but LLLT dose appears to be critical for reducing TNFalpha release We aim ed to evaluate the effect of melatonin on myo-cardial cell oncosis in the myocardial ischemia/reperfusion injury rat , and the role of the mitochondrial permeability transition pore ( MPTP ) therein . Sprague Dawley rats ( N = 60 ) were r and omly divided into five groups of 12 rats each : control , ischemia/reperfusion ( I/R ) , melatonin treatment ( MT ) , melatonin treatment + atractyloside ( MT+ATR ) , and atractyloside ( ATR ) . We prepared the myocardial ischemia/reperfusion model by reperfusion after the left anterior descending coronary artery was ligated for 30 min . The MT rats were given a 10 mg/kg MT intra-venous injection immediately thereafter ; the MT+ATR rats were also given a 5 mg/kg ATR intravenous injection 15 min before the ischemia ; the ATR rats were given the ATR injection only . After 2-h re-perfusion , myocardial tissue was extracted , the infa rct ion size was determined , and myocardial ultrastructures were observed using electron microscopy . The expression level of the preoncosis receptor ( porimin ) , which can induce membrane injury , was determined by western blot ; the nicotinamide adenine dinucleotide ( NAD(+ ) ) content was determined spectrophotometrically . The four treatment groups showed upregulat-ed expression of myocardial porimin , increased myocardial infa rct ion size , and reduced NAD(+ ) content ( P < 0.05 ) . Compared with the I/R and MT+ATR groups , MT rats showed downregulated expression of myo-cardial porimin , reduced myocardial infa rct size , and increased myo-cardial cell NAD(+ ) content ( P < 0.05 ) . The above indices between the ATR and MT+ATR groups were not significantly different ( P > 0.05 ) . Thus , MT might protect myocardial ischemia/reperfusion rats by inhibiting MPTP opening and reducing myocardial cell oncosis A high restenosis rate remains a limiting factor for coronary angioplasty and stenting . Recently , use of intravascular red light therapy ( IRLT ) has been shown to be effective in different animal models and in humans in reducing the restenosis rate . Sixty-eight patients were treated with IRLT in conjunction with coronary stenting procedures . Mean age was 64 + /- 9 years . Treated lesions were type A ( 11 ) , type B ( 42 ) , and type C ( 18 ) with a mean lesion length of 16.5 + /- 2.4 mm . Reference vessel diameter and minimal lumen diameter ( MLD ) before therapy were 2.90 + /- 0.15 and 1.12 + /- 0.36 mm , respectively . After stenting and laser irradiation , MLD was 2.76 + /- 0.39 mm . No procedural complications or in-hospital adverse events occurred . All patients were followed up as depicted in the protocol . Sixty-one patients underwent angiographic re study , which revealed restenosis in 9 patients ( 14.7 % ) . Observed restenosis rate by artery size was > 3 mm ( n = 21 , 0 % ) , 2.5 to 3.0 mm ( n = 28 , 14.2 % ) , and < 2.5 mm ( n = 12 , 41.6 % ) . We conclude that IRLT is safe and feasible and reduces the expected restenosis rate in patients after coronary stenting in arteries of > 2.5 mm Objective : Exposure to natural sunlight has been associated with improvement in mood , reduced mortality among patients with cancer , and reduced length of hospitalization for patients who have experienced myocardial infa rct ion . Our aim was to evaluate whether the amount of sunlight in a hospital room modifies a patient ’s psychosocial health , the quantity of analgesic medication used , and the pain medication cost . Methods : A prospect i ve study of pain medication use was conducted in 89 patients undergoing elective cervical and lumbar spinal surgery where they were housed on either the “ bright ” or “ dim ” side of the same hospital unit . Analgesic medication was converted to st and ard morphine equivalents for interpatient comparison . The intensity of sunlight in each hospital room was measured daily and psychologic question naires were administered on the day after surgery and at discharge . Results : Patients staying on the bright side of the hospital unit were exposed to 46 % higher-intensity sunlight on average ( p = .005 ) . Patients exposed to an increased intensity of sunlight experienced less perceived stress ( p = .035 ) , marginally less pain ( p = .058 ) , took 22 % less analgesic medication per hour ( p = .047 ) , and had 21 % less pain medication costs ( p = .047 ) . Age quartile was the only other variable found to be a predictor of analgesic use , with a significant negative correlation ( p < .001 ) . However , patients housed on the bright side of the hospital consistently used less analgesic medications in all age quartiles . Conclusion : The exposure postoperatively of patients who have undergone spinal surgery to increased amounts of natural sunlight during their hospital recovery period may result in decreased stress , pain , analgesic medication use , and pain medication costs . ACCF = anterior cervical corpectomy and fusion ; ACDF = anterior cervical discectomy and fusion ; AEDET = Achieving Excellence Design Evaluation Toolkit ; CES-D = Center for Epidemiological Studies –Depression Scale ; CNS = central nervous system ; DS = degenerative spondylolisthesis ; LOS = length of stay ; LOT-R = Life Orientation Test-Revised ; LS = lumbar stenosis ; MPQ = McGill Pain Question naire ; OR = operating room ; PACU = postanesthesia care unit ; PCA = patient-controlled analgesia ; PFI = Private Finance Initiative ; POMS = Reduced POMS – Anxiety Scale ; PRN = as needed ; PSS = Perceived Stress Scale ; SAD = seasonal affective disorder ; TCAs = tricyclic antidepressants ; UK = United Kingdom BACKGROUND AND OBJECTIVE A high restenosis rate remains a limiting factor for percutaneous transluminal coronary angioplasty and stenting . The objective of this study was to evaluate the effect of intravascular red laser therapy ( IRLT ) on restenosis after stenting procedures in de novo lesions . STUDY DESIGN / MATERIAL S AND METHODS A total of 68 consecutive patients were treated with IRLT in conjunction with coronary stenting procedures . Mean lesion length was 16.5 + /- 2.4 mm . Reference vessel diameter ( RVD ) and pre-minimal lumen diameter ( MLD ) were 2.90 + /- 0.15 mm and 1.12 + /- 0.26 mm , respectively . RESULTS After treatment , MLD was 2.76 + /- 0.32 mm with no procedural complications or in-hospital adverse events . Angiographic follow-up ( n = 61 ) revealed restenosis in nine patients ( 14.7 % ) with rate by artery size of > 3 mm ( n = 21 ) 0 % ; 2.5 - -3.0 mm ( n = 28 ) 14.2 % ; and < 2.5 mm ( n = 12 ) 41.6 % . CONCLUSION Intravascular red light therapy is safe , feasible , and reduces expected restenosis rate after coronary stenting BACKGROUND AND OBJECTIVE Muscle regeneration is a complex phenomenon , involving coordinated activation of several cellular responses . During this process , oxidative stress and consequent tissue damage occur with a severity that may depend on the intensity and duration of the inflammatory response . Among the therapeutic approaches to attenuate inflammation and increase tissue repair , low-level laser therapy ( LLLT ) may be a safe and effective clinical procedure . The aim of this study was to evaluate the effects of LLLT on oxidative/nitrative stress and inflammatory mediators produced during a cryolesion of the tibialis anterior ( TA ) muscle in rats . MATERIAL AND METHODS Sixty Wistar rats were r and omly divided into three groups ( n = 20 ) : control ( BC ) , injured TA muscle without LLLT ( IC ) , injured TA muscle su bmi tted to LLLT ( IRI ) . The injured region was irradiated daily for 4 consecutive days , starting immediately after the lesion using a AlGaAs laser ( continuous wave , 808 nm , tip area of 0.00785 cm(2 ) , power 30 mW , application time 47 seconds , fluence 180 J/cm(2 ) ; 3.8 mW/cm(2 ) ; and total energy 1.4 J ) . The animals were sacrificed on the fourth day after injury . RESULTS LLLT reduced oxidative and nitrative stress in injured muscle , decreased lipid peroxidation , nitrotyrosine formation and NO production , probably due to reduction in iNOS protein expression . Moreover , LLLT increased SOD gene expression , and decreased the inflammatory response as measured by gene expression of NF-kβ and COX-2 and by TNF-α and IL-1β concentration . CONCLUSION These results suggest that LLLT could be an effective therapeutic approach to modulate oxidative and nitrative stress and to reduce inflammation in injured muscle OBJECTIVES Low-level laser irradiation ( LLLI ) has the potential of exerting cardioprotective effect following myocardial infa rct ion ( MI ) . The authors hypothesized that LLLI could influence the expression of cardiac cytokines and contribute to the reversal of ventricular remodeling . BACKGROUND LLLI regulates the expression of cytokines after tissue damage . However , little is known concerning the alteration of the cardiac cytokine expression profile after LLLI . METHODS MI was created by coronary ligation . The surviving rats were divided r and omly into laser and control groups . 33 rats were exposed to a diode laser ( 635 nm , 5 mW , CW , laser , beam spot size 0.8 cm(2 ) , 6 mW/cm(2 ) , 150 sec , 0.8 J , 1J/cm(2 ) ) as laser group . Another 33 rats received only coronary ligation and served as control group . 28 rats received a thoracotomy without coronary ligation ( sham group ) . One day after laser irradiation , 5 rats from each group were sacrificed and the heart tissues were analyzed by cytokine antibody arrays . Enzyme-linked immunosorbent assay ( ELISA ) was performed to confirm its reliability . Two weeks after MI , cardiac function and structure were evaluated by echocardiography and histological study . RESULTS Cytokine antibody array indicated 4 cytokines were significantly changed after laser therapy . ELISA confirmed that granulocyte-macrophage colony stimulating factor and fractalkine were the cytokines involved in the response to therapeutic laser irradiation . However , there was no difference in cytokine release between various groups at 2 weeks after MI . Although LLLI did not improve the damaged heart function , it did reduce the infa rct area expansion . CONCLUSIONS The antibody-based protein array technology was applied for screening the cytokine expression profile following MI , with or without laser irradiation . The expression of multiple cytokines was regulated in the acute phase after LLLI . Our results revealed a potential novel mechanism for applying laser therapy to the treatment of heart disease Background Systematic Review s ( SRs ) of experimental animal studies are not yet common practice , but awareness of the merits of conducting such SRs is steadily increasing . As animal intervention studies differ from r and omized clinical trials ( RCT ) in many aspects , the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies . The Cochrane Collaboration developed a Risk of Bias ( RoB ) tool to establish consistency and avoid discrepancies in assessing the method ological quality of RCTs . A similar initiative is warranted in the field of animal experimentation . Methods We provide an RoB tool for animal intervention studies ( SYRCLE ’s RoB tool ) . This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies . To enhance transparency and applicability , we formulated signalling questions to facilitate judgment . Results The result ing RoB tool for animal studies contains 10 entries . These entries are related to selection bias , performance bias , detection bias , attrition bias , reporting bias and other biases . Half these items are in agreement with the items in the Cochrane RoB tool . Most of the variations between the two tools are due to differences in design between RCTs and animal studies . Shortcomings in , or unfamiliarity with , specific aspects of experimental design of animal studies compared to clinical studies also play a role . Conclusions SYRCLE ’s RoB tool is an adapted version of the Cochrane RoB tool . Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies . This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the method ological quality of animal studies |
2,226 | 24,386,988 | Conclusions This review highlights the weak evidence base on ACT adherence .
Results suggest that ACT adherence levels varied substantially between study population s , but comparison between studies was challenging due to differences in study design , definitions , and methods used to measure adherence . | Background Increasing access to and targeting of artemisinin-based combination therapy ( ACT ) is a key component of malaria control programmes .
To maximize efficacy of ACT and ensure adequate treatment outcomes , patient and caregiver adherence to treatment guidelines is essential .
This review summarizes the current evidence base on ACT adherence , including definitions , measurement methods , and associated factors . | Background Home-management of malaria ( HMM ) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa . However , limited data are available on the effectiveness of using artemisinin-based combination therapy ( ACT ) within the HMM strategy . The aim of this study was to assess the effectiveness of artemether-lumefantrine ( AL ) , presently the most favoured ACT in Africa , in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania , when provided by community health workers ( CHWs ) and administered unsupervised by parents or guardians at home . Methods An open label , single arm prospect i ve study was conducted in two rural villages with high malaria transmission in Kibaha District , Tanzania . Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test ( RDT ) were provisionally enrolled and provided AL for unsupervised treatment at home . Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and review ed weekly by the CHWs during 42 days . Primary outcome measure was PCR corrected parasitological cure rate by day 42 , as estimated by Kaplan-Meier survival analysis . This trial is registered with Clinical Trials.gov , number NCT00454961 . Results A total of 244 febrile children were enrolled between March-August 2007 . Two patients were lost to follow up on day 14 , and one patient withdrew consent on day 21 . Some 141/241 ( 58.5 % ) patients had recurrent infection during follow-up , of whom 14 had recrudescence . The PCR corrected cure rate by day 42 was 93.0 % ( 95 % CI 88.3%-95.9 % ) . The median lumefantrine concentration was statistically significantly lower in patients with recrudescence ( 97 ng/mL [ IQR 0 - 234 ] ; n = 10 ) compared with reinfections ( 205 ng/mL [ 114 - 390 ] ; n = 92 ) , or no parasite reappearance ( 217 [ 121 - 374 ] ng/mL ; n = 70 ; p ≤ 0.046 ) . Conclusions Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective , which provides evidence base for scaling-up implementation of HMM with AL in Tanzania BACKGROUND Between 1995 and 2000 , KwaZulu-Natal province , South Africa , experienced a marked increase in Plasmodium falciparum malaria , fuelled by pyrethroid and sulfadoxine-pyrimethamine resistance . In response , vector control was strengthened and artemether-lumefantrine ( AL ) was deployed in the first Ministry of Health artemisinin-based combination treatment policy in Africa . In South Africa , effective vector and parasite control had historically ensured low-intensity malaria transmission . Malaria is diagnosed definitively and treatment is provided free of charge in reasonably accessible public-sector health-care facilities . METHODS AND FINDINGS We review ed four years of malaria morbidity and mortality data at four sentinel health-care facilities within KwaZulu-Natal 's malaria-endemic area . In the year following improved vector control and implementation of AL treatment , malaria-related admissions and deaths both declined by 89 % , and outpatient visits decreased by 85 % at the sentinel facilities . By 2003 , malaria-related outpatient cases and admissions had fallen by 99 % , and malaria-related deaths had decreased by 97 % . There was a concomitant marked and sustained decline in notified malaria throughout the province . No serious adverse events were associated causally with AL treatment in an active sentinel pharmacovigilance survey . In a prospect i ve study with 42 d follow up , AL cured 97/98 ( 99 % ) and prevented gametocyte developing in all patients . Consistent with the findings of focus group discussion s , a household survey found self-reported adherence to the six-dose AL regimen was 96 % . CONCLUSION Together with concurrent strengthening of vector control measures , the antimalarial treatment policy change to AL in KwaZulu-Natal contributed to a marked and sustained decrease in malaria cases , admissions , and deaths , by greatly improving clinical and parasitological cure rates and reducing gametocyte carriage Background The Home Management of Malaria ( HMM ) strategy was developed using chloroquine , a now obsolete drug , which has been replaced by artemisinin-based combination therapy ( ACT ) in health facility setting s. Incorporation of ACT in HMM would greatly exp and access to effective antimalarial therapy by the population s living in underserved areas in malaria endemic countries . The feasibility and acceptability of incorporating ACT in HMM needs to be evaluated . Methods A multi-country study was performed in four district-size sites in Ghana ( two sites ) , Nigeria and Ug and a , with population s ranging between 38,000 and 60,000 . Community medicine distributors ( CMDs ) were trained in each village to dispense pre-packaged ACT to febrile children aged 6–59 months , after exclusion of danger signs . A community mobilization campaign accompanied the programme . Artesunate-amodiaquine ( AA ) was used in Ghana and artemether-lumefantrine ( AL ) in Nigeria and Ug and a. Harmonized qualitative and quantitative data collection methods were used to evaluate CMD performance , caregiver adherence and treatment coverage of febrile children with ACTs obtained from CMDs . Results Some 20,000 fever episodes in young children were treated with ACT by CMDs across the four study sites . Cross-sectional surveys identified 2,190 children with fever in the two preceding weeks , of whom 1,289 ( 59 % ) were reported to have received ACT from a CMD . Coverage varied from 52 % in Nigeria to 75 % in Ho District , Ghana . Coverage rates did not appear to vary greatly with the age of the child or with the educational level of the caregiver . A very high proportion of children were reported to have received the first dose on the day of onset or the next day in all four sites ( range 86–97 % , average 90 % ) . The proportion of children correctly treated in terms of dose and duration was also high ( range 74–97 % , average 85 % ) . Overall , the proportion of febrile children who received prompt treatment and the correct dose for the assigned duration of treatment ranged from 71 % to 87 % ( average 77 % ) . Almost all caregivers perceived ACT to be effective , and no severe adverse events were reported . Conclusion ACTs can be successfully integrated into the HMM strategy OBJECTIVE To examine the extent to which district health teams could reduce the burden of malaria , a continuing major cause of mortality and morbidity , in a situation where severe re source constraints existed and integrated care was provided . METHODS Antimalarial drugs were prepackaged into unit doses in an attempt to improve compliance with full courses of chemotherapy . FINDINGS Compliance improved by approximately 20 % in both adults and children . There were 50 % reductions in cost to patients , waiting time at dispensaries and drug wastage at facilities . The intervention , which tended to improve both case and drug management at facilities , was well accepted by health staff and did not involve them in additional working time . CONCLUSION The prepackaging of antimalarials at the district level offers the prospect of improved compliance and a reduction in the spread of resistance A r and omized , controlled , malaria-clinic-based field trial was conducted to compare compliance with a 7-day quinine + tetracycline regimen and a 5-day 700-mg artesunate regimen for the treatment of uncomplicated falciparum malaria in a community in Thail and . Of 137 patients , aged 15 - 60 years attending a malaria clinic , 77 received artesunate and 60 received quinine + tetracycline . Compliance and cure rates were evaluated on days 5 ( artesunate ) and 7 ( quinine + tetracycline ) using patient interview/residual pill counts and peripheral blood smear , respectively . Data were analysed using the intention-to-treat approach , and the reasons for compliance and noncompliance were investigated . Compliance was significantly higher ( 98.4 % ) with artesunate than with quinine + tetracycline ( 71.7 % ) ( relative risk adjusted for sex ( aRR ) = 1.39 ( 95 % C.I. = 1.15 - 1.68 ) ; referent : quinine + tetracycline ) . Cure rate ( 100 % ) was higher in those receiving artesunate than quinine + tetracycline ( 77.4 % ) ( aRR = 1.32 ( 95 % C.I. = 1.12 - 1.55 ) ) . Reasons for compliance included the desire to be cured and to follow the advice of malaria staff/employer , and the simple dosing regimen . Noncompliance was mostly due to adverse reactions and forgetting to take the drugs . These results can serve as a baseline for design ing and evaluating new interventions to improve compliance , as well as for study ing cost-effectiveness to help drug policy decision-making . We recommend a strategy which integrates a short-course , once-a-day regimen ( with minimal adverse reactions ) , a better delivery system for antimalarial drugs and health education , and an enhanced advisory role of malaria staff . Considering the higher compliance rate and curative effectiveness of artesunate , we recommend its use instead of quinine + tetracycline for the treatment of uncomplicated malaria in clinics in Thail and Background Over the years , reports implicate improper anti-malarial use as a major contributor of morbidity and mortality amongst millions of residents in malaria endemic areas , Kenya included . However , there are limited reports on improper use of Artemisinin-based Combination Therapy ( ACT ) which is a first-line drug in the treatment of malaria in Kenya . Knowing this is important for ensured sustainable cure rates and also protection against the emergence of resistant malarial parasites . We therefore investigated ACT adherence level , factors associated with non-adherence and accessibility in households ( n = 297 ) in rural location of Southeast Alego location in Siaya County in western Kenya . Methods ACT Adherence level was assessed with reference to the duration of treatment and number of tablets taken . Using systematic r and om sampling technique , a question naire was administered to a particular household member who had the most recent malaria episode ( < 2 weeks ) and used ACT for cure . Parents/caretakers provided information for children aged < 13 years . Key Informant Interviews ( KIIs ) were also conducted with healthcare providers and private dispensing chemist operators . Results Adherence to ACT prescription remained low at 42.1 % and 57.9 % among individuals above 13 and less than 13 years , respectively . Stratification by demographic and socio-economic characteristics in relation to ACT adherence revealed that age ( P = 0.011 ) , education level ( P < 0.01 ) , ability to read ( P < 0.01 ) and household ( HH ) monthly income ( P = 0.002 ) significantly affected the level of ACT adherence . Consistently , logistic regression model demonstrated that low age ( OR , 0.571 , 95 % CI , 0.360 - 0.905 ; P = 0.017 ) , higher education level ( OR , 0.074 ; 95 % CI 0.017 - 0.322 ; P < 0.01 ) , ability to read ( OR , 0.285 , 95 % CI , 0.167 - 0.486 ; P < 0.01 ) and higher income ( Ksh . > 9000 ; OR , 0.340 ; 95 % CI , 0.167 - 0.694 ; P = 0.003 ) were associated with ACT adherence . In addition , about 52.9 % of the respondents reported that ACT was not always available at the source and that drug availability ( P = 0.020 ) and distance to drug source ( P < 0.01 ) significantly affected accessibility . Conclusions This study demonstrates that more than half of those who get ACT prescription do not take recommended dose and that accessibility is of concern . The findings of this study suggest a potential need to improve accessibility and also initiate programmatic interventions to encourage patient-centred care BACKGROUND Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease . There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border , historically a site of emerging antimalarial-drug resistance . METHODS In two open-label , r and omized trials , we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin , western Cambodia , and Wang Pha , northwestern Thail and : oral artesunate given at a dose of 2 mg per kilogram of body weight per day , for 7 days , and artesunate given at a dose of 4 mg per kilogram per day , for 3 days , followed by mefloquine at two doses totaling 25 mg per kilogram . We assessed in vitro and in vivo Plasmodium falciparum susceptibility , artesunate pharmacokinetics , and molecular markers of resistance . RESULTS We studied 40 patients in each of the two locations . The overall median parasite clearance times were 84 hours ( interquartile range , 60 to 96 ) in Pailin and 48 hours ( interquartile range , 36 to 66 ) in Wang Pha ( P<0.001 ) . Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients ( 30 % ) receiving artesunate monotherapy and 1 of 20 ( 5 % ) receiving artesunate-mefloquine therapy in Pailin , as compared with 2 of 20 ( 10 % ) and 1 of 20 ( 5 % ) , respectively , in Wang Pha ( P=0.31 ) . These markedly different parasitologic responses were not explained by differences in age , artesunate or dihydroartemisinin pharmacokinetics , results of isotopic in vitro sensitivity tests , or putative molecular correlates of P. falciparum drug resistance ( mutations or amplifications of the gene encoding a multidrug resistance protein [ PfMDR1 ] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [ PfSERCA ] ) . Adverse events were mild and did not differ significantly between the two treatment groups . CONCLUSIONS P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thail and . Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing . Containment measures are urgently needed . ( Clinical Trials.gov number , NCT00493363 , and Current Controlled Trials number , IS RCT N64835265 . Background Chlorproguanil-dapsone ( Lapdap ) , developed as a low-cost antimalarial , was withdrawn in 2008 after concerns about safety in G6PD deficient patients . This trial was conducted in 2004 to evaluate the safety and effectiveness of CD and comparison with artemether-lumefantrine ( AL ) under conditions of routine use in G6PD normal and G6PD deficient patients with uncomplicated malaria in The Gambia . We also examined the effects of a common genetic variant that affects chlorproguanil metabolism on risk of treatment failure . Methods 1238 children aged 6 months to 10 years with uncomplicated malaria were r and omized to receive CD or artemether-lumefantrine ( AL ) and followed for 28 days . The first dose was supervised , subsequent doses given unsupervised at home . G6PD genotype was determined to assess the interaction between treatment and G6PD status in their effects on anaemia . The main endpoints were clinical treatment failure by day 28 , incidence of severe anaemia ( Hb<5 g/dL ) , and haemoglobin concentration on day 3 . Findings One third of patients treated with AL , and 6 % of patients treated with CD , did not complete their course of medication . 18 % ( 109/595 ) of children treated with CD and 6.1 % ( 36/587 ) with AL required rescue medication within 4 weeks , risk difference 12 % ( 95%CI 8.9%–16 % ) . 23 children developed severe anaemia ( 17 ( 2.9 % ) treated with CD and 6 ( 1.0 % ) with AL , risk difference 1.8 % , 95%CI 0.3%–3.4 % , P = 0.02 ) . Haemoglobin concentration on day 3 was lower among children treated with CD than AL ( difference 0.43 g/dL , 95 % CI 0.24 to 0.62 ) , and within the CD group was lower among those children who had higher parasite density at enrolment . Only 17 out of 1069 children who were typed were G6PD A- deficient , of these 2/9 treated with CD and 1/8 treated with AL developed severe anaemia . 5/9 treated with CD had a fall of 2 g/dL or more in haemoglobin concentration by day 3 . Interpretation AL was well tolerated and highly effective and when given under operational conditions despite poor adherence to the six-dose regimen . There were more cases of severe malaria and anaemia after CD treatment although G6PD deficiency was uncommon . Trial Registration Clinical trials.gov Background Sulphadoxine-pyrimethamine ( SP ) is the only single dose therapy for uncomplicated malaria , but there is widespread resistance . At the time of this study , artemether-lumefantrine ( AL ) and chlorproguanil-dapsone ( CPD ) , both multi-dose regimes , were considered possible alternatives to SP in Malawi . The aim of this study was to investigate the impact of poor adherence on the effectiveness of AL and CPD . Methods Children ≥12 months and adults with uncomplicated malaria were r and omized to receive AL , CPD or SP . Adherence was measured using a question naire and electronic monitoring devices , MEMS ™ , pill bottles that recorded the date and time of opening . Day-7 plasma dapsone or lumefantrine concentrations were measured to examine their relationship with adherence and clinical response . Results 841 patients were recruited . The day-28 adequate clinical and parasitological response ( ACPR ) rates , using intention to treat analysis ( missing data treated as failure ) , were AL 85.2 % , CPD 63.7 % and SP 50 % . ACPR rates for AL were higher than CPD or SP on days 28 and 42 ( p ≤ 0.002 for all comparisons ) . CPD was more effective than SP on day-28 ( p = 0.01 ) , but not day-42.Very high adherence was reported using the question naire , 100 % for AL treated patients and 99.2 % for the CPD group . Only three CPD participants admitted missing any doses . 164/181 ( 90.6 % ) of CPD treated patients took all their doses out of the MEMS ™ container and they were more likely to have a day-28 ACPR than those who did not take all their medication out of the container , p = 0.024 . Only 7/87 ( 8 % ) AL treated patients did not take all of their doses out of their MEMS ™ container and none had treatment failure . Median day-7 dapsone concentrations were higher in CPD treated patients with ACPR than in treatment failures , p = 0.012 . There were no differences in day-7 dapsone or lumefantrine concentrations between those who took all their doses from the MEMS ™ container and those who did not . A day-7 lumefantrine concentration reported to be predictive of AL treatment failure in Thail and was not useful in this population ; only one of 16 participants with a concentration below this threshold ( 175 ng/ml ) had treatment failure . Conclusion This study provides reassurance of the effectiveness of AL , even with unsupervised dosing , as it is rolled out across sub-Saharan Africa . Self-reported adherence appears to be an unreliable measure of adherence in this population Introduction . To enhance effective treatment , african nations including Ghana changed its malaria treatment policy from monotherapy to combination treatment with artesunate-amodiaquine ( AS+AQ ) . The major challenge to its use in loose form is adherence . Objective . The objectives of this study were to investigate adherence and treatment outcome among patients treated with AS+AQ combination therapy for acute uncomplicated malaria . Methodology . The study was conducted in two rural districts located in the middle belt of Ghana using quantitative methods . Patients diagnosed with acute uncomplicated malaria as per the Ghana Ministry of Health malaria case definitions were r and omly allocated to one of two groups . All patients in both groups were educated about the dose regimen of AS+AQ therapy and the need for adherence . Treatment with AS+AQ was supervised in one group while the other group was not supervised . Adherence was assessed by direct observation of the blister package of AS+AQ left on day 2 . Results . 401 participants were r and omized into the supervised ( 211 ) and unsupervised ( 190 ) groups . Compliance in both supervised ( 95.7 % ) and unsupervised ( 92.6 % ) groups were similar ( P = .18 ) . The commonest side-effects reported on day 2 among both groups were headaches , and body weakness . Parasite clearance by day 28 was > 95 % in both groups . Discussion / Conclusions . Administration of AS-AQ in both groups result ed in high levels of adherence to treatment regimen among adolescent and adult population in central Ghana . It appears that high level of adherence to AS-AQ is achievable through a rigorous education programme during routine clinic visits Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials Objective To compare the effectiveness of oral quinine with that of artemether-lumefantrine in treating uncomplicated malaria in children . Design R and omised , open label effectiveness study . Setting Outpatient clinic of Ug and a ’s national referral hospital in Kampala . Participants 175 children aged 6 to 59 months with uncomplicated malaria . Interventions Participants were r and omised to receive oral quinine or artemether-lumefantrine administered by care givers at home . Main outcome measures Primary outcomes were parasitological cure rates after 28 days of follow-up unadjusted and adjusted by genotyping to distinguish recrudescence from new infections . Secondary outcomes were adherence to study drug , presence of gametocytes , recovery of haemoglobin concentration from baseline at day 28 , and safety profiles . Results Using survival analysis the cure rate unadjusted by genotyping was 96 % for the artemether-lumefantrine group compared with 64 % for the quinine group ( hazard ratio 10.7 , 95 % confidence interval 3.3 to 35.5 , P=0.001 ) . In the quinine group 69 % ( 18/26 ) of parasitological failures were due to recrudescence compared with none in the artemether-lumefantrine group . The mean adherence to artemether-lumefantrine was 94.5 % compared with 85.4 % to quinine ( P=0.0008 ) . Having adherence levels of 80 % or more was associated with a decreased risk of treatment failure ( 0.44 , 0.19 to 1.02 , P=0.06 ) . Adverse events did not differ between the two groups . Conclusions The effectiveness of a seven day course of quinine for the treatment of uncomplicated malaria in Ug and an children was significantly lower than that of artemether-lumefantrine . These findings question the advisability of the recommendation for quinine therapy for uncomplicated malaria in Africa . Trial registration Clinical Trials.gov NCT00540202 BACKGROUND Artemisinin-based combinations are judged the best treatments for multidrug-resistant Plasmodium falciparum malaria . Artesunate-mefloquine is widely recommended in southeast Asia , but its high cost and tolerability profile remain obstacles to widespread deployment . To assess whether dihydroartemisinin-piperaquine is a suitable alternative to artesunate-mefloquine , we compared the safety , tolerability , efficacy , and effectiveness of the two regimens for the treatment of uncomplicated falciparum in western Myanmar ( Burma ) . METHODS We did an open r and omised comparison of 3-day regimens of artesunate-mefloquine ( 12/25 mg/kg ) versus dihydroartemisinin-piperaquine ( 6.3/50 mg/kg ) for the treatment of children aged 1 year or older and in adults with uncomplicated falciparum malaria in Rakhine State , western Myanmar . Within each group , patients were r and omly assigned supervised or non-supervised treatment . The primary endpoint was the PCR-confirmed parasitological failure rate by day 42 . Failure rates at day 42 were estimated by Kaplan-Meier survival analysis . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N27914471 . FINDINGS Of 652 patients enrolled , 327 were assigned dihydroartemisinin-piperaquine ( 156 supervised and 171 not supervised ) , and 325 artesunate-mefloquine ( 162 and 163 , respectively ) . 16 patients were lost to follow-up , and one patient died 22 days after receiving dihydroartemisinin-piperaquine . Recrudescent parasitaemias were confirmed in only two patients ; the day 42 failure rate was 0.6 % ( 95 % CI 0.2 - 2.5 ) for dihydroartemisinin-piperaquine and 0 ( 0 - 1.2 ) for artesunate-mefloquine . Whole-blood piperaquine concentrations at day 7 were similar for patients with observed and non-observed dihydroartemisinin-piperaquine treatment . Gametocytaemia developed more frequently in patients who had received dihydroartemisinin-piperaquine than in those on artesunate-mefloquine : day 7 , 18 ( 10 % ) of 188 versus five ( 2 % ) of 218 ; relative risk 4.2 ( 1.6 - 11.0 ) p=0.011 . INTERPRETATION Dihydroartemisinin-piperaquine is a highly efficacious and inexpensive treatment of multidrug-resistant falciparum malaria and is well tolerated by all age groups . The effectiveness of the unsupervised treatment , as in the usual context of use , equalled its supervised efficacy , indicating good adherence without supervision . Dihydroartemisinin-piperaquine is a good alternative to artesunate-mefloquine Background Early diagnosis and prompt , effective treatment of uncomplicated malaria is critical to prevent severe disease , death and malaria transmission . We assessed the impact of rapid malaria diagnostic tests ( RDTs ) by community health workers ( CHWs ) on provision of artemisinin-based combination therapy ( ACT ) and health outcome in fever patients . Methodology /Principal Findings Twenty-two CHWs from five villages in Kibaha District , a high-malaria transmission area in Coast Region , Tanzania , were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis ( CD ) only . Each CHW was r and omly assigned to use either RDT or CD the first week and thereafter alternating weekly . Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7 . The CHWs enrolled 2930 fever patients during five months of whom 1988 ( 67.8 % ) presented within 24 hours of fever onset . ACT was provided to 775 of 1457 ( 53.2 % ) patients during RDT weeks and to 1422 of 1473 ( 96.5 % ) patients during CD weeks ( Odds Ratio ( OR ) 0.039 , 95 % CI 0.029–0.053 ) . The CHWs adhered to the RDT results in 1411 of 1457 ( 96.8 % , 95 % CI 95.8–97.6 ) patients . More patients were referred on inclusion day during RDT weeks ( 10.0 % ) compared to CD weeks ( 1.6 % ) . Referral during days 1–7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis . However , no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT , supporting the safety of withholding ACT to RDT negative patients . Conclusions / Significance RDTs in the h and s of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa . Trial registration Clinical Trials.gov Background Increasing affordability of artemisinin combination therapy ( ACT ) in the African retail sector could be critical to exp and ing access to effective malaria treatment , but must be balanced by efforts to protect the efficacy of these drugs . Previous research estimates ACT adherence rates among public sector patients , but adherence among retail sector purchasers could differ substantially . This study aim ed to estimate adherence rates to subsidized , over-the-counter ACT in rural Ug and a. Methods An intervention study was conducted with four licensed drug shops in Eastern Ug and a in December 2009 . Artemether-lumefantrine ( AL ) was made available for sale at a 95 % subsidy over-the counter . Customers completed a brief survey at the time of purchase and then were r and omly assigned to one of three study arms : no follow-up , follow-up after two days or follow-up after three days . Surveyors recorded the number of pills remaining through blister pack observation or through self-report if the pack was unavailable . The purpose of the three-day follow-up arm was to capture non-adherence in the sense of an incomplete treatment course ( " under-dosing " ) . The purpose of the two-day follow-up arm was to capture whether participants completed the full course too soon ( " over-dosing " ) . Results Of the 106 patients in the two-day follow-up sample , 14 ( 13.2 % ) had finished the entire treatment course by the second day . Of the 152 patients in the three-day follow-up sample , 49 ( 32.2 % ) were definitely non-adherent , three ( 2 % ) were probably non-adherent and 100 ( 65.8 % ) were probably adherent . Among the 52 who were non-adherent , 31 ( 59.6 % ) had more than a full day of treatment remaining . Conclusions Overall , adherence to subsidized ACT purchased over-the-counter was found to be moderate . Further , a non-trivial fraction of those who complete treatment are taking the full course too quickly . Strategies to increase adherence in the retail sector are needed in the context of increasing availability and affordability of ACT in this sector Background Controlled clinical trials have shown that a six-dose regimen of artemether-lumefantrine ( AL ) therapy for uncomplicated Plasmodium falciparum malaria results in cure rates > 95 % with good tolerability . Material s and methods A prospect i ve study was carried out to document the adherence to and acceptability of AL administration . This was undertaken in the context of the ALIVE study , a prospect i ve , community-based , observational study in a rural , malaria-endemic area of Tanzania . Following microscopic confirmation of P. falciparum infection , the first AL dose was taken under supervision , with the subsequent five doses taken unsupervised at home . Patients were r and omized to receive a home-based assessment close to the scheduled time for one of the unsupervised doses , but were blinded to which follow-up visit they had been allocated . A structured question naire was administered by trained staff and AL consumption was confirmed by inspection of blister packs . Results A total of 552 patients were recruited of whom 352 ( 63.8 % ) were < 13 years old . The r and omization process allocated 112 , 109 , 110 , 100 and 111 patients to a follow-up visit after doses 2 , 3 , 4 , 5 and 6 , respectively . For dose 2 , 92.0 % of patients ( 103/112 ) correctly took AL at 8 ± 1 hours after dose 1 . The remaining doses were taken within four hours of the correct time in 87 - 95 % of cases . Nine patients ( 1.7 % ) missed one dose . Blister packs were available for inspection in 548 of cases ( 99.3 % ) and confirmed patient-reported data that the previous dose had been administered . Nearly all patients took AL with water ( 549/552 [ 99.5 % ] ) . Two patients ( 0.4 % ) took the drug with food . The dosing pictogram and clustering of tablets within the blister packs was considered helpful by 91.8 % and 100.0 % of patients , respectively . Overall , 87.1 % of patients ( 481/552 ) found AL easier to take/administer than sulphadoxine-pyrimethamine ( SP ) and 87.7 % ( 484/552 ) believed that AL was more effective than SP . Discussion Factors contributing to adherence were likely to be helpful packaging , pictorial dosing instructions and patients ' conviction that AL is effective . Conclusion Adherence to the dosing regimen and timing of AL administration was very good As artemether/lumefantrine is now deployed as the first-line treatment for uncomplicated falciparum malaria in Bangladesh , information on its efficacy and adherence to its use is important . A r and omised controlled non-inferiority trial comparing directly observed treatment ( DOT ) and non-directly observed treatment ( NDOT ) was conducted in 320 patients with uncomplicated falciparum malaria in B and arban Hill Tract District , Bangladesh . Both regimens showed similar high levels of PCR-corrected 42-day parasitological and clinical cure rates ( 99.3 % in the NDOT group and 100 % in the DOT group ; P=0.49 ) . Survival analysis for the time to recurrence of infection showed no difference between treatment groups ( log rank , P=0.98 ) . Adherence , as assessed by counting remaining tablets and oral interviews , was 93 % in the NDOT group and was confirmed by Day 7 lumefantrine concentrations . Adherence was independent of educational level . Patients with plasma lumefantrine concentrations < 280 ng/ml at Day 7 were at greater risk for re-infection ( relative risk 5.62 ; P=0.027 ) . The efficacy of artemether/lumefantrine for the treatment of uncomplicated falciparum malaria in Bangladesh is high and is similar for DOT and NDOT . Adherence to therapy is high In a cluster r and omized trial , Beth Kangwana and colleagues find that provision of subsidized packs of the malaria therapy artemether-lumefantrine to shops more than doubled the proportion of children with fever who received drugs promptly Background Development of resistance to first line antimalarials led to recommendation of artemisinin based combination therapies ( ACTs ) . High adherence to ACTs provided by community health workers ( CHWs ) gave reassurance that community based interventions did not increase the risk of drug resistance . Integrated community case management of illnesses ( ICCM ) is now recommended through which children will access both antibiotics and antimalarials from CHWs . Increased number of medicines has been shown to lower adherence . Objective To compare adherence to antimalarials alone versus antimalarials combined with antibiotics under ICCM in children less than five years . Methods A cohort study was nested within a cluster r and omized trial that had CHWs treating children less than five years with antimalarials and antibiotics ( intervention areas ) and CHWs treating children with antimalarials only ( control areas ) . Children were consecutively sample d from the CHWs ' registers in the control areas ( 667 children ) ; and intervention areas ( 323 taking antimalarials only and 266 taking antimalarials plus antibiotics ) . The sample d children were visited at home on day one and four of treatment seeking . Adherence was assessed using self reports and pill counts . Results Adherence in the intervention arm to antimalarials alone and antimalarials plus antibiotics arm was similar ( mean 99 % in both groups ) but higher than adherence in the control arm ( antimalarials only ) ( mean 96 % ) . Forgetfulness ( 38 % ) was the most cited reason for non-adherence . At adjusted analysis : absence of fever ( OR = 3.3 , 95%CI = 1.6–6.9 ) , seeking care after two or more days ( OR = 2.2 , 95%CI = 1.3–3.7 ) , not underst and ing instructions given ( OR = 24.5 , 95%CI = 2.7–224.5 ) , vomiting ( OR = 2.6 , 95%CI = 1.2–5.5 ) , and caregivers ' perception that the child 's illness was not severe ( OR = 2.0 , 95%CI = 1.1–3.8 ) were associated with non-adherence . Conclusions Addition of antibiotics to antimalarials did not lower adherence . However , caregivers should be adequately counseled to underst and the dosing regimens ; continue with medicines even when the child seems to improve ; and re-administer doses that have been vomited Three studies were carried out to determine the need , acceptability , and efficacy of adding mefloquine to artemisinin derivatives ( AD ) for the first-line treatment of uncomplicated falciparum malaria . The first was a retrospective study of 255 basic health workers which showed that their recommendation of AD to patients depended on their level of training . None of the paramedics/midwives and only 9 % of 129 doctors had prescribed AD , and no one had recommended AD in combination with mefloquine ; 72 % of patients used courses that were too short for parasitological cure . To promote the addition of mefloquine to AD regimens we conducted intervention workshops with health care providers and subsidized the cost of mefloquine to patients . In the second study , we interviewed 200 patients before and after the intervention to evaluate drug compliance with full doses of AD and use of subsidized mefloquine . After the intervention , we found that only 3.6 % had used mefloquine and 62 % had taken non-curative doses of AD . In the third study , we provided blister packs of medication in daily doses and compared the intake of AD + placebo ( 158 patients ) with that of AD + mefloquine ( 222 patients ) for 5 days . The compliance with both regimens was 99 % . Blood smears for parasites on day 28 showed one positive in the AD + mefloquine group and 7 positive in the AD group . We conclude that provision of blister packs of daily doses is a very effective way to improve compliance with short courses and drug combinations , but the efficacy of the combination in Myanmar in this particular study was only marginally higher than that of AD alone OBJECTIVE WHO recommends artemisinin suppository formulations as pre-referral treatment for children who are unable to take oral medication and can not rapidly reach a facility for parenteral treatment . We investigated factors influencing caretakers ' adherence to referral advice following pre-referral treatment of their children with rectal artesunate suppositories . METHODS The study was nested within an intervention study that involved pre-referral treatment of all children who came to a community dispenser for treatment because they were unable to take oral medications because of repeated vomiting , lethargy , convulsions or altered consciousness . All patients who did not comply with referral advice were stratified by actions taken post-referral : taking their children to a drug shop , a traditional healer , or not seeking further treatment , and added to a r and om selection of patients who complied with referral advice . Caretakers of the children were interviewed about their socio-economic status ( SES ) , knowledge about malaria , referral advice given and actions they took following pre-referral treatment . Interview data for 587 caretakers were matched with symptoms of the children , the time of treatment , arrival at a health facility or other actions taken post-pre-referral treatment . RESULTS The majority ( 93.5 % ) of caretakers reported being given referral advice by the community drug dispenser . The odds of adherence with this advice were three times greater for children with altered consciousness and /or convulsions than for children with other symptoms [ odds ratio ( OR ) 3.47 , 95 % confidence interval ( CI ) 2.32 - 5.17 , P < 0.001 ] . When question ed , caretakers who remembered when ( OR 2.19 , 95 % CI 1.48 - 3.23 , P < 0.001 ) and why ( OR 1.77 , 95 % CI 1.07 - 2.95 , P = 0.026 ) they were advised to proceed to health facility - were more likely to follow referral advice . Cost did not influence adherence except within a catchment area of facilities that charged for services . In these areas , costs deterred adherence by four to five times for those who had previously paid for laboratory services ( OR = 0.25 , 95 % CI : 0.09 - 0.67 , P = 0.006 ) or consultation ( OR 0.20 , 95 % CI : 0.06 - 0.61 , P = 0.005 ) compared with those who had not . CONCLUSION When given referral advice , caretakers of patients with life-threatening symptoms adhere to referral advice more readily than other caretakers . Health service charges deter adherence Artemisinin-based combination therapy ( ACT ) is one strategy recommended to increase cure rates in malaria and to contain resistance to Plasmodium falciparum . In the Maheba refugee settlement , children aged 5 years or younger with a confirmed diagnosis of uncomplicated falciparum malaria are treated with the combination of sulphadoxine-pyrimethamine ( 1 day ) and artesunate ( 3 days ) . To measure treatment adherence , home visits were carried out the day after the last treatment dose . Patients who had any treatment dose left were considered certainly non-adherent . Other patients ' classification was based on the answers to the question naire : patients whose caretakers stated the child had received the treatment regimen exactly as prescribed were considered probably adherent ; all other patients were considered probably non-adherent . Reasons for non-adherence were assessed . We found 21.2 % ( 95 % CI [ 15.0 - 28.4 ] ) of the patients to be certainly non-adherent , 39.4 % ( 95 % CI [ 31.6 - 47.6 ] ) probably non-adherent , and 39.4 % ( 95 % CI [ 31.6 - 47.6 ] ) probably adherent . Insufficient explanation by the dispenser was identified as an important reason for non-adherence . When considering the use of ACT , the issue of patient adherence remains challenging . However , it should not be used as an argument against the introduction of ACT . For these treatment regimens to remain efficacious on a long-term basis , specific and locally adapted strategies need to be implemented to ensure completion of the treatment A study on efficacy and effectiveness of artemisinin ( total dose of 60 mg/kg ) and artesunate ( total dose of 12 mg/kg over five days ) in treatment of uncomplicated malaria was conducted in highly malaria transmitted areas in Vietnam . 126 uncomplicated malaria cases finished 14 day follow-up . 100 % cure rate achieved at day 14 in patients of the efficacy groups received either artemisinin or artesunate , while it was 83 % and 93 % in patients treated respectively with artemisinin and artesunate of the effectiveness groups . Compliance of the treatment regimens was discussed BACKGROUND The six-dose regimen of artemether-lumefantrine is effective and is among combination therapies prioritised to replace antimalarials that no longer work in Africa . However , its effectiveness has not been assessed in the field , and could be compromised by poor adherence , incorrect timing of doses , and insufficient intake of fatty foods with every dose . Our aim , therefore , was to assess the effectiveness of artemether-lumefantrine prescribed under routine outpatient conditions , compared with its efficacy when given under supervision to in patients with acute uncomplicated falciparum malaria . METHODS We did a r and omised trial to compare the efficacy , safety , and pharmacokinetics of artemether-lumefantrine when given in a supervised ( all doses observed with fatty-food intake ; n=313 ) or unsupervised ( first dose supervised followed by outpatient treatment with nutritional advice ; n=644 ) setting to patients of all ages ( weight > 10 kg ) with acute , uncomplicated falciparum malaria in Mbarara , Ug and a. Our primary endpoint was 28 day , PCR-adjusted , parasitological cure rate . Analysis was by intention to treat and evaluability analysis . FINDINGS 38 patients were lost to follow-up and one withdrew consent . Day-28 cure rates were 97.7 % ( 296 of 303 ) and 98.0 % ( 603 of 615 ) in the supervised and unsupervised groups , respectively . We recorded 15 non-severe , drug-related adverse events , all of which resolved . INTERPRETATION Artemether-lumefantrine has a high cure rate irrespective of whether given under supervision with food or under conditions of routine clinic practice . If used as first-line treatment , artemether-lumefantrine could make a substantial contribution to malaria control in Africa , though cost is an issue AIMS Multi-drug resistant Plasmodium falciparum malaria is a rapidly increasing problem in the world , particularly Thail and . Practical antimalarial regimens which are highly effective against multi-drug resistant parasites with short-term course of administration are needed . In this study , we assessed the patient compliance of a short course regimen using artemether-mefloquine . METHODS Clinical effectiveness ( efficacy , tolerability and patient compliance ) of a 2-day regimen of artemether-mefloquine was evaluated in 126 patients with acute uncomplicated falciparum malaria who were attending the two malaria clinics in an area of highly multi-drug resistant P. falciparum malaria ( Thai-Myanmar border ) . Patients were treated with a single oral dose of 300 mg artemether on the day of attendance . Two additional doses of mefloquine were given for home treatment on the following day ( 750 and 500 mg after breakfast and lunch , respectively ) . RESULTS The combination regimen was effective , with a cure rate of 92.6 % . Based upon the concentrations of whole blood mefloquine on day-2 , compliance for this 2 day regimen of artemether-mefloquine was 98.1 % ( full compliance 86.8 % , partial compliance 11.3 % , non-compliance 1.9 % ) . CONCLUSIONS We conclude that the 2 day regimen of artemether-mefloquine is , at present , a good alternative regimen for the treatment of uncomplicated multi-drug resistant falciparum malaria |
2,227 | 19,939,787 | On the basis of post hoc subgroup analyses , coping skills training for smoking relapse prevention is effective for motivated community quitters . | BACKGROUND Existing systematic review s have concluded that psycho-educational interventions for smoking relapse prevention were ineffective .
Our objective was to conduct an exploratory meta- analysis , guided by mechanisms of these complex interventions for preventing smoking relapse . | Subjects ( N = 139 ) were assigned to intensive behavioral or to low-contact smoking treatment and to 2-mg nicotine gum or to placebo gum in a 2 X 2 factorial design . The 2-mg gum produced higher abstinence rates than did the placebo . Subjects receiving the low-contact condition plus the 2-mg nicotine gum had excellent abstinence rates at both 26 weeks ( 56 % abstainers ) and 52 weeks ( 50 % abstainers ) . Smokers who scored at the median on a measure of physical dependence to nicotine were more likely to benefit by nicotine gum treatment than subjects who scored either higher or lower , but this relation was nonsignificant . The results of this study are compared with an earlier nonblind trial The authors present results of a r and omized clinical trial of the efficacy of extended treatment with bupropion SR in producing longer term cigarette smoking cessation . Adult smokers ( N = 362 ) received open-label treatment ( 11 weeks ) that combined relapse prevention training , bupropion SR , and nicotine patch followed by extended treatment ( 14 weeks ) with bupropion SR or matching placebo . Abstinence percentages were relatively high ( week 11 : 52 % ; week 25 : bupropion , 42 % ; placebo , 38 % ; week 52 : bupropion , 33 % ; placebo , 34 % ) , but bupropion SR did not surpass placebo . Gender and baseline craving level were identified as significant , independent moderators of treatment response . Men were more likely to abstain than women ( week 11 : 59 % vs. 43 % , p = .001 ; week 25 : 48 % vs. 31 % , p = .001 ; week 52 : 39 % vs. 27 % , p = .01 ) . Because most smokers suffer relapse with any current cessation treatment , the comparatively high abstinence percentages achieved in this trial are of interest AIMS In an additive design , test the efficacy of cue exposure treatment for smoking relapse prevention as an adjunct to current st and ard cognitive behavioral and pharmacological treatments . DESIGN R and omized , controlled clinical trial . SETTING Outpatient behavioral medicine clinic . PARTICIPANTS One hundred and twenty-nine cigarette smokers recruited through newspaper advertisements . INTERVENTION After receiving an initial counseling session for cessation and setting a quit day , 129 smokers were r and omly assigned to one of four relapse prevention treatment conditions : ( 1 ) brief cognitive behavioral ; ( 2 ) cognitive behavioral and nicorette gum ; ( 3 ) cognitive behavioral and cue exposure ; and ( 4 ) cognitive behavioral and cue exposure with nicorette gum . All smokers met individually with their counselor for six RP sessions . MEASURES Seven-day , point-prevalence abstinence rates ( CO verified ) taken at 1 , 3 , 6 and 12-months post-treatment and time to first slip . FINDINGS All manipulation checks and process measures suggested that the treatments were delivered as intended . There were no significant differences between conditions in point-prevalence abstinence rates or in time to first slip . CONCLUSIONS These results call into question the utility of cue exposure treatment for smoking relapse prevention Internet interventions for smoking cessation are ubiquitous . Yet , to date , there are few r and omized clinical trials that gauge their efficacy . This study is a r and omized clinical trial ( N= 284 , n= 140 in the treatment group , n= 144 in the control group ) of an Internet smoking cessation intervention . Smokers were r and omly assigned to receive either bupropion plus counseling alone , or bupropion and counseling in addition to 12 weeks of access to the Comprehensive Health Enhancement Support System for Smoking Cessation and Relapse Prevention ( CHESS SCRP ; a Web site which provided information on smoking cessation as well as support ) . We found that access to CHESS SCRP was not significantly related to abstinence at the end of the treatment period ( OR= 1.13 , 95 % CI 0.66 - 2.62 ) or at 6 months postquit ( OR= 1.48 , 95 % CI 0.66 - 2.62 ) . However , the number of times participants used CHESS SCRP per week was related to abstinence at both end of treatment ( OR= 1.79 , 95 % CI 1.25 - 2.56 ) and at the 6-month follow-up ( OR= 1.59 , 95 % CI 1.06 - 2.38 ) . Participants with access to CHESS SCRP logged in an average of 33.64 times ( SD=30.76 ) over the 90-day period of access . Rates of CHESS SCRP use did not differ by ethnicity , level of education or gender ( all p>.05 ) . In sum , results suggest that participants used CHESS SCRP frequently , CHESS SCRP use was related to success , but the effects in general did not yield intergroup effects 1,218 smokers able to quit smoking for 48 hr were r and omly assigned to one of 12 cells in a 4 x 3 fully crossed factorial experiment . A pharmacologic factor contained four levels : nicotine polacrilex ( gum ) delivered ad lib or on a fixed regimen , placebo gum , and no gum . A self-guided behavioral treatment factor contained three levels : self-selected relapse prevention modules , r and omly administered modules , and no modules . Those receiving nicotine gum were more likely to be abstinent at the 2- and 6-month follow-ups . The fixed regimen accounted for most of the effect for gum . There was no effect for the relapse prevention module factor . Men and women showed a differential treatment response . Men who received nicotine gum were more likely to be abstinent at each follow-up ( 2 , 6 , and 12 months ) . No treatment was significantly better among women . We conclude that research on different gum chewing regimens is warranted and that further examination of possible gender differences in response to replacement therapy is needed BACKGROUND Pediatric well-care visits provide a clinical opportunity to counsel new mothers about their smoking and the deleterious effects of environmental tobacco smoke ( ETS ) on infant health . METHODS Forty-nine Oregon pediatric offices enrolled 2,901 women who were currently smoking or had quit for pregnancy , using a brief survey at the newborn 's first office visit . R and omly assigned offices provided advice and material s to mothers at each well-care visit during the first 6 months postpartum to promote quitting or relapse prevention . RESULTS The intervention reduced smoking ( 5.9 % vs 2.7 % ) and relapse ( 55 % vs 45 % ) at 6-month follow-up , but logistic regression analysis at 12 months revealed no significant treatment effect . The intervention had a positive effect on secondary outcome variables , such as readiness to quit and attitude toward and knowledge of ETS . Multiple logistic regression analysis indicated that husb and /partner smoking was the strongest predictor of maternal quitting or relapse . CONCLUSIONS A pediatric office-based intervention can significantly affect smoking and relapse prevention for mothers of newborns , but the effect decreases with time . Consistent prompting of the provider to give brief advice and material s at well-care visits could provide a low-cost intervention to reduce infant ETS exposure OBJECTIVE To evaluate the effectiveness of individually tailored smoking cessation advice letters as an adjunct to telephone counselling and generic self-help material s. DESIGN R and omized controlled trial . SETTING The UK Quitline . PARTICIPANTS A total of 1508 current smokers and recent ex-smokers . INTERVENTIONS The control group received usual care ( telephone counselling and an information pack sent through the post ) . The intervention group received in addition a computer-generated individually tailored advice letter . MAIN OUTCOME MEASURES All outcomes were assessed at 6-month follow-up . The primary outcome measure was self-reported prolonged abstinence for at least 3 months . Secondary outcomes were self-reported prolonged abstinence for at least 1 month and 7-day and 24-hour point-prevalence abstinence . RESULTS For the sample as a whole , quit rates did not differ significantly between the two conditions . However , among the majority ( n = 1164 ) who were smokers at baseline , quit rates were consistently higher in the intervention group : prolonged abstinence for 3 months , 12.2 % versus 9.0 % [ odds ratio ( OR ) = 1.40 , 95 % confidence interval ( CI ) = 0.96 - 2.04 , P = 0.080 ) ; prolonged abstinence for 1 month , 16.4 % versus 11.3 % ( OR = 1.53 , 95 % CI = 1.09 - 2.15 , P = 0.013 ) ; 7-day point-prevalence abstinence , 18.9 % versus 12.7 % ( OR = 1.59 , 95 % CI = 1.15 - 2.19 , P = 0.004 ) ; 24-hour point-prevalence abstinence , 20.9 % versus 15.4 % ( OR = 1.45 , 95 % CI = 1.07 - 1.96 , P = 0.015 ) . CONCLUSIONS The results for the smokers are encouraging in showing a small but useful effect of the tailored letter on quit rate . Versions of the tailoring program could be used on the web and in general practice s , pharmacies and primary care trusts AIMS To evaluate relapse prevention ( relapse prevention ) and contingency management ( contingency management ) for optimizing smoking cessation outcomes using nicotine replacement therapy for methadone-maintained tobacco smokers . DESIGN Experimental , 2 ( relapse prevention)x2 ( contingency management ) repeated measures design using a platform of nicotine replacement therapy featuring a 2-week baseline period , followed by r and omization to 12 weeks of treatment , and 6- and 12-month follow-up visits . SETTING Three narcotic treatment centers in Los Angeles . PARTICIPANTS One hundred and seventy-five participants who met all inclusion and no exclusion criteria . INTERVENTION Participants received 12 weeks of nicotine replacement therapy and assignment to one of four conditions : patch-only , relapse prevention + patch , contingency management + patch and relapse prevention + contingency management + patch . MEASUREMENTS Thrice weekly sample s of breath ( analyzed for carbon monoxide ) and urine ( analyzed for metabolites of opiates and cocaine ) and weekly self-reported numbers of cigarettes smoked . FINDINGS Participants ( 73.1 % ) completed 12 weeks of treatment . During treatment , those assigned to receive contingency management showed statistically higher rates of smoking abstinence than those not assigned to receive contingencies ( F3,4680=6.3 , P=0.0003 ) , with no similar effect observed for relapse prevention . At follow-up evaluations , there were no significant differences between conditions . Participants provided more opiate and cocaine-free urines during weeks when they met criteria for smoking abstinence than during weeks when they did not meet these criteria ( F1,2054=14.38 , P=0.0002 ; F1,2419=16.52 , P<0.0001 ) . CONCLUSIONS Contingency management optimized outcomes using nicotine replacement therapy for reducing cigarette smoking during treatment for opiate dependence , although long-term effects are not generally maintained . Findings document strong associations between reductions in cigarette smoking and reductions in illicit substance use during treatment Effects of smoking-cessation treatment combining transdermal nicotine substitution with behavioral therapy were investigated in two studies . A total of 403 smokers underwent nine weeks of behavioral self-control treatment . For seven weeks , groups with transdermal nicotine substitution were also provided with nicotine patches that continuously release nicotine through the skin into the circulatory system . The effects of treatment were measured by total abstinence . The results showed that the nicotine concentration in the patch , special relapse prevention methods , and the type of dosage ( individual versus fixed dose ) had no influence on therapeutic success . Nicotine concentration played a decisive role in the compatibility of the patch . Combining transdermal nicotine substitution with behavioral therapy produced 12-month success rates ( total abstinence ) of about 35 % Abstract Objective : To evaluate a smoking cessation intervention that can be routinely delivered to smokers admitted with cardiac problems . Design : R and omised controlled trial of usual care compared with intervention delivered on hospital wards by cardiac rehabilitation nurses . Setting : Inpatient wards in 17 hospitals in Engl and . Participants : 540 smokers admitted to hospital after myocardial infa rct ion or for cardiac bypass surgery who expressed interest in stopping smoking . Intervention : Brief verbal advice and st and ard booklet ( usual care ) . Intervention lasting 20 - 30 minutes including carbon monoxide reading , special booklet , quiz , contact with other people giving up , declaration of commitment to give up , sticker in patient 's notes ( intervention group ) . Main outcome measures : Continuous abstinence at six weeks and 12 months determined by self report and by biochemical validation at these end points . Feasibility of the intervention and delivery of its components . Results : After six weeks 151 ( 59 % ) and 159 ( 60 % ) patients remained abstinent in the control and intervention group , respectively ( P=0.84 ) . After 12 months the figures were 102 ( 41 % ) and 94 ( 37 % ) ( P=0.40 ) . Recruitment was slow , and delivery of the intervention was inconsistent , raising concerns about the feasibility of the intervention within routine care . Patients who received the declaration of commitment component were almost twice as likely to remain abstinent than those who did not receive it ( P<0.01 ) . Low dependence on tobacco and high motivation to give up were the main independent predictors of positive outcome . Patients who had had bypass surgery were over twice as likely to return to smoking as patients who had had a myocardial infa rct ion . Conclusions : Single session interventions delivered within routine care may have insufficient power to influence highly dependent smokers . What is already known on this topic Stopping smoking after a serious cardiac event is associated with a significant decrease in mortality Up to 70 % of smokers who survive cardiac surgery smoke again within a year Intensive interventions delivered by dedicated staff can help cardiac patients not to start to smoke again What this study adds An intervention delivered by cardiac rehabilitation nurses within routine care during patients ' hospital stay failed to increase the number who managed to stop smoking in the long term For busy staff with competing priorities , the 30 minute intervention was also on the borderline of practicability Patients admitted after a myocardial infa rct ion were over twice as likely to give up than those admitted for a bypass BACKGROUND A partner 's provision of support and smoking status has been consistently associated with women 's likelihood of smoking cessation during pregnancy and relapse in postpartum . DESIGN A three-group r and omized controlled intervention trial was conducted in 1996 to 2001 , with 583 women and their partners r and omized to usual care ( UC ) , woman-only ( WO ) , or partner-assisted ( PA ) intervention . Follow-ups occurred at 28 weeks of pregnancy , and 2- , 6- , and 12-months postpartum . SETTING Womack Army Medical Center ( WAMC ) at Fort Bragg in Fayetteville , North Carolina . INTERVENTION Women in the UC condition received provider advice to quit and a self-help guide . The WO condition received UC components plus a late-pregnancy relapse prevention kit ( booklet and gift items ) and six counseling calls ( three in pregnancy and three postpartum ) initiated by a health advisor . Women in the PA condition received the WO intervention , and their partners received telephone counseling and a support guide emphasizing skills to help the woman build and maintain her confidence to quit smoking . Partners who smoked also received cessation aids and related counseling . MAIN OUTCOME MEASURE Seven-day self-reported abstinence from smoking at each follow-up . RESULTS Intent-to-treat analyses showed no significant differences by condition in women 's reports of abstinence at any follow-up . In late pregnancy , more partners were abstinent in the PA condition ( 15 % ) than in the UC condition ( 5 % ) , p = 0.02 . CONCLUSIONS Partner-assisted smoking-cessation interventions need further refinement . Influencing young couples ' support patterns may require more intensive and conjoint intervention . Partners who smoke could benefit from support for their cessation efforts Our objective was to examine the efficacy of the added effect of individualized smoking relapse prevention counseling on obstetricians ' and nurse midwives ' usual advice during prenatal care . One hundred and seventy-five pregnant women who were smoking early in their pregnancy , but had quit by first prenatal visit , were r and omly assigned to receive the usual advice from their obstetrician or nurse midwife , or usual advice plus individual relapse prevention counseling . Smoking status was measured by self-report , by urinary cotinine/creatinine ratio at the 36-week visit , and by self-report at long-term postpartum follow-up . We found that a smaller percentage of women in the intervention group ( 8.8 % ) reported smoking at the thirty-sixth-week visit than those in the usual care group ( 16.9 % ) , a nonsignificant difference . No significant difference in relapse rates during pregnancy was observed based on urinary cotinine/creatinine ratios , but these rates , 29.5 % and 27.9 % respectively , were substantially higher than those based on self-report . The average number of days abstinent reported by women in the intervention group was significantly longer than that in the usual care group , 199 days versus 166 days respectively ( P < .01 ) . Logistic regression analysis indicated that longest time abstaining before first visit , level of belief in smoking 's harm to the fetus , and motivation to smoke were independently related to the probability of relapsing to smoking by the 36-week visit . Long-term relapse rates were not significantly different : intervention group , 50.9 % , usual care group , 50.0 % . ( ABSTRACT TRUNCATED AT 250 WORDS A multicomponent smoking relapse prevention treatment based on Marlatt and Gordon 's ( 1980 ) model of the relapse process was developed and evaluated . Behavior-analytic methods were used to develop assessment instruments , training situations , and coping responses . The prevention components were presented in the context of a basic broad-spectrum stop-smoking program , and were compared with the basic program plus discussion control , and the basic program alone . Smoking-related dependent variables generally did not differ between groups at any time from pre-treatment to 12 month follow-up . Only the subjects in the relapse prevention condition improved problem-solving and social skills needed to cope with high-risk situations . These subjects also tended to take longer to relapse and smoke fewer cigarettes at the time of relapse . Subjects above the median level of competence on measures of social skill at post-treatment remained abstinent significantly longer . Maintenance of non-smoking was found to be related to the degree of competence with which individuals deal with high-risk situations . Results are discussed in relation to models of compliance with therapeutic regimens AIM To investigate the efficacy of maintenance treatment with bupropion and /or nicotine gum for reducing smoking relapse . DESIGN , SETTING AND PARTICIPANTS A 48-week study was conducted at a university-based smoking cessation clinic between February 2001 and October 2005 . A total of 588 smokers received bupropion and nicotine patch in 8 weeks of open-label treatment ( OLT ) ; 289 abstainers during the last 4 weeks of OLT were r and omized in double-blind placebo-controlled fashion to one of four arms for 16 weeks of maintenance treatment ( MT ) followed by 24 weeks of non-treatment follow-up ( NTFU ) . INTERVENTION Bupropion ( 300 mg/day ) and 2 mg nicotine gum , used alone or combined , and comparable placebo pill and placebo gum . Behavioral counseling at all visits . OUTCOME Time to relapse ( TTR ) from r and omization . Relapse is defined as the first 7 consecutive days of smoking . Abstinence verified by carbon monoxide < or= 8 parts per million . FINDINGS TTR was longer with extended active treatments compared to placebo ( median days to relapse : bupropion + placebo = 136 , nicotine + placebo = 98 , bupropion + nicotine = 90 , double placebo = 71 ) . Hazard ratios ( HR ) for relapse were statistically significant for bupropion + placebo versus double placebo during MT ( HR = 0.59 , 95 % CI = 0.37 - 0.92 ) and to the end of NTFU ( HR = 0.66 , 95 % CI = 0.42 - 0.96 ) . However , bupropion 's advantage dissipated upon stopping the drug . Gum use was low , preventing a valid assessment ; but analysis restricted to gum users suggested a weak effect of extended nicotine gum . CONCLUSION Maintenance treatment with bupropion exerted a modest benefit for preventing smoking relapse ; the optimum duration of bupropion treatment was unclear . Further research is needed to ascertain the merits of extended use of nicotine gum , other nicotine replacement agents and other treatments known to aid smokers for preventing relapse once abstinence is achieved Smokers aged 18 to 65 years ( N = 1,044 ) who were able to quit for 24 hr were r and omized using a 2 x 2 factorial design to compare nicotine gum to no gum use and self-help material s to no use of material s. All participants were offered a $ 100 incentive to quit and stay quit for 6 months . Six-month abstinence was 27 % in the gum groups , compared with 19 % in the no-gum group ( p = .002 ) . Compared with the no-gum group , relapse occurred at a significantly lower rate in the gum group for the entire 12 months of follow-up ( odds of relapse in the gum group was 0.72 , 95 % confidence interval , 0.62 to 0.83 ) . There was no significant main effect for the self-help material s , no interaction between gum and material s , and no evidence that the effectiveness of gum differed between the sexes or between heavy and light smokers . Nicotine gum is an effective adjunct to minimal-contact smoking cessation material s plus monetary incentive in a population -based sample of smokers AIMS Tobacco dependence treatments achieve abstinence rates of 25 - 30 % at 1 year . Low rates may reflect failure to conceptualize tobacco dependence as a chronic disorder . The aims of the present study were to determine the efficacy of extended cognitive behavioral and pharmacological interventions in smokers > or = 50 years of age , and to determine if gender differences in efficacy existed . DESIGN Open r and omized clinical trial . SETTING A free-st and ing , smoking treatment research clinic . PARTICIPANTS A total of 402 smokers of > or = 10 cigarettes per day , all 50 years of age or older . INTERVENTION Participants completed a 12-week treatment that included group counseling , nicotine replacement therapy ( NRT ) and bupropion . Participants , independent of smoking status , were then assigned r and omly to follow-up conditions : ( i ) st and ard treatment ( ST ; no further treatment ) ; ( ii ) extended NRT ( E-NRT ; 40 weeks of nicotine gum availability ) ; ( iii ) extended cognitive behavioral therapy ( E-CBT ; 11 cognitive behavioral sessions over a 40-week period ) ; or ( iv ) E-CBT plus E-NRT ( E-combined ; 11 cognitive behavioral sessions plus 40 weeks nicotine gum availability ) . MEASUREMENTS Primary outcome variable was 7-day point prevalence cigarette abstinence verified biochemically at weeks 24 , 52 , 64 and 104 . FINDINGS The most clinical ly important findings were significant main effects for treatment condition , time and the treatment x time interaction . The E-CBT condition produced high cigarette abstinence rates that were maintained throughout the 2-year study period [ ( week 24 ( 58 % ) , 52 ( 55 % ) , 64 ( 55 % ) and 104 ( 55 % ) ] , and was significantly more effective than E-NRT and ST across that period . No other treatment condition was significantly different to ST . No effects for gender were found . CONCLUSIONS Extended cognitive behavioral treatments can produce high and stable cigarette abstinence rates for both men and women . NRT does not add to the efficacy of extended CBT , and may hamper its efficacy . Research is needed to determine if these results can be replicated in a sample with a greater range of ages , and improved upon with the addition of medications other than NRT Many effective behavioral and pharmacologic therapies are now available for treatment of smoking . The most effective strategy for treatment is combined behavioral intervention and pharmacologic therapy ( 1 ) . Effective pharmacologic interventions for smoking cessation include several types of nicotine replacement and use of the non-nicotine medication bupropion ( 2 , 3 ) . Despite treatment advances , smoking relapse after successful intervention for smoking cessation occurs in 70 % to 80 % of patients within 6 to 12 months ( 4 ) . Studies of relapse prevention strategies suggest that teaching coping skills may reduce the risk for relapse , but other behavioral therapies have shown little benefit ( 5 , 6 ) . Because pharmacologic therapy for smoking cessation has been proven effective and behavioral relapse prevention strategies alone have shown no great benefit , pharmacologic therapy for relapse prevention should be evaluated . Bupropion has been proven an effective intervention for smoking cessation , both as a single therapy and in combination with nicotine-patch therapy ( 2 , 3 ) . Because bupropion is effective for initiating abstinence from smoking and is safe for long-term therapy , we hypothesized that prolonged bupropion treatment in recently abstinent smokers would decrease the relapse rate . We compared sustained-release bupropion treatment with placebo for 1 year in participants who achieved initial abstinence after 7 weeks of therapy with open-label , sustained-release bupropion . Methods Participants This r and omized , double-blind , placebo-controlled study of relapse prevention was performed at five sites ( Mayo Clinic , Rochester , Minnesota ; the Palo Alto Center for Pulmonary Disease Prevention , Palo Alto , California ; Brown University , Providence , Rhode Isl and ; Oregon Health Sciences University , Portl and , Oregon ; and Massachusetts General Hospital , Boston , Massachusetts ) and was approved by the institutional review board at each site . We recruited participants through advertisements and press releases . After passing an initial screening interview by telephone , participants attended an informational meeting . At this meeting , the study was explained and the participants completed question naires and gave written , informed consent . The volunteers were eligible for study inclusion if they were 18 years of age or older , had smoked an average of at least 15 cigarettes or more per day for the past year , were motivated to stop smoking , and were in generally good health . Only one smoker per household was allowed in the study . Exclusion criteria included a personal or family history of a seizure disorder ; history of severe head trauma ; predisposition to seizures ( such as history of brain tumor or stroke ) ; history or current diagnosis of anorexia nervosa or bulimia ; presence of an unstable medical or psychiatric condition ; pregnancy ; lactation ; dependence on alcohol or other nonnicotine substance in the past year ; current use of psychotropic medications ; previous use of bupropion ; current use of tobacco products other than cigarettes ; or current use of any therapy for smoking cessation [ such as nicotine replacement therapy ; fluoxetine , clonidine , buspirone , or doxepin therapy ; or behavioral therapy ] . Persons with current major depression were also excluded . Potential participants were deemed to have current major depression if : 1 ) they met the criteria for this condition on the basis of their responses in a structured clinical interview [ conducted by a trained study assistant ] , or 2 ) they were judged to have major depression by the physician performing the entrance history and physical examination ( 7 ) . Treatment Beginning at the baseline visit and continuing through study week 7 , all participants received open-label , sustained-release bupropion ( bupropion SR ) , 300 mg/d ( 150 mg/d for 3 days , followed by 150 mg twice daily ) . At the baseline visit , participants were instructed to set a target quitting date after 1 week of medication use [ usually day 8 of therapy ] . Each participant attended weekly follow-up visits during the 7-week open-label phase . Participants were eligible for r and om assignment to receive bupropion or placebo in the double-blind phase if they 1 ) reported not smoking [ not even a puff ] during week 7 of the open-label phase and 2 ) had their self-report confirmed by an expired carbon monoxide level of 10 parts per million ( ppm ) or less . The r and omly assigned participants returned for 14 visits during the double-blind phase ( at weeks 8 , 9 , 10 , 12 , 16 , 20 , 24 , 28 , 32 , 36 , 40 , 44 , 48 , and 52 ) and 5 visits during the follow-up year ( at weeks 53 , 56 , 64 , 78 , and 104 ) . Participants also received a telephone follow-up at 21 months after study enrollment . At the baseline physical examination , each participant received a brief personalized message from the examining physician to stop smoking , set a target quitting date , and received self-help material that was based on a smoking cessation program design ed by the U.S. National Cancer Institute ( 8) . At each visit during the open-label and double-blind study phases , study assistants counseled participants for approximately 10 to 15 minutes . R and omization to the placebo or bupropion groups was computer generated at a central location ; the investigators did not know the patient assignments . All bupropion and placebo pills were identical in shape , size , and color . Assessment s At baseline , participants had a physical examination ; underwent chest radiography , laboratory testing , and electrocardiography ; and completed a Fagerstrm Tolerance Question naire and a Beck Depression Inventory . The Fagerstrm Tolerance Question naire is a widely used measure of nicotine dependence with scores that range from 0 to 11 ; scores of 6 or greater indicate higher levels of dependence ( 9 , 10 ) . At each visit through week 53 , study assistants recorded adverse experiences , as well as use of study and concomitant medications . Participants maintained a daily diary of withdrawal symptoms ( 11 ) and daily cigarette use that was review ed at each visit through week 12 . The Beck Depression Inventory ( administered at baseline and weeks 7 , 8 , 12 , 52 , 53 , 56 , 78 , and 104 ) is a 21-item , self-administered question naire that assesses severity of depressive symptoms ( 12 ) . Smoking status was self-reported at each visit ; reports of abstinence were considered vali date d with a measurement of carbon monoxide level in expired air of no higher than 10 ppm . Outcome Measures The main outcomes of interest were 1 ) weekly point-prevalence abstinence during medication treatment , 2 ) continuous abstinence during medication treatment , and 3 ) time to first relapse . Secondary outcomes included weight change over time and point prevalence and continuous-abstinence rates after completion of drug therapy . The weekly point-prevalence smoking status was defined as 1 ) self-report of not smoking during the previous 7 days that was confirmed by an expired air carbon monoxide level of 10 ppm or lower and 2 ) two or fewer consecutive missed visits . Smoking relapse was defined as a self report of smoking or an expired air carbon monoxide level greater than 10 ppm . Participants were also considered to have smoking relapse if they missed more than two consecutive visits . All participants meeting the abstinence criteria at every visit were considered continuously abstinent . Self-report determined the date of smoking relapse . For participants who self-reported not smoking but who were classified as smoking because of an elevated carbon monoxide level or because of consecutive missed visits , the date of relapse was defined as the day after the most recent previous study visit at which smoking abstinence was biochemically confirmed . Statistical Analysis We determined that we needed a sample size of 170 participants in each r and omly assigned treatment group to detect a significant between-group difference in end-of-treatment abstinence rates of 0.15 at a significance level of 0.05 and a power of 0.80 . Assuming an abstinence rate of 35 % for week 7 of the open-label phase , we determined that up to 1000 enrollees were needed to ensure a minimum sample of 340 nonsmoking participants ( 170 per group ) for r and omization . The 1-week point prevalence for smoking status during week 7 of the open-label bupropion phase was used to determine eligibility for r and om assignment to receive placebo or active sustained-release bupropion , 300 mg/d . To compare the baseline characteristics of the bupropion and placebo recipients , we used the two- sample t-test and the chi-square test for analysis of continuous and categorical variables , respectively . The efficacy of bupropion for preventing smoking relapse during the double-blind medication phase and follow-up phase was assessed by analyzing time to first smoking relapse . We used KaplanMeier survival estimates and a proportional hazards regression model ( 13 , 14 ) to analyze time to first smoking relapse . For this analysis , time to first relapse was defined as the date of first relapse minus the date of r and omization . For participants without relapse , time to first relapse was censored by using the date of their final ( week 104 ) study visit . For the proportional hazards regression analysis , the response variable was time to first smoking relapse , and the independent variable was treatment . R and omization was stratified according to study site to ensure that similar numbers of participants were assigned to the treatment groups at each site . We verified that the treatment effect was not dependent on study site by performing an initial analysis that included the interaction of treatment by study site . Subsequently , we used a proportional hazards regression analysis with study site as a stratification factor to assess differences between treatment groups . Rates of point prevalence and continuous smoking abstinence were compared between treatment groups by using a logistic regression analysis with smoking status as the dependent variable and BACKGROUND Varenicline , an alpha4beta2 nicotinic receptor partial agonist , has the potential to relieve nicotine craving and withdrawal symptoms while reducing the reinforcing effects of nicotine . Phase 3 studies have evaluated the effects of varenicline on inducing smoking cessation and maintaining smoking abstinence . SUBJECTS AND METHODS Two identically design ed r and omized , double-blind , smoking cessation studies recruited smokers of 10 or more cigarettes daily who were motivated to quit . Treatment with varenicline 1 mg twice daily was compared with treatment with bupropion 150 mg twice daily or matching placebo for 12 weeks , followed by a 40-week nontreatment observation period . In a third study that investigated maintenance of abstinence , smokers were treated with 12 weeks of open-label varenicline 1 mg twice daily . Subjects who did not smoke during the last week of treatment were eligible to be r and omized to varenicline or placebo for an additional 12 weeks , followed by a 28-week nontreatment observation period . Brief smoking cessation counseling was given at clinic visits or telephone contacts scheduled regularly during the entire duration of the 3 studies . Measurement of carbon monoxide in expired breath was used to verify the subjects ' reports of nonsmoking . RESULTS In the 2 smoking cessation studies , varenicline significantly increased the 4-week continuous abstinence rate during weeks 9 to 12 relative to placebo and bupropion . The continuous abstinence rate during weeks 9 to 52 was also increased compared with placebo and with bupropion ( statistically significant in one of the studies ) . In the maintenance study , smokers who quit after an initial course of open-label varenicline had greater long-term efficacy when they received an additional 12 weeks of varenicline than when they received placebo . In all 3 studies , varenicline was safe and well tolerated , with overall treatment discontinuation rates similar to that of placebo . Nausea was the adverse event that occurred more frequently in subjects receiving varenicline but was mostly mild in intensity . CONCLUSION The results of these studies demonstrate a new order of efficacy in medical therapy for smoking cessation . Varenicline proved to be more effective than bupropion in inducing cessation . Furthermore , varenicline prevented relapse in smokers who had progressed toward cessation by quitting for at least 1 week Background —Although men hospitalized with cardiovascular disease ( CVD ) show high smoking-cessation rates , similar data for women are lacking . We tested the efficacy of smoking-cessation intervention in women hospitalized for CVD . Methods and Results —In this r and omized controlled trial conducted from 1996 to 2001 , 277 women diagnosed with CVD ( mean age 61±10 years ) were r and omly assigned within 1 of 12 San Francisco Bay Area hospitals to a usual-care group ( UG ; n=135 ) or intervention group ( IG ; n=142 ) . Baseline histories were obtained , and interviews to ascertain self-reported smoking status occurred at 6 , 12 , 24 , and 30 months after hospitalization . The UG received strong physician ’s advice , a self-help pamphlet , and a list of community re sources . The IG received strong physician ’s advice and a nurse-managed cognitive behavioral relapse-prevention intervention at bedside , with telephone contact at intervals after discharge . The groups were similar demographically and had smoked cigarettes for a median of 38 ( IG ) or 40 ( UG ) years . Time to resumption of continuous smoking was assessed by Kaplan-Meier analysis , and risk differences between groups were determined . Time smoke-free was significantly greater for the IG than the UG ( P = 0.038 ) . Point prevalence for nonsmoking at the interviews was somewhat greater for the IG than the UG ( P > 0.15 at all times ) . Conclusions —Cognitive behavioral intervention result ed in longer average times to resumption of smoking , but in these 2 groups of older women with limited social and financial re sources , long-term success rates were similar . Systematic identification of smokers and even the brief intervention afforded the UG yielded a high smoking-cessation rate over time The effectiveness of a relapse prevention program was studied in a population of 744 smokers . Subjects first attended an intensive 4-day series of 2-hr meetings in which they were trained to use more than 40 behavioral and cognitive smoking cessation techniques . At the 1-week follow-up session , those abstinent from smoking ( 79 % , carbon monoxide verified ) were r and omly assigned to one of three follow-up conditions : ( a ) a three-session skills-training program in which subjects developed and actively rehearsed individually tailored coping strategies for likely relapse situations , ( b ) a three-session discussion control condition in which subjects discussed maintenance but did not develop or rehearse coping strategies , or ( c ) a no-treatment control condition . Survival analysis indicated higher abstinence rates for the skills-training group than for the control groups throughout the following year . After 12 months , the biochemically confirmed continuous abstinence rate was higher in the skills-training group ( 41.3 % ) than in the discussion and no-treatment groups ( 34.1 % and 33.3 % , respectively ) OBJECTIVES This r and omized controlled trial assessed the efficacy of a smoking relapse prevention program featuring 3 postdischarge telephone contacts with subjects who had quit smoking on hospitalization . METHODS Patients were r and omly assigned to public health nurse-mediated behaviorally oriented in-patient counseling focused on relapse prevention ( control group , n = 49 ) , or the same inpatient counseling with postdischarge telephone contacts at 7 , 21 and 42 days after discharge ( intervention group , n = 57 ) . The main outcome measure , smoking cessation rate , was obtained from self-reports at 3 , 6 and 12 months after discharge . Smoking cessation at 12 months after discharge was confirmed by urinary nicotine concentration . RESULTS At 3 , 6 and 12 months smoking cessation rates were 83 % , 63 % and 56 % for the intervention group , and 76 % , 65 % and 51 % for control group . After adjustment for sex , age , having any complication , number of family members , smoking status on admission , strength of nicotine dependence and self confidence to quit smoking , the odds ratio of cessation among the intervention group were 1.46 ( 95 % confidence interval ( CI ) : 0.48 - 4.47 ) , 0.82 ( 95 % CI : 0.31 - 2.17 ) and 0.99 ( 95 % CI : 0.40 - 2.45 ) at 3 , 6 and 12 months after discharge , respectively . CONCLUSION This program had limited efficacy to maintain postdischarge smoking abstinence . We should re-consider the modality of smoking cessation program for relapse prevention among hospitalized patients UNLABELLED PRIMARY AIM : Examine the effectiveness of extended cognitive behavior therapy ( CBT ) in promoting longer-term smoking abstinence . DESIGN Open-label treatment phase followed by extended treatment phase . R and omization conducted prior to entry into open-label treatment phase ; analysis based on intention-to-treat to avoid threat of selection bias . SETTING Community smoking cessation clinic . PARTICIPANTS A total of 304 adult smokers ( > or = 18 years of age ; > or = 10 cigarettes/day ) . INTERVENTION Open-label ( 8 weeks ) : all participants received bupropion SR , nicotine patch , CBT . Extended treatment ( 12 weeks ) : participants received either CBT + voicemail monitoring and telephone counseling or telephone-based general support . MEASUREMENTS Seven-day point prevalence abstinence , expired-air carbon monoxide . RESULTS At week 20 follow-up , CBT produced a higher 7-day point prevalence abstinence rate : 45 % versus 29 % , P = 0.006 ; at 52 weeks the difference in abstinence rates ( 31 % versus 27 % ) was not significant . History of depression was a moderator of treatment . Those with a positive history had a better treatment response at 20 weeks when assigned to the less intensive telephone support therapy ( P < 0.05 ) . CONCLUSION The superiority of CBT to 20 weeks suggests that continued emphasis on the development of cognitive and behavioral strategies for maintaining non-smoking during an extended treatment phase may help smokers to maintain abstinence in the longer term . At present , the minimum duration of therapy is unknown This study examined the long-term effectiveness of a postpartum smoking relapse prevention intervention by evaluating the smoking status and smoking cessation self-efficacy of original study participants at 12 months following delivery . Two hundred and thirty-eight women who had participated in a r and omized clinical trial , a nurse-delivered relapse prevention intervention , were visited in their homes . Data were collected on smoking status , self-efficacy , mental health , alcohol use , breast feeding , social support , smoking in the social environment , and sociodemographics . Smoking status was verified with measures of carbon monoxide in expired air . The 12-month continuous smoking abstinence rate was 21.0 % in the treatment group and 18.5 % in the control group ; odds ratio ( OR ) = 1.17 , 95 % confidence interval ( CI ) = 0.62 - 2.22 . One half ( 50.4 % ) of the control group and 41.2 % of the treatment group reported smoking daily at 12 months ; OR = 1.45 , 95 % CI = 0.87 - 2.43 . The treatment group attained higher self-efficacy . Four variables were associated with relapse to daily smoking ; breast feeding and mental health had protective effects , while partners who smoked and greater amount smoked prior to pregnancy had adverse effects The aim of this study was to assess the effectiveness of relapse prevention taught as a problem-solving procedure in increasing the efficacy of a behavioral program for smoking cessation at short- and longer-term , 12-mo . follow-up . 75 smokers were assigned r and omly to two treatment groups , using an additional 40 smokers who attended an information session but did not receive any treatment session as a control group . The first group ( n = 40 ) received the st and ard behavioral multicomponent program of Becoña . The program included motivational contract , self-monitoring , information on smoking , nicotine fading , stimulus control , avoidance of withdrawal symptoms , physiological feedback , and progressive self-control . The second group ( n = 36 ) , the relapse prevention group , were given the above program and an additional component of relapse prevention using a problem solving procedure . Both groups had 8 sessions of treatment . Analysis showed that at the end of treatment abstinence in the two groups was 80.0 % and 61.1 % , respectively , at the 12-mo . follow-ups 30.0 % and 36.1 % . These differences were not significant ; however , both groups were significantly different from the control group at the end of treatment ( 0 % abstinence ) and at 12-mo . follow-ups ( 2.5 % abstinence ) . These results show that the addition of this relapse prevention does not increase the number of smokers who quit or decrease the number who relapse . Further research should focus on the process of relapse and develop more effective procedures to help maintain abstinence The aim of the study was to assess the effectiveness of worksite group counselling interventions design ed to prevent smoking relapse after abstinence has been achieved following 3 months therapy using group support and /or transdermal nicotine replacement therapy . After 3 months , abstinent subjects were r and omly allocated either to a counselling group led by professional psychologists ( PG ) , to a counselling group led by former smokers ( SG ) or to no intervention group ( NG ) . The 3 and 12 months abstinence were defined , respectively , as a sustained smoking cessation during the last month , and the last 9 months . Complete abstinence was confirmed by expired carbon monoxide and by urine cotinine concentrations . The abstinence rate at 3 months was 35.1 % . After 12 months abstinence rates were not statistically different in the PG , the SG and the NG ( respectively 57.8 , 53.4 and 49.6 % of those r and omised ) . In multivariate analyzes , baseline variables associated with 12 months abstinence were non-smoking family , gender ( male ) , lower daily intake of nicotine and better psychological adjustment . Mean weight gain at 3 months in abstinent versus relapsed subjects , was respectively , 4.1 and 2.4 kg . Baseline variables associated with weight gain at 3 months were higher Fagerström score , gender ( male ) and professional status ( blue collar worker ) . Group support after abstinence has been achieved did not significantly improve the abstinence . This study shows the difficulty of preventing smoking relapse with monthly group counselling . The results indicate the need to investigate further specific programmes focusing on factors such as gender , family , nicotine dependence , psychological and weight concerns/issues which may precipitate relapse OBJECTIVES The present study used telephone support both to sustain abstinence and to encourage renewed quit attempts in smokers who had completed an intensive smoking cessation clinic . METHODS Subjects were hard-core smokers ( n = 1083 ) who had attended a multisession cessation clinic . They were then assigned r and omly to receive telephone support ( intervention calls 3 , 9 , and 21 months after the targeted cessation clinic quit date ) or no further intervention . RESULTS In the intervention condition , subjects who relapsed were significantly more likely to resume abstinence ( that is , to recycle ) than those in the comparison condition at follow-up ( 6 months : 17.8 % vs 11.3 % ; 24 months : 25.7 % vs 18.2 % ) . Telephone support was not effective in preventing relapse , and overall differences in abstinence outcome were not significant . CONCLUSIONS The major hypothesis of the current study --that telephone support would enhance the resumption of abstinence -- received partial support . However , there was no evidence either of an overall treatment effect or of an effect in preventing relapse . Telephone outreach may be more effective in the context of self-help or other less intensive interventions This study examined the postpartum relapse rates and characteristics of pregnant women who stopped smoking without professional intervention . Baseline characteristics of women who spontaneously quit were compared to women who continued to smoke . Women who spontaneously quit were also r and omized to a psychotherapy relapse prevention treatment , or to usual care . The sample was ethnically diverse , containing 141 low-income women who were predominantly Hispanic , 23 % ( n=33 ) of whom spontaneously quit smoking . The variables that significantly differentiated between " spontaneous quitters " and ongoing smokers were entered into a regression analysis , which revealed that higher self-confidence , smoking fewer cigarettes per day , and younger age accounted for 25 % of the variance in spontaneous cessation . Adding the psychotherapy intervention conferred no additional protection against relapse in this subgroup of spontaneous quitters . The six-month abstinence rate of 36 % is similar to that found in Caucasian and higher-income population s. These results extend research with pregnant smokers to a new population and may have implication s for healthcare providers and policy makers INTRODUCTION Our objective was to examine the efficacy of physicians ' advice and referral to individual counseling in preventing relapse to smoking among women who were smokers early in pregnancy , but quit prior to their first prenatal visit . DESIGN A r and omized controlled trial of prompted physician 's advice and individual relapse prevention counseling during pregnancy compared to usual physician advice . Smoking status was assessed by self-report , exhaled carbon monoxide , and urinary cotinine during pregnancy and by self-report 1 year postpartum . RESULTS There were no significant differences in relapse rates between the intervention and usual-care groups during pregnancy , nor at 1 year postpartum . Relapse rates were 23 % in both groups at the 36-week visit , and 32 % and 22 % , respectively , 1 year postpartum . Younger age , higher motivation to resume smoking , and higher levels of exhaled carbon monoxide at the first prenatal visit were predictive of relapse to smoking during pregnancy . With the conservative assumption that all those lost to follow-up relapsed , the combined 1-year postpartum relapse rate , 51 % , was 17 percentage points lower than we observed in an earlier relapse prevention trial , and 15 percentage points lower than that observed nationally a decade earlier . CONCLUSION Prompting physicians to provide supportive advice combined with referral to individual relapse prevention counseling did not reduce smoking relapse rates during pregnancy , or postpartum . However , the level of attention paid to smoking by physicians in both intervention and usual-care groups during pregnancy may have contributed to the relatively low relapse rates seen 1-year postpartum The authors compared 9- , 16- , 26- , and 52-week outcomes for two r and omly assigned groups of nicotine-dependent subjects : 1 ) nicotine patch plus four smoking cessation sessions with a nurse-practitioner giving advice and instruction ( n = 36 ; moderate-intensity condition , MI ) ; or 2 ) the foregoing treatments plus 16 weekly individual cognitive/ behavioral relapse-prevention therapy sessions ( n = 33 ; high-intensity condition , HI ) . Patch completion rates were 69.7 % in the HI group and 55.6 % in the MI group ( NS ) . Self-reported abstinence rates at the four follow-up points were comparable for the two treatment groups ; HI : 39 % , 36 % , 36 % , and 36 % ; MI : 44 % , 28 % , 25 % , and 28 % , respectively . There was some indication that MI patients with high nicotine dependence had lower abstinence rates than highly dependent HI patients OBJECTIVE To compare the combination of a nicotine inhaler and bupropion to either treatment alone for initiating smoking abstinence and relapse prevention . METHODS Smokers were r and omized to receive a nicotine inhaler , bupropion , or both for 3 months . At 3 months , smoking-abstinent study participants were r and omized to their initial medications or placebo . Participants who were smoking at 3 months were r and omized to an alternative treatment regimen or placebo . This study was conducted from July 2001 to January 2003 . RESULTS A total of 1700 smokers were r and omized to treatment ( phase 1 ) for 3 months . Among the 941 study participants eligible for r and omization to the phase 2 trial , 837 continued in the study . For the phase 2 trial , 405 smoking-abstinent participants were r and omized to relapse prevention for 9 additional months , and 432 smokers were r and omized to re-treatment for an additional 3 months . At the end of the initial 3 months of treatment ( phase 1 ) , 82 ( 14 % ) of 566 , 145 ( 26 % ) of 567 , and 194 ( 34 % ) of 567 study participants receiving a nicotine inhaler , bupropion , or both , respectively , were abstinent from smoking . Of the 405 smoking-abstinent participants at the end of 3 months , the bupropion group had more smokers than the placebo group ( mean No. of smokers , 1.5 vs 1.1 ; P < .001 ) , and the nicotine inhaler group had higher smoking abstinence rates at 12 months than the placebo group . Those receiving combination therapy had reduced rates of relapse to smoking for the first 3 months of relapse prevention , but this difference disappeared after the initial 3 months . Of the 432 study participants who were smoking at the end of 3 months and who received an alternative treatment regimen , the 223 smokers initially assigned to a nicotine inhaler were more likely to stop smoking at 6 months if they were re-treated with bupropion instead of placebo ( 8 [ 7 % ] of 111 vs 0 [ 0 % ] of 112 ; P = .003 ) , and the 209 smokers initially treated with bupropion and re-treated with a nicotine inhaler did not have significantly higher smoking abstinence rates ( 6 [ 6 % ] of 104 vs 3 [ 3 % ] of 105 ; P = -.50 ) . CONCLUSION Combined therapy with a nicotine inhaler and bupropion increased smoking abstinence rates . Continuation of the initial combination therapy does not appear to prevent relapse to smoking . Timing of re-treatment and alternative approaches to relapse prevention should be further examined Two theoretical approaches to smoking cessation were compared . Participants were r and omly assigned either to ( a ) a traditional treatment program that used contingency contracting and that emphasized the necessity for absolute abstinence ( AA ) or to ( b ) a relapse-prevention ( RP ) treatment that focused on gradual acquisition of nonsmoking skills . It was hypothesized that participants in the RP treatment would be less successful initially but would have better maintenance skills and thus would relapse less during a 1-year follow-up period . Each program was evaluated in two formats : group-based treatment and self-help material s. Results indicated comparable 1-year abstinence rates for all treatments , although more participants dropped out of the self-help formats . Participants in the RP intervention were more likely to lapse sooner after quitting and were more likely to quit again during the 1-year maintenance period . Exploratory analyses of successful participants suggested that women were more successful in the RP program and that men had greater success with the AA approach The efficacies of 2 group counseling step-up treatments for smoking cessation , cognitive-behavioral/skill training therapy ( CBT ) and motivational interviewing/supportive ( MIS ) therapy , were compared with brief intervention ( BI ) treatment in a sample of 677 smokers . Differential efficacy of the 2 step-up treatments was also tested in smokers at low and high risk for relapse ( no smoking vs. any smoking during the first postquit week . respectively ) . All participants received 8 weeks of nicotine patch therapy . BI consisted of 3 brief individual cessation counseling sessions ; CBT and MIS participants received BI treatment and 6 group counseling sessions . Neither CBT nor MIS treatment improved long-term abstinence rates relative to BI . Limited support was found for the hypothesis that high-risk smokers would benefit more from MIS than CBT . Other hypotheses were not supported OBJECTIVE To evaluate the efficacy of a brief smoking cessation intervention with pregnant women practicable routinely by midwives . DESIGN Midwives were r and omized to deliver the experimental intervention or usual care . The 10 - 15-minute intervention was based on brief counselling , written material s , arrangements for continuing self-help support and feedback on expired-air carbon monoxide levels . The intervention was tailored to the women 's needs : those who did not want to stop smoking received a brief motivational intervention , those who wanted to stop received an intervention design ed to assist them and those that had stopped recently ( recent ex-smokers ) received a relapse prevention intervention . SETTING Booking interviews with pregnant women in nine hospital and community trusts . SUBJECTS A total of 1120 pregnant women in the third month of pregnancy ( 249 recent ex-smokers and 871 current smokers ) . MAIN OUTCOME MEASURES Three indicators of biochemically vali date d abstinence were collected . Continuous abstinence for at least 3 months prior to delivery , point prevalence abstinence immediately post-delivery , and continuous abstinence from 3 months pre-delivery to 6 months post-delivery . RESULTS Only a small proportion of the women who would have been eligible to take part in the trial were actually recruited by 178 recruiting midwives , with lack of time being cited as the main barrier . The intervention and usual care groups differed in post-delivery point prevalence abstinence rates for recent ex-smokers ( 65 % vs. 53 % , p < 0.05 , one-tailed ) , but not in other outcome measures . Overall , 54 % of " recent ex-smokers " at booking and 7 % of " current smokers " at booking had been abstinent for at least 3 months at the time of delivery , and 23 % and 3 % , respectively , were still abstinent by the time the child was 6 months old ( i.e. 12 months post-intervention ) . Smoking status at follow-up was predicted by dependence indexed by time to first cigarette in the morning . CONCLUSIONS A brief " one-off " smoking cessation intervention by midwives does not seem to be a practicable or effective method of helping pregnant smokers to stop . Other options such as tailored self-help material s and telephone counselling and other specialist treatments should be examined . Current smoking cessation rates in pregnancy are very low AIM To assess the effectiveness of a new computer-generated tailored advice programme design ed to be used by smokers and recent quitters having problems staying stopped . DESIGN R and omized trial comparing a series of question naire assessment s leading to tailored computer-generated advice letters mailed at strategically relevant times , to a no extra treatment control sent st and ardized printed self-help material s. SETTING Victoria , Australia . PARTICIPANTS A total of 1058 smokers or recent quitters recruited from callers to the Quitline . MEASUREMENTS Smoking status and sustained abstinence at 12-month follow-up , plus extent of participation in the intervention . FINDINGS Using a conservative analysis ( missing data coded as a treatment failure ) , 6-month sustained abstinence was reported by significantly more participants in the computer-generated tailored advice ( 20 % ) than the st and ard printed material s condition ( 12 % ) at 12-month follow-up OR 1.82 ( 1.31 - 2.55 ) ) . Group differences in point prevalence abstinence ( 28 % intervention , 25 % control ) were not significant . Among participants in the tailored advice condition , 6-month sustained abstinence was associated with the number of advice letters received . CONCLUSION The provision of a series of tailored , computer-generated advice letters result ed in greater rates of sustained cessation than for controls . A dose-response relationship was found , with increased compliance with the intervention associated with improved cessation outcomes . The programme appears to have much of its effect by preventing relapse Relapse prevention remains a major challenge to smoking cessation efforts . T. H. Br and on , B. N. Collins , L. M. Juliano , and A. B. Lazev ( 2000 ) found that a series of 8 empirically based relapse-prevention booklets mailed to ex-smokers over 1 year significantly reduced relapse . This study dismantled 2 components of that intervention : the amount of content ( number of booklets ) and the frequency of contact . Content and contact were crossed in a 2 X 2 factorial design . The criteria of at least 1 week of abstinence at baseline was met by 431 participants , 75%-85 % of whom returned 12- , 18- , and 24-month follow-up question naires . Eight booklets produced consistently higher point-prevalence abstinence rates than did a single booklet , but frequency of contact did not affect outcome . Moreover , the high-content interventions were highly cost-effective Abstract This study evaluated the efficacy of a multiple treatment smoking cessation program and three maintenance strategies . Phase I of the study involved 51 subjects who participated in a 5-day smoking cessation project . The program consisted of lectures , demonstrations , practice exercises , aversive smoking , and the teaching of self-control procedures . In Phase II , all subjects were r and omly assigned to one of three maintenance conditions : a 4-week support group which offered an opportunity to discuss feelings and thoughts , a 4-week telephone contact system which enabled group members to call one another , and a no-contact control group . To evaluate efficacy , extensive follow-up data were collected at the end of treatment and at 2 , 4 , 6 , and 12 months post-treatment . The treatment program was extremely effective ; 100 % of the subjects were abstinent at the end of treatment , and at 1 year post-treatment , 63 % of the subjects reported total abstinence . As to sex differences , at the 1-year period 66 % of the women and 59 % of the men were ex-smokers . Recidivists reported a smoking rate that was 52 % of baseline at the 6-month follow-up . At 2 months post-treatment , 40 % of the abstainers reported that the quitting experience was easy , and subjects reported an average weight gain of only 4.69 lb . The authors offer suggestions for future smoking cessation research based upon the promising findings of this study AIM To test the efficacy of an aid to cessation/relapse prevention intervention for women postpartum . METHOD Two-armed r and omized controlled trial . Follow-ups at 6 , 12 , 18 , and 24 months , screenings on maternity wards . Intervention group received face-to-face counseling 40 days postpartum plus telephone counseling calls 4 and 12 weeks later . Control group received usual care plus self-help material for each parent . RESULTS With regard to smoking cessation , 4 week point prevalence abstinent rates were higher in the treatment group at 6 , 12 , and 18 months ( 7 % vs. 1 % , 7 % vs. 2 % , and 9 % vs. 1 % , respectively ) . Sustained abstinence was higher in the treatment group at 6 months follow-up ( 3 % vs. 0 % ) . No difference was observed with regard to relapse prevention . DISCUSSION Regarding aid to cessation we observed small effects , regarding relapse prevention no effect . In order to capitalize on the opportunity childbirth poses with regard to smoking , theories on relapse prevention in smoking cessation that guide in design ing interventions are needed Studies have demonstrated the effectiveness of smoking cessation interventions targeted at women who are smoking during pregnancy . In contrast , there is limited information about the experience of smokers who have stopped before entering prenatal care--"spontaneous quitters . " These women constitute the majority of women who stop smoking sometime during pregnancy , although evidence suggests that as many as one third relapse prior to delivery . We report the results of a population -based r and omized clinical trial that tested the effectiveness of a relapse prevention program for spontaneous quitters . The intervention consisted predominantly of printed material s received through the mail . The population ( n = 171 ) of spontaneous quitters was an ethnically diverse group of women enrolled in a large health maintenance organization . Biochemical confirmation of continuous abstinence through delivery revealed that 16 % of the women in the experimental self-help program relapsed compared with 20 % of usual care controls ( NS ) . Analysis confirmed that the program was equally ineffective among all subgroups including women at highest risk for relapse . Given the negative outcomes associated with self-help material s and clinic-based counseling reported in this and other trials , alternative intervention strategies need to be developed and tested for this significant group of prepregnancy smokers PURPOSE To determine whether ( 1 ) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting , ( 2 ) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy , and ( 3 ) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy . PARTICIPANTS AND METHODS Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates . At completion of nicotine patch therapy , nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months ( for relapse prevention ) . and smoking participants were eligible to be assigned to bupropion or placebo for 8 weeks of treatment . RESULTS Of 578 subjects , 31 % were abstinent from smoking at the end of nicotine patch therapy . Of those subjects not smoking at the end of nicotine patch therapy who entered the relapse prevention phase , 28 % and 25 % were not smoking at 6 months ( the end of the medication phase ) for bupropion and placebo , respectively ( P = .73 ) . For those still smoking at the end of nicotine patch therapy , 3.1 % and 0.0 % stopped smoking with bupropion or placebo , respectively ( P = .12 ) . CONCLUSION Tailored nicotine patch therapy for the general population of smokers can be provided in a multisite oncology investigative group setting . Bupropion did not reduce relapse to smoking in smokers who stopped smoking with nicotine patch therapy . Bupropion did not initiate abstinence among smokers who failed to stop smoking with nicotine patch therapy Lapses within the first 2 weeks of a smoking cessation attempt are strongly associated with a return to regular smoking ( S. L. Kenford et al. , 1994 ) . Unfortunately , little is known about how to prevent an initial lapse from progressing to a full relapse , and presently there are no vali date d lapse-responsive therapeutic interventions . The present study tested the efficacy and feasibility of rapid smoking plus counseling as a novel lapse-responsive intervention . Sixty-seven participants enrolled in a smoking treatment program involving brief counseling and a 9-week course of bupropion . Beginning on the quit day , participants ' smoking behavior was tracked daily for 14 days . Once an early smoking lapse was identified , participants were r and omly assigned to receive either 3 sessions of rapid smoking plus counseling or no intervention ( usual care ) . Consistent with previous research , participants who smoked during the first 2 weeks of the quit attempt had significantly poorer 6-month outcomes ( 3 % abstinent ) than did those who did not smoke ( 64 % abstinent ) . Compared with early abstainers , early lapsers were more nicotine dependent and reported greater cravings and lower confidence in their ability to abstain from smoking during the first 48 hours of abstinence . As expected , rapid smoking produced a variety of aversive effects , including increased nausea , dizziness , and vomiting as well as sharply decreased cravings to smoke . However , rapid smoking did not improve abstinence outcomes relative to usual care . Although rapid smoking has been shown to be an effective treatment for initial smoking cessation , in this preliminary study the authors failed to demonstrate its effectiveness as a lapse-responsive treatment Recent research on treatments to stop smoking has focused almost entirely on nicotine replacement , and several meta-analyses testify to the efficacy of four delivery systems.1 Although the ultimate goal of treatment is lifelong cessation , few trials have published results of abstinence beyond one year . Little consideration has therefore been given to whether the treatment is effective in reducing the major health risks of smoking . This effect would become evident only after many years of abstinence . Our r and omised trial showed that the use of nicotine nasal spray compared with a placebo spray was associated with more than double the number of abstainers at one year.2 We report the results from a longer term follow up to estimate the impact of relapse after one year on effectiveness . A total of 227 heavy smokers entered the trial ; 116 were given R and omised controlled trials are widely accepted as the most reliable method of determining effectiveness , but most trials have evaluated the effects of a single intervention such as a drug . Recognition is increasing that other , non-pharmacological interventions should also be rigorously evaluated.1 - 3 This paper examines the design and execution of research required to address the additional problems result ing from evaluation of complex interventions —that is , those “ made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper ( www.mrc.ac.uk/complex_packages.html ) . We focus on r and omised trials but believe that this approach could be adapted to other design s when they are more appropriate . # # # # Summary points Complex interventions are those that include several components The evaluation of complex interventions is difficult because of problems of developing , identifying , documenting , and reproducing the intervention A phased approach to the development and evaluation of complex interventions is proposed to help research ers define clearly where they are in the research process Evaluation of complex interventions requires use of qualitative and quantitative evidence There are specific difficulties in defining , developing , documenting , and reproducing complex interventions that are subject to more variation than a drug . A typical example would be the design of a trial to evaluate the benefits of specialist stroke units . Such a trial would have to consider the expertise of various health professionals as well as investigations , drugs , treatment guidelines , and arrangements for discharge and follow up . Stroke units may also vary in terms of organisation , management , and skill mix . The active components of the stroke unit may be difficult to specify , making it difficult to replicate the intervention . The box gives other examples of complex interventions . # # # # Examples of complex interventions Service delivery and organisation : Stroke units Hospital at home Interventions directed at health professionals ' behaviour : Strategies for implementing guidelines Computerised decision support Community interventions : Community This study compared 2 minimal interventions for reducing relapse in ex-smokers . One intervention involved 12-month access to a telephone hot line . In the other intervention , 8 relapse-prevention booklets were mailed to participants over 1 year . The 2 interventions were crossed in a 2 x 2 factorial design , yielding control , hot-line-only , mailings-only , and combined conditions . The criterion of at least 1 week of abstinence at baseline was met by 584 participants , 446 of whom also completed a 12-month assessment . Repeated mailings , but not the hot line , reduced relapse for those participants who had been abstinent for less than 3 months at baseline . At follow-up , 12 % of those in the mailings conditions were smoking again compared with 35 % in the nonmailing conditions . As predicted , both interventions were effective at attenuating the association between depressive symptoms and poor outcome found in the control condition Telephone counseling is a popular modality for smoking cessation treatment ; however , little attention has been paid to evaluating the efficacy of different contents of calls . This study compared 2 types of proactive telephone calls following a group program . Participants were r and omized to receive either : ( a ) basic content , consisting primarily of support ; or ( b ) enhanced content , tailored to the stage of cessation ( still smoking , abstinent , or relapsed ) and targeting factors hypothesized to be related to success ( motivation , self-efficacy , and negative mood ) . There was a significant interaction between treatment condition and gender . For men , the enhanced condition produced better abstinence rates through 15 months and lower relapse rates . For women , the basic condition was better . History of depression did not interact with condition OBJECTIVES To evaluate the effect of a provider counseling and office systems intervention in obstetric , pediatric , and Special Supplemental Nutrition Program for Women , Infants and Children ( WIC ) clinics on smoking and relapse rates in pregnant and postpartum women . METHODS Five community health centers were r and omized to special intervention ( SI ) or usual care ( UC ) . Subjects ( n = 601 ) were current smokers or had quit with pregnancy . Prenatal and postpartum interviews assessed smoking status and related factors . Data were collected between May 1997 and November 2000 . RESULTS There was a statistically significant difference in 30-day abstinence rates between SI ( 26 % ) and UC ( 12 % ) conditions at the end of pregnancy among women who had not quit spontaneously with pregnancy ( odds ratio [OR]=2.57 , p = 0.05 ) . This effect remained at 1 month postpartum but was lost at 3- and 6-month postpartum follow-ups . CONCLUSIONS Brief interventions delivered by healthcare providers during routine prenatal care increased smoking abstinence during pregnancy among women who did not quit spontaneously . Interventions extended into postpartum care did not affect relapse and smoking rates postdelivery This gender-specific research study compares the relative effectiveness of two theory-based interventions targeting women who smoke . Women with coronary artery disease ( CAD ; n = 53 ) or CAD risk factors ( n = 107 ) were r and omly assigned to either coping-skills Relapse Prevention ( RP ) treatment or an educational/supportive treatment based on Health Belief Model ( HBM ) principles . RP was comparable , but not superior to HBM treatment , as indicated by the lack of differential smoking outcomes at 3 and 6 months . RP was more effective than HBM for women with low self-efficacy , as predicted . The presence of a smoking-related disease had a substantial effect on smoking status , in that the odds of being abstinent at 6 months were 2.2 times greater for non-diagnosed women when compared with CAD women . These findings indicate that more potent relapse prevention interventions are needed to increase cessation rates in women who smoke , especially those with established heart disease The efficacy of a smoking cessation relapse prevention ( RP ) program , emphasizing cognitive-behavioral coping skills , was compared to that of a broad spectrum ( BS ) program , which emphasized behavioral skills . It was hypothesized that the RP program would be more effective in producing long-term abstinence , compared to the BS package . Abstinence rates vali date d by saliva thiocyanate and carbon monoxide , as well as self-report of smoking reduction , were measured at posttreatment , 3 and 6 months . No differences in posttreatment quit rates were found between the two groups , although both programs produced significantly higher quit rates than the wait-list control group . Contrary to prediction , the BS group produced marginally significantly greater abstinence at 3 months . No differences in abstinence were found at 6 months . Reduction in cigarette consumption was marginally significantly greater for the BS group at 3 and 6 months . Various mediators of treatment outcome were not found to influence success in quitting . There was a significant weight gain in those who quit OBJECTIVES Low-income women have high rates of smoking during pregnancy , but little is known about the costs , benefits , and cost-effectiveness of motivational interviewing ( MI ) , focused on the medical and psychosocial needs of this population , as an intervention for smoking cessation and relapse prevention . METHODS A sample of 302 low-income pregnant women was recruited from multiple obstetrical sites in the Boston metropolitan area into a r and omized controlled trial of a motivational intervention for smoking cessation and relapse prevention versus usual care ( UC ) . The findings of this clinical trial were used to estimate the costs , benefits , and cost-effectiveness of the intervention from a societal perspective , incorporating published quality -adjusted life-year ( QALY ) and life-year ( LY ) estimates . Outcomes included smoking cessation and relapse , maternal and infant outcomes , economic costs , LYs and QALYs saved , and incremental cost-effectiveness ratios . RESULTS The cost-effectiveness of MI for relapse prevention compared to UC was estimated to be $ 851/LY saved and $ 628/QALY saved . Including savings in maternal medical costs in sensitivity analyses result ed in cost savings for MI for relapse prevention compared to UC . For smoking cessation , MI cost more but did not provide additional benefit compared to UC . In one-way sensitivity analyses , the incremental cost-effectiveness of MI versus UC would have been $ 117,100/LY saved and $ 86,300/QALY saved if 8 % of smokers had quit . In two-way sensitivity analyses , MI was still relatively cost-effective for relapse prevention ( $ 17,300/QALY saved ) even if it cost as much as $ 2000/participant and was less effective . For smoking cessation , however , a higher level of effectiveness ( 9/110 ) and higher cost ( $ 400/participant ) result ed in higher incremental cost-effectiveness ratios ( $ 112,000/QALY ) . CONCLUSIONS Among low-income pregnant women , MI helps prevent relapse at relatively low cost , and may be cost-saving when net medical cost savings are considered . For smoking cessation , MI cost more but provided no additional benefit compared to UC , but might offer benefits at costs comparable to other clinical preventive interventions if 8 - 10 % of smokers are induced to quit While there was no statistical difference between the intervention and control groups , the overall relapse rate of 22 % ( 78 % nonsmoking ) , was lower compared to most of the published data from other studies . Results from the historical comparison group from the smoking cessation trial confirmed a 35 % relapse rate during pregnancy in this population |
2,228 | 23,606,848 | Available r and omized and nonr and omized studies indicate potential effectiveness of a cervical pessary in the prevention of preterm birth . | Introduction .
Reduction of preterm birth is a major goal in obstetric care .
We performed a systematic review of r and omized controlled trials and cohort studies on the effectiveness of the cervical pessary to prevent preterm birth . | OBJECTIVE To determine the effectiveness of cerclage pessary in the prevention of preterm birth in asymptomatic Chinese women with a short cervix at 20 to 24 weeks . METHODS Low-risk women carrying singleton pregnancies were screened with transvaginal ultrasound , and those with a cervical length < 25 mm at 20 to 24 weeks were recruited into a r and omized controlled trial , comparing the prophylactic use of cerclage pessary with expectant management . The analysis was by intent-to-treat . The primary outcome measure was preterm delivery before 34 weeks . RESULTS Among 4438 screened women , 203 women ( 4.6 % ) met the inclusion criteria and 108 ( 58 % ) consented for the study . A total of 53 and 55 women were allocated to pessary and control groups , respectively . There was no difference in background demographics , including the mean cervical length ( 19.6 mm versus 20.5 mm ) and the mean gestational age at r and omization ( both 21.9 weeks ) . Delivery before 34 weeks occurred in 9.4 % and 5.5 % ( p = 0.46 ) in the pessary and the control groups , respectively . No differences in major side effects were noted between the groups . CONCLUSION In our population , < 5 % had a cervical length of less than 25 mm at 20 to 24 weeks ' gestation . The prophylactic use of cerclage pessary did not reduce the rate of preterm delivery before 34 weeks Objective : The aim of this study was to evaluate the efficacy and safety of a noninvasive cerclage pessary in the management of cervical incompetence . Methods : This is a prospect i ve cohort study of all pregnant women treated for cervical incompetence during a 4-year period . Women with known risk factors for preterm delivery had transvaginal ultrasonography every 2–3 weeks after 17–19 weeks of gestation . Those with progressive shortening of cervix diagnosed before 30 weeks were treated with a cerclage pessary when the cervical length was ≤25 mm . The pessary was electively removed at 34–36 weeks . The course and outcome of pregnancy were recorded . Results : Thirty-two women were treated with a cerclage pessary . There were nine twin and two triplet pregnancies . Fifteen ( 47 % ) had two or more risk factors for preterm delivery . The mean gestational age at cerclage was 23 ( 17–29 ) weeks , cervical length 17 ( 5–25 ) mm . Two women required delivery before the onset of labor due to severe intrauterine growth restriction and one due to HELLP syndrome . These were excluded from further analysis . In the remaining 29 women , the interval between cerclage and delivery was 10.4 ( 2–19 ) weeks , mean gestational age at delivery 34 ( 22–42 ) weeks , and birth weight 2,255 ( 410–4,045 ) g. Thirteen ( 45 % ) women delivered before 34 weeks . There were a total of 35 live-born infants and four intrapartum fetal deaths ( all between 22 and 25 weeks gestation ) . All women complained of increased vaginal discharge , but no other significant complications were observed that could be attributed to the use of pessary . Conclusion : Cerclage pessary may be useful in the management of cervical incompetence . Whether it can be a noninvasive alternative to surgical cerclage merits further investigation BACKGROUND Most previous studies of the use of cervical pessaries were either retrospective or case controlled and their results showed that this intervention might be a preventive strategy for women at risk of preterm birth ; no r and omised controlled trials have been undertaken . We therefore undertook a r and omised , controlled trial to investigate whether the insertion of a cervical pessary in women with a short cervix identified by use of routine transvaginal scanning at 20 - 23 weeks of gestation reduces the rate of early preterm delivery . METHODS The Pesario Cervical para Evitar Prematuridad ( PECEP ) trial was undertaken in five hospitals in Spain . Pregnant women ( aged 18 - 43 years ) with a cervical length of 25 mm or less were r and omly assigned according to a computer-generated allocation sequence by use of central telephone in a 1:1 ratio to the cervical pessary or expectant management ( without a cervical pessary ) group . Because of the nature of the intervention , this study was not masked . The primary outcome was spontaneous delivery before 34 weeks of gestation . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00706264 . FINDINGS 385 pregnant women with a short cervix were assigned to the pessary ( n=192 ) and expectant management groups ( n=193 ) , and 190 were analysed in each group . Spontaneous delivery before 34 weeks of gestation was significantly less frequent in the pessary group than in the expectant management group ( 12 [ 6 % ] vs 51 [ 27 % ] , odds ratio 0·18 , 95 % CI 0·08 - 0·37 ; p<0·0001 ) . No serious adverse effects associated with the use of a cervical pessary were reported . INTERPRETATION Cervical pessary use could prevent preterm birth in a population of appropriately selected at-risk women previously screened for cervical length assessment at the midtrimester scan . FUNDING Instituto Carlos III Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Abstract Objective : The purpose was to determine the effect of vaginal pessaries in patients at risk for spontaneous preterm birth ( SPB ) . Study Design : Transvaginal sonography ( TVS ) was longitudinally performed to measure cervical length ( CL ) in 258 singleton at risk for SPB and 282 twin pregnancies . Pairs with or without treatment were matched for gestational age and the CL at examination . Results : In 4 singleton and 7 twin pregnancies the CL was < 15 mm before 24 weeks , the mean interval between pessary insertion and delivery was 13 + 2 and 12 + 5 weeks respectively . For the matched control analysis , 12 pairs with singleton and 23 pairs with twin pregnancies were compared . For singleton pregnancies , the mean interval between TVS and delivery was 99 ( 70–134 ) days in the treatment and 67 ( 2–130 ) days in the control group ( p = 0.0184 ) , the mean gestational age at delivery was 38 ( 36 + 6–41 ) and 33 + 4 ( 26–38 ) weeks respectively ( p = 0.02 ) . For twin pregnancies , the interval was 85 ( 43–129 ) days in the treatment and 67 ( 21–100 ) days in the control group ( p = 0.001 ) , gestational age at delivery was 35 + 6 ( 33–37 + 4 ) and 33 + 2 ( 24 + 4–37 + 2 ) respectively ( p = 0.02 ) . Within singleton pregnancies with pessary , there was no SPB < 36 weeks compared to 6/12 cases in the control group ( p < 0.001 ) . Within twin pregnancies , the rates were 8/23 cases with SPB < 36 weeks but none < 32 weeks , compared to 12/23 cases with SPB < 36 weeks and 7/23 cases < 32 weeks in the control group ( p < 0.001 ) . Conclusions : Insertion of a vaginal pessary may be a cost-effective preventive treatment in patients at risk for SPB . Prospect i ve controlled trials are needed BACKGROUND The role of the cervix in the pathogenesis of premature delivery is controversial . In a prospect i ve , multicenter study of pregnant women , we used vaginal ultrasonography to measure the length of the cervix ; we also documented the incidence of spontaneous delivery before 35 weeks ' gestation . METHODS At 10 university-affiliated prenatal clinics , we performed vaginal ultrasonography at approximately 24 and 28 weeks of gestation in women with singleton pregnancies . We then assessed the relation between the length of the cervix and the risk of spontaneous preterm delivery . RESULTS We examined 2915 women at approximately 24 weeks of gestation and 2531 of these women again at approximately 28 weeks . Spontaneous preterm delivery ( at less than 35 weeks ) occurred in 126 of the women ( 4.3 percent ) examined at 24 weeks . The length of the cervix was normally distributed at 24 and 28 weeks ( mean [ + /- SD ] , 35.2 + /- 8.3 mm and 33.7 + /- 8.5 mm , respectively ) . The relative risk of preterm delivery increased as the length of the cervix decreased . When women with shorter cervixes at 24 weeks were compared with women with values above the 75th percentile , the relative risks of preterm delivery among the women with shorter cervixes were as follows : 1.98 for cervical lengths at or below the 75th percentile ( 40 mm ) , 2.35 for lengths at or below the 50th percentile ( 35 mm ) , 3.79 for lengths at or below the 25th percentile ( 30 mm ) , 6.19 for lengths at or below the 10th percentile ( 26 mm ) , 9.49 for lengths at or below the 5th percentile ( 22 mm ) , and 13.99 for lengths at or below the 1st percentile ( 13 mm ) ( P < 0.001 for values at or below the 50th percentile ; P = 0.008 for values at or below the 75th percentile ) . For the lengths measured at 28 weeks , the corresponding relative risks were 2.80 , 3.52 , 5.39 , 9.57 , 13.88 , and 24.94 ( P < 0.001 for values at or below the 50th percentile ; P = 0.003 for values at the 75th percentile ) . CONCLUSIONS The risk of spontaneous preterm delivery is increased in women who are found to have a short cervix by vaginal ultrasonography during pregnancy To evaluate the efficiency of cerclage or pessary a prospect i ve r and om study has been done from 1982 to 1983 . Pelvic score of Bishop and tocolysis index of Baumgarten were used to define the situation at the beginning . Success has been estimated with help of neonatal parameters ( birth weight , Apgar score and RDS-morbidity ) and final gestational week . Both methods are equal in their effects Objective . The Arabin pessary may be beneficial in the treatment of cervical incompetence . The aim of the study was to analyse the efficacy of the treatment method of pregnant women with cervical incompetence . Methods . A non-r and omised study performed in the obstetrical wards in Lodz , Pol and utilising 54 pregnant women with cervical incompetence was developed to assess the efficiency of treatment methods of cervically incompetent women . These women were diagnosed by vaginal ultrasound examination during the course of the study . Patients with a cervical length of 15–30 mm before 28 weeks an Arabin cervical pessary were inserted , women whose cervical length was less than 15 mm were treated with cervical cerclage . The main end points of the study were preterm or term delivery . Results . In the Arabin pessary group , 1.9 % of women delivered before the 29th week of gestation and 83.3 % of women delivered after 37 weeks of pregnancy . Eighty-seven per cent of pregnant women treated for cervical incompetence by Arabin pessary delivered by normal spontaneous labour , 1.9 % delivered by forceps labour and 11.1 % of patients by caesarean section . Among pregnant women treated by Arabin pessary , 3.7 % of newborns were estimated as having a score of 0–4 on the Apgar scale , 13 % a score of 5–7 and 83.3 % a score of 8–10 . Conclusions . Cervical incompetence treatment effectively prolongs the duration of gestation . Application of the Arabin pessary is an effective method of cervical incompetence treatment |
2,229 | 25,742,618 | This meta- analysis suggests that the GSTM1 and GSTT1 null polymorphisms are not associated with the risk of hypertension . | BACKGROUND Some studies have recently focused on the association between glutathione S-transferase M1 ( GSTM1 ) and glutathione S-transferase T1 ( GSTT1 ) null polymorphisms and hypertension ; however , results have been inconsistent .
OBJECTIVE In order to drive a more precise estimation , the present systematic review and meta- analysis is performed to investigate the relationship between the GSTM1 and GSTT1 null polymorphisms and hypertension . | Several lines of evidence suggest that patients with essential hypertension have impaired endothelial nitric oxide activity and increased superoxide anion production . However , the mechanisms underlying these abnormalities remain unknown . We measured enzymatic superoxide dismutase ( SOD ) and glutathione peroxidase ( GPX ) activities in erythrocytes and whole blood , respectively , in 30 newly-diagnosed , normolipidaemic untreated mild hypertensive patients and in 164 age-matched healthy controls . SOD and GPX activities in hypertensive patients ( 806 ± 225 U/Hb.g and 5491 ± 2073 U/L , respectively ) were significantly lower than in the control group ( 931 ± 202 U/Hb.g and 6669 ± 1560 U/L , respectively ) ( P < 0.005 ) . no significant association was found between these antioxidant enzyme activities and blood pressure in normotensive controls . in the hypertensives , only log-transformed sod activity showed a significant negative correlation with systolic and diastolic blood pressure ( r = 0.37 , P < 0.05 ; r = 0.64 , P < 0.0001 , respectively ) . the low endogenous antioxidant enzyme activities observed may in turn result in decreased superoxide anion removal leading to nitric oxide inactivation |
2,230 | 23,842,691 | The prophylactic use of octreotide after PD does not result in a reduced incidence of POPF .
In conclusion , our findings suggest that the successful management of pancreatic anastomoses may depend more on the meticulous surgical technique , surgical volume , and other management parameters than on the type of technique used . | Over the past 100 years , advances in surgical techniques and perioperative management have reduced the morbidity and mortality after pancreaticoduodenectomy ( PD ) .
Many techniques have been proposed for the reconstruction of the pancreaticodigestive anastomosis to prevent the development of a postoperative pancreatic fistula ( POPF ) , but which is the best approach is still highly debated .
We carried out a systematic review to determine and compare the effectiveness of various methods of anastomosis after PD . | Objective : To compare the results of pancreaticogastrostomy versus pancreaticojejunostomy following pancreaticoduodenectomy in a prospect i ve and r and omized setting . Summary Background Data : While several techniques have been proposed for reconstructing pancreatico-digestive continuity , only a limited number of r and omized studies have been carried out . Methods : A total of 151 patients undergoing pancreaticoduodenectomy with soft residual tissue were r and omized to receive either pancreaticogastrostomy ( group PG ) or end-to-side pancreaticojejunostomy ( group PJ ) . Results : The 2 treatment groups showed no differences in vital statistics or underlying disease , mean duration of surgery , and need for intraoperative blood transfusion . Overall , the incidence of surgical complications was 34 % ( 29 % in PG , 39 % in PJ , P = not significant ) . Patients receiving PG showed a significantly lower rate of multiple surgical complications ( P = 0.002 ) . Pancreatic fistula was the most frequent complication , occurring in 14.5 % of patients ( 13 % in PG and 16 % in PJ , P = not significant ) . Five patients in each treatment arm required a second surgical intervention ; the postoperative mortality rate was 0.6 % . PG was favored over PJ due to significant differences in postoperative collection s ( P = 0.01 ) , delayed gastric emptying ( P = 0.03 ) , and biliary fistula ( P = 0.01 ) . The mean postoperative hospitalization period stay was comparable in both groups . Conclusions : When compared with PJ , PG did not show any significant differences in the overall postoperative complication rate or incidence of pancreatic fistula . However , biliary fistula , postoperative collection s and delayed gastric emptying are significantly reduced in patients treated by PG . In addition , pancreaticogastrostomy is associated with a significantly lower frequency of multiple surgical complications OBJECTIVE Pancreatic fistula is a leading cause of morbidity and mortality after pancreaticoduodenectomy . External drainage of pancreatic duct with a stent has been shown to reduce pancreatic fistula rate of pancreaticojejunostomy in a few retrospective or prospect i ve nonr and omized studies , but no r and omized controlled trial has been reported thus far . This single-center prospect i ve r and omized trial compared the results of pancreaticoduodenectomy with external drainage stent versus no stent for pancreaticojejunal anastomosis . METHODS A total of 120 patients undergoing pancreaticoduodenectomy with end-to-side pancreaticojejunal anastomosis were r and omized to have either an external stent inserted across the anastomosis to drain the pancreatic duct ( n = 60 ) or no stent ( n = 60 ) . Duct-to-mucosa anastomosis was performed in all cases . RESULTS The 2 groups were comparable in demographic data , underlying pathologies , pancreatic consistency , and duct diameter . Stented group had a significantly lower pancreatic fistula rate compared with nonstented group ( 6.7 % vs. 20 % , P = 0.032 ) . Radiologic or surgical intervention for pancreatic fistula was required in 1 patient in the stented group and 4 patients in the nonstented group . There were no significant differences in overall morbidity ( 31.7 % vs. 38.3 % , P = 0.444 ) and hospital mortality ( 1.7 % vs. 5 % , P = 0.309 ) . Two patients in the nonstented group and none in the stented group died of pancreatic fistula . Hospital stay was significantly shorter in the stented group ( mean 17 vs. 23 days , P = 0.039 ) . On multivariate analysis , no stenting and pancreatic duct diameter <3 mm were significant risk factors of pancreatic fistula . CONCLUSION External drainage of pancreatic duct with a stent reduced leakage rate of pancreaticojejunostomy after pancreaticoduodenectomy The effect of the long-acting somatostatin analogue S and ostatin ( SMS 201 - 995 ) on intestinal absorption and propagation ( mouth-to-caecum transit time ; MCTT ) , on pancreatic secretion and on gall bladder contraction after direct ( secretin-pancreozymin test ) and indirect stimulation ( Lundh meal ) , and on meal-induced responses of seven gastrointestinal regulatory peptides has been investigated . In a double-blind cross-over study , 9 healthy volunteers completed two 7-day periods with subcutaneous injections of either placebo or 25 micrograms SMS 201 - 995 twice daily . Mean faecal fat excretion was increased to 19.2 g/day and MCTT was three times longer during the SMS period . After duodenal infusion of a mixture containing D-galactose , D-xylose and triglycerides , SMS 201 - 995 significantly reduced the serum concentrations of D-galactose but increased serum levels of D-xylose . After 6 days of pretreatment , SMS 201 - 995 completely suppressed duodenal trypsin , lipase and bilirubin increases in response to endogenous stimulation by a Lundh meal . Concomitantly , cholecystokinin ( CCK ) release and gall bladder contraction were almost abolished . Compared with placebo , SMS 201 - 995 significantly diminished pancreatic amylase , trypsin and lipase output after stimulation with CCK , while the secretion of fluid and bicarbonate in response to secretin was unchanged . This inhibition of enzyme response was significantly more marked after a single injection of the analogue than after pretreatment for 7 days and did not reach the level of exocrine pancreatic insufficiency . CCK-induced gall bladder contraction was significantly inhibited by a single dose of 25 micrograms SMS 201 - 995 but not after 7 days of pretreatment with the somatostatin analogue Objective : This study compared the postoperative pancreatic anastomosis leakage rate of a new binding technique with the conventional technique of pancreaticojejunostomy after pancreaticoduodenectomy . Summary Background Data : Leakage from pancreatic anastomoses remains the single most important morbidity after pancreaticoduodenectomy and contributes to prolonged hospitalization and mortality . The reported incidence after conventional pancreaticojejunostomy ranged from 10 % to 29 % . We previously reported a new binding pancreaticojejunostomy technique with a leakage of 0 % . Methods : We conducted a prospect i ve r and omized study on 217 patients who underwent pancreaticoduodenectomy for benign and malignant diseases of the pancreatic head and the periampullary region comparing the 2 techniques of pancreaticojejunostomy . Results : Of the 111 patients r and omized to the conventional group , pancreaticojejunostomy leakage occurred in 8 patients , while no patient in the 106 patients r and omized to the binding group developed leakage ( & khgr;2 test , P = 0.014 ) . The overall postoperative complications developed in 41 patients ( 36.9 % ) in the conventional group compared with 26 patients ( 24.5 % ) in the binding group ( & khgr;2 test , P = 0.048 ) . Seven patients ( 6.3 % ) died in the perioperative period in the conventional group compared with 3 patients ( 2.8 % ) in the binding group ( & khgr;2 test , P = 0.37 ) . The postoperative hospital stay ( mean ± SD ) for the conventional group was 22.4 ± 10.9 days , which was significantly longer than the binding group ( 18.4 ± 4.7 days ) ( Mann-Whitney U test , P < 0.001 ) . Conclusions : Binding pancreaticojejunostomy after panceaticoduodenectomy significantly decreased postoperative complication and pancreaticojejunostomy leakage rates and shortened hospital stay when compared with conventional pancreaticojejunostomy Previous experimental studies have shown that multiple puncturing and stitching of the pancreas results in an increased pancreatic injury response . Furthermore , post-operative pancreatitis , which still is a largely under-diagnosed condition , appears to be an important mediator of many post-operative complications after pancreatic head resection . Stenting has been suggested to improve both short-term and long-term outcome after pancreaticojejunostomy . We have recently developed a biodegradable , radiopaque self-exp and ing stent , which has experimentally been shown suitable for pancreatobiliary applications . In this pilot study we tested the new technique for pancreatico-jejunostomy in 3 patients . In this novel anastomosis technique with a biodegradable stent the pancreatic stump is first sunk into the jejunum and tightened with a purse string in the bowel serosa , without any stitches through the pancreatic tissue , and the patency of the pancreatic duct is secured with a biodegradable stent against the compression of the tightened purse-string . The creation of anastomosis was possible as planned in all 3 patients . They all recovered without complications . The stent was seen in x-ray in all 3 during hospitilization , was found to have disappeared by 1 month in 2 patients , but was still in place at 3 months in 1 patient . The initial experiences described herein encourage progression to a phase I safety study , and later possibly to a phase II r and omized trial to test the efficacy of the new method BACKGROUND The reported pancreatic anastomosis fistula rate for pancreaticoduodenectomy , distal pancreatectomy , or enucleation is 2 % to 27 % . We hypothesized that reinforcement with a vascular pedicle would decrease the number of fistulas . We report a novel technique : the use of the round ligament of the liver to reinforce the pancreatic anastomosis after resection . STUDY DESIGN Patients undergoing resection from January 1 , 2000 until August 8 , 2005 , at a tertiary referral center , were followed in a retrospective cohort study . The round ligament of the liver was disconnected from the abdominal wall , from the umbilicus to the liver . After pancreatic resection , it was sutured to the anastomosis or closure . A pancreatic fistula was defined as follows : Jackson-Pratt ( JP ) drainage>50 mL/d , after the fifth postoperative day , with amylase>3 times the serum level ; reexploration for a fistula ; postoperative pseudocyst ; or death from sepsis with a presumed fistula . RESULTS In 95 patients , we were able to mobilize the round ligament and use it as a vascular pedicle . The overall fistula rate for the series was 5.3 % ( 5 of 95 ) and for pancreaticoduodenectomy it was 8.8 % ( 5 of 57 ) . There were no fistulas within the distal pancreatectomy and enucleation group ( n=38 ) . Importantly , there was no mortality from pancreatic fistula in the studied patients and no need for operative intervention for a fistula . CONCLUSIONS We present a novel technique to prevent pancreatic fistula . Although r and omized trials are necessary , it appears that the use of the round ligament as a vascular pedicle for reinforcing the pancreatic anastomoses and resections results in a very low number of pancreatic fistulas Pancreatic duct stenting remains an attractive strategy to reduce the incidence of pancreatic fistulas following pancreaticoduodenectomy ( PD ) with encouraging results in both retrospective and prospect i ve studies . We performed a prospect i ve r and omized trial to test the hypothesis that internal pancreatic duct stenting reduces the development of pancreatic fistulas following PD . Two hundred thirty-eight patients were r and omized to either receive a pancreatic stent ( S ) or no stent ( NS ) , and stratified according to the texture of the pancreatic remnant ( soft/normal versus hard ) . Four patients were excluded from the study ; in three instances due to a pancreatic duct that was too small to cannulate and in the other instance because a total pancreatectomy was performed . Patients who r and omized to the S group had a 6-cm-long segment of a plastic pediatric feeding tube used to stent the pancreaticojejunostomy anastomosis . In patients with a soft pancreas , 57 r and omized to the S group and 56 r and omized to the NS group . In patients with a hard pancreas , 58 r and omized to the S group and 63 r and omized to the NS group . The S and NS groups for the entire study population , as well as for the subgroup of high-risk patients with soft pancreata , were similar as regard to demographics , past medical history , preoperative symptoms , preoperative procedures , and intraoperative data . The pancreatic fistula rate for the entire study population was 9.4 % . The fistula rates in the S and NS subgroups with hard pancreata were similar , at 1.7 % and 4.8 % ( P=0.4 ) , respectively . The fistula rates in the S and NS subgroups with soft pancreata were also similar , at 21.1 % and 10.7 % ( P=0.1 ) , respectively . A nonstatistically significant increase in the pancreatic fistula rate in the S group persisted after adjusting for the operating surgeon and technical details of the operation ( e.g. , anastomotic technique , anastomotic orientation , pancreatic duct size , and number of intra-abdominal drains placed ) . In patients with soft pancreata , 63 % percent of the pancreatic fistulas in stented patients required adjustment to the clinical pathway ( including two deaths ) , compared to 47 % of the pancreatic fistulas in patients in the NS group ( P=0.3 ) . Internal pancreatic duct stenting does not decrease the frequency or the severity of postoperative pancreatic fistulas Intraabdominal bleeding , the most life-threatening complication following pancreaticoduodenectomy ( PD ) , most often is associated with failure of a pancreaticojejunostomy anastomosis or with intraabdominal infection . We investigated whether placement of an omental flap around the splanchnic vessels in PD could reduce the occurrence of intraabdominal bleeding and other postoperative complications . One hundred consecutive patients who underwent PD at the authors ’ institution between January 2000 and October 2004 were enrolled in this prospect i ve study . After dissection of the hepatoduodenal ligament , the major splanchnic arteries and the portal vein were covered by the omental flap . Preoperative condition , incidence of pancreatic fistula , intra-abdominal bleeding , other complications , treatment mortality , and hospital stay were analyzed for interrelationships . The frequency of pancreatic fistula ( 20 % ) differed little from those in previous reports . However , intraabdominal bleeding was observed in only 1 ( 1.0 % ) patient , who was considered to have too thin a flap . No intraabdominal abscess was encountered . No mortality or complications occurred in relation to the omental flap . Thus , wrapping an omental flap around dissected splanchnic vessels in PD reduced postoperative intraabdominal bleeding and infection , but failed to prevent pancreatic fistulas The aim of the present study was to evaluate the influence of low-dose perioperative octreotide on the prevention of complications ( pancreatic fistula and general complications ) in patients undergoing pancreatic surgery followed by pancreaticojejunostomy . A total of 105 patients were r and omized to receive either octreotide 0.1 mg subcutaneously 3 times/day for a total of 7 days or no octreotide . The primary endpoints were the occurence of a pancreatic fistula and or general complications , including extended length of hospital stay . There were 25 surgical draining procedures performed and 80 duodenopancreatectomies with or without preservation of the pylorus . In all , 25 ( 23.8 % ) of the patients were treated for chronic pancreatitis , 8 ( 7.6 % ) for benign tumoral disease , and 72 ( 68.6 % ) for carcinoma . All patients underwent pancreaticojejunostomy Objective The authors hypothesized that pancreaticogastrostomy is safer than pancreaticojejunostomy after pancreaticoduodenectomy and less likely to be associated with a postoperative pancreatic fistula . Summary Background Data Pancreatic fistula is a leading cause of morbidity and mortality after pancreaticoduodenectomy , occurring in 10 % to 20 % of patients . Nonr and omized reports have suggested that pancreaticogastrostomy is less likely than pancreaticojejunostomy to be associated with postoperative complications . Methods Between May 1993 and January 1995 , the findings for 145 patients were analyzed in this prospect i ve trial at The Johns Hopkins Hospital . After giving their appropriate preoperative informed consent , patients were r and omly assigned to pancreaticogastrostomy or pancreaticojejunostomy after completion of the pancreaticoduodenal resection . All pancreatic anastomoses were performed in two layers without pancreatic duct stents and with closed suction drainage . Pancreatic fistula was defined as drainage of greater than 50 mL of amylase‐rich fluid on or after postoperative day 10 . Results The pancreaticogastrostomy ( n = 73 ) and pancreaticojejunostomy ( n = 72 ) groups were comparable with regard to multiple parameters , including demographics , medical history , preoperative laboratory values , and intraoperative factors , such as operative time , blood transfusions , pancreatic texture , length of pancreatic remnant mobilized , and pancreatic duct diameter . The overall incidence of pancreatic fistula after pancreaticoduodenectomy was 11.7 % ( 17/145 ) . The incidence of pancreatic fistula was similar for the pancreaticogastrostomy ( 12.3 % ) and pancreaticojejunostomy ( 11.1 % ) groups . Pancreatic fistula was associated with a significant prolongation of postoperative hospital stay ( 36 ± 5 vs. 15 ± 1 days ) ( p < 0.001 ) . Factors significantly increasing the risk of pancreatic fistula by univariate logistic regression analysis included ampullary or duodenal disease , soft pancreatic texture , longer operative time , greater intraoperative red blood cell transfusions , and lower surgical volume ( p < 0.05 ) . A multivariate logistic regression analysis revealed the factors most highly associated with pancreatic fistula to be lower surgical volume and ampullary or duodenal disease in the resected specimen . Conclusions Pancreatic fistula is a common complication after pancreaticoduodenectomy , with an incidence most strongly associated with surgical volume and underlying disease . These data do not support the hypothesis that pancreaticogastrostomy is safer than pancreaticojejunostomy or is associated with a lower incidence of pancreatic fistula BACKGROUND Improving surgical quality of care requires accurate reporting of postoperative complications . STUDY DESIGN Accuracy of a prospect i ve surgical complication grading data base was assessed by performing a retrospective review of 204 pancreaticoduodenectomies ( PDs ) entered into the data base from January 1 , 2001 , to December 31 , 2003 . This up date d data base was then used to characterize 30-day morbidity and mortality after PD . RESULTS On review , 13 % of patients had a complication not identified in the prospect i ve complication data base , 8 % of patients had a complication reclassified , and 4 % of patients had a complication removed . At least 1 postoperative complication was experienced by 47 % of patients . After PD , 45 different complications occurred . Postoperative mortality at 30 days was 1 % , and 30-day readmission rate was 11 % . The 30-day reoperation rate was 9 % , and 14 % of patients required a percutaneous drainage procedure . Pancreatic anastomotic leak ( 12 % ) , wound infection ( 11 % ) , and delayed gastric emptying ( 7 % ) were the 3 most common postoperative complications , and all were associated with an increased length of stay . CONCLUSIONS Our prospect i ve surgical complication data base accurately characterized outcomes after PD and facilitated information gathering and analysis . The accuracy , efficiency , and reproducibility of a prospect i ve surgical complication data base favor its widespread use in postoperative complication reporting BACKGROUND Pancreatic fistula ( PF ) is one of the most common complications after pancreaticoduodenectomy . There have been no large prospect i ve r and omized trials evaluating PF rates comparing invagination versus duct to mucosa pancreaticojejunostomy . We tested the hypothesis that a duct to mucosa pancreaticojejunostomy would reduce the PF rate . STUDY DESIGN Between August 2006 and May 2008 , 197 patients at two institutions underwent pancreaticoduodenectomy by a total of 8 experienced pancreatic surgeons as part of this prospect i ve r and omized trial ( clinical trial no. NCT00359320 ) . All patients were stratified by pancreatic texture and r and omized to either an invagination or a duct to mucosa pancreaticojejunal anastomosis . Recorded variables included pancreatic duct diameter , operative time , blood loss , complications , and pathology . Primary end point was PF rate , as defined by the International Study Group on Pancreatic Fistula . Secondary end points included PF grade , postoperative length of hospital stay , other morbidities , and mortality . RESULTS Rate of PF for the entire cohort was 17.8 % . There were 23 fistulas ( 24 % ) in the duct to mucosa cohort and 12 fistulas ( 12 % ) in the invagination cohort ( p < 0.05 ) . The greatest risk factor for a PF was pancreas texture : PF developed in only 8 patients ( 8 % ) with hard gl and s , and in 27 patients ( 27 % ) with a soft gl and . There were two perioperative deaths ( both in the duct to mucosa group ) , with the proximate causes of death being PF , followed by bleeding and sepsis . CONCLUSIONS This dual-institution prospect i ve r and omized trial reveals considerably fewer fistulas with invagination compared with duct to mucosa pancreaticojejunostomy after pancreaticoduodenectomy . Results confirm increased PF rates in soft as compared with hard gl and s. Additional studies are needed to define the optimal technique of pancreatic reconstruction after pancreaticoduodenectomy BACKGROUND / AIMS This r and omized , placebo-controlled trial was analyzed in order to compare different methods of somatostatin administration in postoperative pancreatic fistula ( POPF ) and other postoperative complications following pancreaticoduodenectomy ( PD ) . METHODOLOGY Patients were r and omized to a control group ( n=32 ) and an experimental group ( n=35 ) . The primary endpoint was the incidences of POPF and other postoperative complications . The definition of POPF was classified as described by the International Study Group of Pancreatic Surgery . In the experimental group , the initial somatostatin was infused 1 day before operation and continued for 7 days after surgery . RESULTS The incidences of POPF did not show a significant difference between the 2 groups ( 11/30 , 36.7 % vs. 14/30 , 46.7 % ; p>0.385 ) . However , blood transfusion volume was 1.7±1.53U in the experimental group and 2.7±2.2U in the control group ( p=0.034 ) . Furthermore , the abdominal amylase concentration was significantly lower in the experimental group ( p=0.038 and p=0.043 , respectively ) in both Postoperative Day ( POD ) 3 and POD 7 . CONCLUSIONS Preoperative prophylactic use of somatostatin can not decrease the incidence of POPF and other complications after PD compared to postoperative use . However , the amylase concentration of the abdominal drainage and the blood transfusion volume seems to be decreased . Further experimental investigations are needed to estimate the value of preoperative use of somatostatin and clear the concrete mechanism Pancreaticogastrostomy ( PG ) after pancreaticoduodenectomy has been reported to have a lower incidence of pancreatic fistula than pancreaticojejunostomy ( PJ ) but this was not confirmed in a recent prospect i ve r and omized study The majority of lethal complications after pancreatic head resection are due to septic complications after leakage from the pancreatojejunostomy . Especially the smooth pancreatic remnant is prone to develop parenchymal leaks from shear forces applied during tying of the sutures . We developed a new mattress technique that avoids such shear forces , and we compared this method to the st and ard Cattell ( duct-to-mucosa ) technique . A total of 113 patients undergoing st and ard pancreatic head resection were prospect ively r and omized to receive either the st and ard Cattell anastomosis ( n = 56 ) or the new mattress technique ( n = 57 ) . All patients were evaluated for surgical and medical complications until discharge . Primary diagnosis and further demographic data compared well between the groups . The time to perform the mattress anastomosis was significantly shorter ( 15 vs. 22 minutes ; p < 0.0001 ) . The incidence of complications at the pancreatojejunostomy , and the length of hospital stay and survival were not significantly different between the two groups ; however , a trend toward more reoperations was noted in the Cattell group ( 10 vs. 5 ; p < 0.097 ) . The new mattress technique is simple , and our data show that the two techniques yield similar incidences of complications . Therefore the mattress technique for pancreatojejunostomy seems to be safe and is , in our opinion , well suitable for training schedules in pancreatic surgery BACKGROUND / AIMS Post-operative leakage from pancreatic anastomosis remains an important cause of morbidity in pancreaticoduodenectomy . It also contributes to prolonged hospitalization and mortality . We have developed a new inserting end-to -side pancreatico-jejunostomy without stiches on the pancreatic cut end or pancreatic duct . METHODOLOGY In this novel anastomosis technique , the pancreatic stump is first sunk into jejunum deeply in an end-to-side manner and tightened with a purse string in the bowel serosa . The pancreatic stump could be inserted completely inserting into the jejunum , independent of the size of the pancreas and jejunum . We performed this new anastomosis to 21 patients prospect ively in Kumamoto University Hospital from April to October in 2012 . RESULTS Postoperative pancreatic fistula was not observed at all in the 21 patients . There was no hospital death , whereas 6 patients developed postoperative complications . Importantly , one patient developed hemorrhage from pancreatic cut end into the jejunum . CONCLUSIONS This new method would be expected to minimize leakage from pancreaticojejunostomy . Further studies should be planned in a r and omized controlled trial compared with another traditional pancreatico-jejunostomy BACKGROUND / AIMS During the recent years we have developed and experimentally tested a biodegradable stent for pancreatobiliary applications . Such stents may be used in benign strictures or when securing the flow of bile , pancreatic juice or a fluid collection after endoscopic or surgical procedures . The lack of suitable devices has so far prohibited clinical endoscopic or percutaneous tests whereas surgical application has become possible . Recently we described a modified binding ( purse string ) pancreaticojejunostomy , where a biodegradable stent is introduced to secure the lumen opening when tightening the bowel over the pancreas with a purse string . Although routine use of any stent in pancreaticojejunostomy has been under debate , we used this setting to run for the first phase I human clinical trial with a biodegradable stent in a pancreatobiliary application . METHODS After 29 pancreaticoduodenectomies , a braided gamma sterilized radiopaque 96L/4D polylactide stent was introduced into the duct of pancreas remnant , which was then sunk into the Roux-Y jejunal limb . Complications , stent disappearance and late anastomotic patency ( MRI ) were monitored . RESULTS Hospital mortality was zero . One patient developed Grade C fistula ( overall fistula rate 3 % ) . She also developed Grade C hemorrhage and Grade C delayed gastric emptying ( DGE ) . One other patient developed Grade B hemorrhage ( overall hemorrhage rate 7 % ) and B DGE . Three other patients developed clinical ly significant Grade B-C DGE ( 5/29=17 % ) . In addition , 10 other patients were not on solid food only on post-operative day 8 , and were classified as Grade A DGE ( 34 % ) . Most of these patients were eating normally and could be discharged from hospital by day 10 . Nine out of 26 patients ( 35 % ) with negative preoperative trypsinogen test , developed post-operative trypsinogen release suggesting pancreatitis . Within 12 months four patients died and one quitted the study . The stents disappeared in median 3 months . MRI interpretation of the anastomosis failed in one patient having ascites . Of the 23 patients , 13 ( 57 % ) had the anastomosis well open , three ( 13 % ) had some narrowing , while seven ( 30 % ) had the anastomosis obstructed . CONCLUSION Compared with our previous experiences obtained in pancreaticoduodenectomy , a biodegradable stent is well tolerated in the human pancreatic duct , encouraging further development for future applications and tests in r and omized trials BACKGROUND / AIMS This is a non-r and omized comparative trial design ed to compare the results of pancreaticoduodenectomy with internal pancreatic stenting versus no stenting for pancreaticojejunal ( PJ ) anastomosis after pancreaticoduodenectomy . METHODOLOGY Between January 1999 and March 2008 , a total of 49 consecutive patients undergoing pancreaticoduodenectomy with duct-to-mucosa PJ anastomosis with , or without an internal stent were evaluated . RESULTS The 2 groups were comparable in demographic data , underlying pathologies , and pancreatic stump condition . Four patients ( 16.7 % ) in the stented group , and four patients ( 16 % ) in the non-stented anastomosis group had pancreatic fistula . There was no significant difference in pancreatic fistula rate between two groups . No surgical reintervention was necessary in all the patients with pancreatic fistulas . There were also no significant differences in operating time ( mean , 270.5 minutes vs. 263.6 minutes ) , intra-operative blood loss ( mean , 772.9 ml vs. 665.3 ml ) , overall morbidity ( 45.8 % vs. 40 % ) and hospital mortality ( 4.2 % vs. 4.0 % ) . The mean hospital stay after surgery was 34 days in stented group and 21.5 days in non-stented group . CONCLUSIONS Internal stenting of pancreatic duct could not reduce pancreatic fistula rate after pancreaticoduodenectomy BACKGROUND Only 2 large ( more than 100 patients ) prospect i ve trials comparing pancreatogastrostomy ( PG ) with pancreatojejunostomy ( PJ ) after pancreatoduodenectomy ( PD ) have been reported until now . One nonr and omized study showed that there were less pancreatic and digestive tract fistula with PG , whereas the other , a r and omized trial from a single high-volume center , found no significant differences between the two techniques . METHODS Single blind , controlled r and omized , multicenter trial . The main endpoint was intra-abdominal complications ( IACs ) . RESULTS Of 149 r and omized patients , 81 underwent PG and 68 PJ . No significant difference was found between the two groups concerning pre- or intraoperative patient characteristics . The rate of patients with one or more IACs was 34 % in each group . Twenty-seven patients sustained a pancreatoenteric fistula ( 18 % ) , 13 in PG ( 16 % ; 95 % confidence interval [ CI ] 8 - 24 % ) and 14 in PJ ( 20 % ; 95 % CI 10.5 - 29.5 % ) . No statistically significant difference was found between the 2 groups concerning the mortality rate ( 11 % overall ) , the rate of reoperations and /or postoperative interventional radiology drainages ( 23 % ) , or the length of hospital stay ( median 20.5 days ) . Univariate analysis found the following risk factors : ( 1 ) age > or = 70 years old , ( 2 ) extrapancreatic disease , ( 3 ) normal consistency of pancreas , ( 4 ) diameter of main pancreatic duct <3 mm , ( 5 ) duration of operation > 6 hours , and ( 6 ) a center effect . Significantly more IAC , pancreatoenteric fistula , and deaths occurred in one center ( that included the most patients ) ( P = .05 ) , but there were significantly more high-risk patients in this center ( normal pancreas consistency , extrapancreatic pathology , small pancreatic duct , higher transfusion requirements , and duration of operation > 6 hours ) compared with the other centers . In multivariate analysis , the center effect disappeared . Independent risk factors included duration of operation > 6 hours for IAC and for pancreatoenteric fistula ( P = .01 ) , extrapancreatic disease for pancreatoenteric fistulas ( P < .04 ) , and age > or = 70 years for mortality ( P < .02 ) . CONCLUSIONS The type of pancreatoenteric anastomosis ( PJ or PG ) after PD does not significantly influence the rate of patients with one or more IAC and /or pancreatic fistula or the severity of complications Objective : To compare the results of postoperative morbidity rate of a new pancreatogastrostomy technique , pylorus-preserving pancreaticoduodenectomy ( PPPD ) with gastric partition ( PPPD-GP ) with the conventional technique of pancreaticojejunostomy ( PJ ) . Summary and Background Data : Pancreatojejunostomy and pancreatogastrostomy ( PG ) are the commonly preferred methods of anastomosis after pancreatoduodenectomy ( PD ) . All r and omized controlled trials failed to show advantage of a particular technique , suggesting that both PJ and PG provide equally results . However , postoperative morbidity remains high . The best technique in pancreatic anastomosis is still debated . Method : Described here is a new technique , PPPD-GP ; in this technique the gastroepiploic arcade is preserved . Gastric partition was performed using 2 endo-Gia staplers along the greater curvature of the stomach , 3 cm from the border . This gastric segment , 10 to 12 cm in length is placed in close proximity to the cut edge of the pancreatic stump . An end-to-side , duct-to-mucosa anastomosis ( with pancreatic duct stent ) is constructed . One hundred eight patients undergoing PPPD for benign and malignant diseases of the pancreatic head and the periampullary region were r and omized to receive PG ( PPPD-GP ) or end-to-side PJ ( PPPD-PJ ) . Results : The two treatment groups showed no differences in preoperative parameters and intraoperative factors . The overall postoperative complications were 23 % after PPPD-GP and 44 % after PPPD-PJ ( P < 0.01 ) . The incidence of pancreatic fistula was 4 % after PPPD-GP and 18 % after PPPD-PJ ( P < 0.01 ) . The mean + SD hospital stay was 12 ± 2 days after PPPD-GP and 16 ± 3 days after PPPD-PJ . Conclusions : This study shows that PPPD-GP can be performed safely and is associated with less complication than PPPD-PJ . The advantage of this technique over other PG techniques is that the anastomosis is outside the area of the stomach where the contents empty into the jejunum , but pancreatic juice drains directly into the stomach Aim This study ’s aim is to evaluate the effectiveness of using an internal stent when fashioning a duct-to-mucosa pancreatojejunostomy on preventing pancreatic fistula formation , as well as on the overall outcome for patients undergoing pancreaticoduodenectomy . Material s and methods Between January 2000 and December 2008 , 82 consecutive patients underwent pancreaticoduodenectomy and duct-to-mucosa pancreaticojejunostomy in an isolated jejunal loop , either with or without the aid of an internal stent . The allocation of the patients into group A ( n = 41 , stented anastomosis ) and group B ( n = 41 , unstented anastomosis ) was performed in a strictly alternating way . No statistically significant differences were identified between the two groups regarding age , sex , operative time , intraoperative pathological findings , and comorbidities . The two groups were compared regarding the rate of pancreatic fistula formation , postoperative complications , and hospital stay . Results In group A , pancreatic fistula formation rate was 4.9 % ; overall morbidity reached 30 % ; and hospital stay duration was 13 ± 4 days . In group B , pancreatic fistula formation rate was 2.4 % ; overall morbidity was 26 % ; and hospital stay duration extended to 14 ± 5 . According to Clavien ’s classification , the severity of surgical complications was design ated as follows : for group A , 56 % of the complications were allocated as grade I , 38 % grade II , 4 % grade III , 2.5 % grade IV , and 0 % grade V. The relative values for group B were 53 % , 42 % , 3 % , 2 % , and 0 % , respectively . In six group A patients ( 14.7 % ) , the internal stent was found stuck in the pancreatic stump , causing severe back pain requiring analgesic treatment with opioids for four of them . In group B , four patients ( 9.7 % ) complained of mild back pain , none of which required regular treatment . No mortalities were recorded in both groups . No statistically significant differences were found between the two groups regarding fistula formation and severity of complications . Conclusions Internal stenting of a duct-to-mucosa pancreatojejunostomy does not diminish the rate of pancreatic fistula formation or alter overall patient ’s outcome Objective Using a prospect i ve r and omized study to assess postoperative morbidity and pancreatic function after pancreaticoduodenectomy with pancreaticojejunostomy and duct occlusion without pancreaticojejunostomy . Summary Background Data Postoperative complications after pancreaticoduodenectomy are largely due to leakage of the pancreaticoenterostomy . Pancreatic duct occlusion without anastomosis of the pancreatic remnant may prevent these complications . Methods A prospect i ve r and omized study was performed in a nonselected series of 169 patients with suspected pancreatic and periampullary cancer . In 86 patients the pancreatic duct was occluded without anastomosis to pancreatic remnant , and in 83 patients a pancreaticojejunostomy was performed after pancreaticoduodenectomy . Postoperative complications were the endpoint of the study . All relevant data concerning patient demographics and postoperative morbidity and mortality as well as endocrine and exocrine function were analyzed . At 3 and 12 months after surgery , evaluation of weight loss , stools , and the use of antidiabetics and pancreatic enzyme was repeated . Results Patient characteristics were comparable in both groups . There were no differences in median blood loss , duration of operation , and hospital stay . No significant difference was noted in postoperative complications , mortality , and exocrine insufficiency . The incidence of diabetes mellitus was significantly higher in patients with duct occlusion . Conclusions Duct occlusion without pancreaticojejunostomy does not reduce postoperative complications but significantly increases the risk of endocrine pancreatic insufficiency after duct occlusion Postoperative pancreatic fistula ( POPF ) remains one of the most common causes of morbidity following pancreaticoduodenectomy ( PD ) . This r and omized trial examined whether external stent drainage of the pancreatic duct decreases the rate of POPF after PD and subsequent pancreaticojejunostomy ( PJ ) Somatostatin inhibits gastroenteropancreatic exocrine secretion and is often used after pancreaticoduodenectomy to reduce pancreatic secretion to minimize tissue damage and pancreatic stump complications . Because our earlier clinical work saw a major increase in delayed gastric emptying ( DGE ) with somatostatin prophylaxis after pylorus-preserving pancreaticoduodenectomy ( PPPD ) , this small-group study was design ed to confirm or disprove that observation . From August 1997 to December 2000 , a total of 23 post-PPPD patients were r and omized to receive somatostatin prophylaxis [ somatostain ( + ) ] ( n = 11 ) or not [ somatostatin ] ( − ) ( n = 12 ) . The incidence of DGE , scintographic solid-phase emptying results on day 14 postoperatively , and sequential fasting plasma motilin levels were compared , as motilin levels are related to both gastric motility and somatostatin levels . The somatostatin(+ ) group exhibited greatly increased patient complaints of DGE : 9 of 11 ( 82 % ) versus 3 of 12 ( 25 % ) in the somatostatin(− ) group . Radiologic scintography showed somatostatin prophylaxis prolonged the half-time ( T1/2 ) of solid-phase emptying : 144.5 ± 51.4 minutes for somatostatin(+ ) versus 89.0 ± 59.9 minutes for somatostatin(− ) ( p < 0.001 ) . Comparing pre-PPPD and post-PPPD plasma motilin levels prior to somatostatin infusion , motilin decreased 80 % in reaction to the surgery . For somatostatin(− ) patients , motilin levels oscillated , or “ rang , ” postoperatively , reaching a higher level on day 3 , declined to a new record minimum on day 7 , and by day 21 were 50 % of the original and the slope of the recovery curve was increasing well . In somatostatin(+ ) patients the same ringing pattern was observed but decreased with motilin levels 30 % to 70 % lower than in the somatostatin(− ) patients . By day 21 somatostatin(+ ) motilin levels were recovering but still only 20 % original levels , and the slope of the recovery curve was not optimistic . On postoperative day 14 the plasma motilin levels ( below approximately 6 bg/ml ) correlated strongly with DGE for both groups . Despite the small sample size , the results indicated that ( 1 ) somatostatin prophylaxis significantly decreases fasting plasma motilin ; ( 2 ) somatostatin prophylaxis produces lingering suppression of plasma motilin ; ( 3 ) PPPD surgery itself significantly reduces fasting motilin levels with recovery to 50 % normal at day 21 ; ( 4 ) the mechanism of somatostatin-induced DGE seems related to reduced fasting plasma motilin levels BACKGROUND A stent often is placed across the pancreaticojejunostomy . However , there is no report compared between internal drainage and external drainage . METHODS We conducted a prospect i ve r and omized trial ( NCT00628186 registered at http:// Clinical Trials.gov ) with 100 patients who underwent pancreaticoduodenectomy and we compared the effects on postoperative course . RESULTS The incidence of pancreatic fistula according to the International Study Group on Pancreatic Fistula criteria was not different ( external , 20 % ; vs internal , 26 % ) , and the incidence of the other complications was similar between stent types . The median postoperative hospital stay was 21 days ( range , 8 - 163 d ) in the internal drainage group , which was shorter than the median stay of 24 days ( range , 21 - 88 d ) in the external drainage group ( P = .016 ) . CONCLUSIONS Both internal drainage and external drainage were safety devices for pancreaticojejunostomy . Internal drainage simplifies postoperative managements and it might shorten postoperative stay for pancreaticoduodenectomy Objectives : We prospect ively investigated the efficacy of an external pancreatic duct stent to prevent pancreatic fistula in the nonfibrotic pancreas after pancreaticojejunostomy , in which the degree of pancreatic fibrosis was assessed objective ly by using dynamic magnetic resonance imaging ( MRI ) . Methods : Among the 67 consecutive patients who underwent pancreatic head resection , 45 patients were judged to have a normal pancreas without fibrosis based on the preoperative assessment of pancreatic fibrosis based on MRI . The patients were r and omly allocated to 1 of 2 groups with ( n = 23 ) or without ( n = 22 ) use of an external pancreatic duct stent in performing a pancreaticojejunostomy . Results : Pancreatic fistula developed in 8 ( 34.5 % ) patients in the stented group : 3 grade A and 5 grade B ; whereas in the nonstented group , 9 ( 40.9 % ) patients developed pancreatic fistula : 3 grade A and 6 grade B. There were no significant differences in the incidence or severity of pancreatic fistula between the 2 groups . Conclusions : The utility of the external pancreatic duct stent after pancreaticojejunostomy was not found in the nonfibrotic pancreases , which were sorted according to the degree of pancreatic fibrosis using the pancreatic time-signal intensity curve analysis from MRI AIMS To evaluate the impact of prophylactic octreotide on gastric emptying in patients undergoing pancreaticoduodenectomy . Postoperative pancreatic fistula ( POPF ) and delayed gastric emptying ( DGE ) are common complications after pancreaticoduodenectomy . Whereas several prospect i ve r and omized trials propose the prophylactic use of octreotide to prevent pancreatic fistula formation , somatostatin has , however , been associated with delayed gastric emptying after partial duodenopancreatectomy . METHODS In this prospect i ve , r and omized , double-blinded , placebo-controlled trial we analyzed the influence of prophylactic octreotide on delayed gastric empting after pancreaticoduodenectomy . Patients were r and omized to the placebo group ( n=32 ) and the octreotide group ( n=35 ) . Primary endpoint was the incidence of delayed gastric emptying , secondary endpoints included perioperative morbidity other than DGE . DGE was measured by clinical signs , gastric scintigraphy and the hydrogen breath test . Risk factors for DGE other than octreotide were analyzed by univariate and multivariate analyses . RESULTS DGE measured by clinical signs was similar between both groups studied ( approximately 20 % of the patients ) . Gastric scintigraphy ( T(1/2 ) ) was 76.3+/-15.2 min in the octreotide group and 86.7+/-18.0 min in controls at day 7 , respectively . The H(2 ) breath test was 65.0+/-6.5 min in octreotide treatment group and 67.0+/-5.7 min in controls at day 8 . POPF grade C occurred in approximately 3 % of the patients , although prophylactic treatment of octreotide did not reduce the incidence of POPF . Multivariate analysis showed that postoperative intraabdominal bleeding and infection were independent risk factors for DGE . Furthermore preoperative biliary stenting reduced postoperative DGE after partial duodenopancreatectomy . CONCLUSION Prophylactic octreotide has no influence on gastric emptying and does not decrease the incidence of postoperative pancreatic fistula after pancreaticoduodenectomy |
2,231 | 23,897,930 | The psychosocial support of PR contributes to the patients ’ strength and desire for participation and the health education leads to illness-perception learning .
Both psychosocial support and health education develop patients ’ empowerment , while PR promotes opportunities to health transitions .
The empowerment experienced by the patients in taking advantage of these opportunities leads to positive impacts over time .
If they do not exploit these occasions , negative impacts arise in their life , which make the treatment assistance or follow-up more difficult .
The COPD patients ’ feedback revealed that PR promotes a better ‘ way of life ’ , well-being and important behavioural changes towards health promotion | The aim of this study was to give an in-depth consideration of the chronic obstructive pulmonary disease ( COPD ) patients ’ subjective view of the impact of pulmonary rehabilitation ( PR ) on their lives . | Objective To evaluate an entirely outpatient-based program of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease COPD , using St . George ’s Respiratory question naire ( SGRQ ) , the 6-minutes walking test ( 6-MWT ) and BODE index as the primary outcome measures . Methods A prospect i ve , parallel-group controlled study of an outpatient rehabilitation program in 80 patients with COPD ( 67 men and 13 women ; mean age 64.8 ± 10.6 years ; FEV1 , 42.8 % ± 7.6 % of the predicted value . The active group ( n = 40 ) took part in a 14-week rehabilitation program [ 3 h/wk , 1.5 h of education and exercise and 1.5 h of cycling ] . The control group ( n = 40 ) was review ed routinely as medical out patients . The following evaluations were carried out at study entry and after14 weeks : ( 1 ) pulmonary function studies ; ( 2 ) 6-minutes walking test 6MWT ; ( 3 ) quality of life ; and ( 4 ) BODE index . Results The following patients completed the study : 35 patients ( 87.5 % ) from the active group ( mean age , 63.7 ± 11.9 years ; mean forced expiratory volume in one second ( FEV1 ) , 41.9 ± 2.6 % of the predicted value ) ; and 36 patients ( 88 % ) from the control group ( mean age , 65.9 ± 10.3 years ; mean FEV1 , 43.33 ± 3.6 % of the predicted value ) . We found no changes in pulmonary function parameters in the active group and the control one at 14weeks . On the other h and , there were significant changes within the components of the SGRQ ( 12.3 for the score total ) for the patients of the active group but not for the patients of the control one ( only 1.5 for the score total ) , we observed also a significant increase in the distance of the 6-MWT in the patients of the active group but not for the patients of the control one , and finally a decrease of two points ( from 6 to 4 ) was noted in the score of the active group ’s BODE index without any change in the control group ’s one . Conclusion An outpatient-based of 14-week rehabilitation program significantly improved the quality of life and exercise tolerance without any change in the pulmonary function in patients with moderate COPD , and there was also a large decrease in the risk of death in rehabilitated patients as measured using the BODE index Background Recently , there has been a surge of international interest in combining qualitative and quantitative methods in a single study – often called mixed methods research . It is timely to consider why and how mixed methods research is used in health services research ( HSR ) . Methods Documentary analysis of proposals and reports of 75 mixed methods studies funded by a research commissioner of HSR in Engl and between 1994 and 2004 . Face-to-face semi-structured interviews with 20 research ers sample d from these studies . Results 18 % ( 119/647 ) of HSR studies were classified as mixed methods research . In the documentation , comprehensiveness was the main driver for using mixed methods research , with research ers wanting to address a wider range of questions than quantitative methods alone would allow . Interviewees elaborated on this , identifying the need for qualitative research to engage with the complexity of health , health care interventions , and the environment in which studies took place . Motivations for adopting a mixed methods approach were not always based on the intrinsic value of mixed methods research for addressing the research question ; they could be strategic , for example , to obtain funding . Mixed methods research was used in the context of evaluation , including r and omised and non-r and omised design s ; survey and fieldwork exploratory studies ; and instrument development . Studies drew on a limited number of methods – particularly surveys and individual interviews – but used methods in a wide range of roles . Conclusion Mixed methods research is common in HSR in the UK . Its use is driven by pragmatism rather than principle , motivated by the perceived deficit of quantitative methods alone to address the complexity of research in health care , as well as other more strategic gains . Methods are combined in a range of context s , yet the emerging method ological contributions from HSR to the field of mixed methods research are currently limited to the single context of combining qualitative methods and r and omised controlled trials . Health services research ers could further contribute to the development of mixed methods research in the context s of instrument development , survey and fieldwork , and non-r and omised evaluations Background Pulmonary rehabilitation ( PR ) is recognized as an evidence -based treatment in improving dyspnea and quality of life in patients with COPD . We evaluated the number needed to treat ( NNT ) to achieve an increase in physical capacity , as defined by a significant improvement in the six-minute walk test ( 6MWT ) in patients with COPD undergoing PR . Methods The study enrolled 284 patients aged 41 to 86 years ( mean age 69.4 years ) divided into two groups : a study group ( 222 patients ) undergoing a PR program , and a control group ( 62 patients ) treated only with drugs . The study group included patients with COPD divided in four subgroups according to GOLD stages . Results In the study group , 142 out of 222 patients ( 64 % ) had an increase of at least 54 m in the 6MWT following PR versus 8 out of 62 patients ( 13 % ) in the control group after the same time interval . The NNT in the overall study group was 2 ; the same NNT was obtained in GOLD stages 2 , 3 , and 4 , but was 8 in stage 1 . Conclusions PR is highly effective in improving the exercise capacity of patients with COPD , as demonstrated by a valuable NNT , with better results in patients with a more severe disease BACKGROUND : A key component in the management of chronic obstructive pulmonary disease ( COPD ) patients is pulmonary rehabilitation ( PR ) , the corner stone of which is exercise training . AIM : This study aims to evaluate the effect of a two-months , home-based PR program with outpatient supervision every two weeks , on exercise tolerance and health-related quality of life ( HRQL ) using Arabic-translated st and ardized generic and specific question naires in COPD patients recently recovered from acute exacerbation , DESIGN : R and omized clinical trial . SETTING AND SUBJECTS : A total of 39 COPD patients who recovered from acute exacerbation were r and omly allocated either a two-month home-based PR program in addition to st and ard medical therapy or st and ard medical therapy alone in the period between July 2008 and March 2009 . METHODS : Pulmonary function tests ( PFTs ) , six-minute walk distance ( 6-MWD ) test , Arabic-translated chronic respiratory disease question naire-self administered st and ardized format ( CRQ-SAS ) and quality of life scale Short Form ( SF-36 ) were compared between 25 patients with moderate to severe COPD who underwent a two-month PR program ( group 1 ) and 14 COPD patients who did not ( group 2 ) . RESULTS : Group 1 showed significant improvement in the 6-MWD , and HRQL scores at two months compared with the usual care patients in group 2 ( P less than 0.05 ) . Improvement in both CRQ-SAS and SF-36 scores were statistically significant and comparable in group 1 . CONCLUSION : The supervised , post discharge , two-month home-based PR program is an effective non pharmacological intervention in the management of stable patients with COPD . The 6-MWD is a simple , inexpensive and safe test to assess physical and functional capabilities among COPD patients . HRQL can be measured in patients with COPD either by disease-specific tools that have been specifically design ed for use in patients with respiratory system disorders or by generic HRQL tools that can be used across population s with a variety of medical conditions . The Arabic-translated CRQ-SAS is a new tool for assessment of Arabic-speaking patients with chronic respiratory diseases OBJECTIVE To examine the effect of an inpatient pulmonary rehabilitation program on functional outcome , supplemental oxygen use , quality of life ( QOL ) , and rehospitalization . DESIGN A prospect i ve study . SETTING Inpatient pulmonary rehabilitation unit . PATIENTS One hundred fifty-seven patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) admitted to an inpatient pulmonary rehabilitation program over a 3-year period . INTERVENTION Comprehensive interdisciplinary inpatient pulmonary rehabilitation program with an average length of stay of 21 days . MAIN OUTCOME MEASURES Improvements in QOL question naire scores , COPD knowledge question naire scores , 6-minute walking test ( with 3 ambulation categories : bed-bound , household ambulators , community ambulators ) , and supplemental oxygen use . Rehospitalization 1 year after completion of the program was also assessed and compared with hospital days for the year before the program . RESULTS On discharge from the program , 88 % of individuals walked farther ( p < .0001 ) , and community ambulators doubled their walking distance , whereas bed-bound patients decreased 10-fold ; supplemental oxygen use dropped 33 % during the day ( p < .0001 ) and 57 % during the night ( p < .0001 ) ; 82 % showed improved QOL ( p < .0001 ) ; 67 % showed improved knowledge of COPD ( p < .0001 ) ; and 67 % of the sample spent less time in the hospital during the 12 months after program completion compared with the 12 months before admission ( p < .001 ) . CONCLUSIONS An inpatient pulmonary rehabilitation program leads to improved endurance and functional ambulation , decreased supplemental oxygen use , and fewer hospitalizations 1 year after discharge for patients with COPD |
2,232 | 16,235,299 | Dietary advice appears to be effective in bringing about modest beneficial changes in diet and cardiovascular risk factors over approximately 9 months but longer term effects are not known | BACKGROUND Changes in population diet are likely to reduce cardiovascular disease and cancer , but the effect of dietary advice is uncertain .
OBJECTIVES To assess the effects of providing dietary advice to achieve sustained dietary changes or improved cardiovascular risk profile among healthy adults . | Despite formal recommendations for dietary change to reduce the incidence of ischaemic heart disease , the acceptability and effectiveness of the proposed diets have not been well investigated in population based studies . In this preliminary investigation of nutritional advice in a well population , subjects in one group practice were r and omized to receive either dietary instruction or simple follow up without instruction . The dietary recommendations were well received , and a substantial proportion of subjects reported altering their diets in accordance with them . There were modest beneficial changes in plasma lipid levels among men . Thus , using general practice as an avenue for promoting dietary change is feasible , and may be effective among men 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 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 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 BACKGROUND We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas , which are precursors of most large-bowel cancers . METHODS We r and omly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before r and omization to one of two groups : an intervention group given intensive counseling and assigned to follow a diet that was low in fat ( 20 percent of total calories ) and high in fiber ( 18 g of dietary fiber per 1000 kcal ) and fruits and vegetables ( 3.5 servings per 1000 kcal ) , and a control group given a st and ard brochure on healthy eating and assigned to follow their usual diet . Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps ; they remained in the study for approximately four years , undergoing colonoscopy one and four years after r and omization . RESULTS A total of 1905 of the r and omized subjects ( 91.6 percent ) completed the study . Of the 958 subjects in the intervention group and the 947 in the control group who completed the study , 39.7 percent and 39.5 percent , respectively , had at least one recurrent adenoma ; the unadjusted risk ratio was 1.00 ( 95 percent confidence interval , 0.90 to 1.12 ) . Among subjects with recurrent adenomas , the mean ( + /-SE ) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group . The rate of recurrence of large adenomas ( with a maximal diameter of at least 1 cm ) and advanced adenomas ( defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high- grade dysplasia , including carcinoma ) did not differ significantly between the two groups . CONCLUSIONS Adopting a diet that is low in fat and high in fiber , fruits , and vegetables does not influence the risk of recurrence of colorectal adenomas Background and aim Impaired vasodilatation has been suggested to be caused by inhibition of nitric oxide generation by the recently described asymmetric dimethylarginine ( ADMA ) . In the present study we wanted to explore whether n-3 polyunsaturated fatty acid ( PUFA ) supplementation and /or diet intervention have beneficial influence on endothelial function assessed as plasma levels of ADMA and L-arginine . Methods A male population ( n = 563 , age 70 ± 6 yrs ) with long-st and ing hyperlipidemia , characterized as high risk individuals in 1970–72 , was included , r and omly allocated to receive placebo n-3 PUFA capsules ( corn oil ) and no dietary advice ( control group ) , dietary advice ( Mediterranean type ) , n-3 PUFA capsules , or dietary advice and n-3 PUFA combined and followed for 3 years . Fasting blood sample s were drawn at baseline and the end of the study . Results Compliance with both intervention regimens were demonstrated by changes in serum fatty acids and by recordings from a food frequency question naire . No influence of either regimens on ADMA levels were obtained . However , n-3 PUFA supplementation was accompanied by a significant increase in L-arginine levels , different from the decrease observed in the placebo group ( p < 0.05 ) . In individuals with low body mass index ( < 26 kg/m2 ) , the decrease in L-arginine on placebo was strengthened ( p = 0.01 ) , and the L-arginine/ADMA ratio was also significantly reduced ( p = 0.04 ) . Conclusion In this rather large r and omized intervention study , ADMA levels were not influenced by n-3 PUFA supplementation or dietary counselling . n-3 PUFA did , however , counteract the age-related reduction in L-arginine seen on placebo , especially in lean individuals , which might be discussed as an improvement of endothelial function 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 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 Serum lipoprotein[a ] ( Lp[a ] ) is a strong risk factor for coronary heart disease . We therefore examined the effect of dietary fatty acid composition on serum Lp[a ] levels in three strictly controlled experiments with healthy normocholesterolemic men and women . In Expt . I , 58 subjects consumed a control diet high in saturated fatty acids for 17 days . For the next 36 days , 6.5 % of total energy intake from saturated fatty acids was replaced by monounsaturates plus polyunsaturates ( monounsaturated fatty acid diet ; n = 29 ) or by polyunsaturates alone ( polyunsaturated fatty acid diet ; n = 29 ) . Both diets caused a slight , nonsignificant , increase in median Lp[a ] levels , with no difference between diets . In Expt . II , 10 % of energy from the cholesterol-raising saturated fatty acids ( lauric , myristic , and palmitic acid ) was replaced by oleic acid or by trans-monounsaturated fatty acids . Each of the 59 participants received each diet for 3 weeks in r and om order . The median level of Lp[a ] was 26 mg/l on the saturated fatty acid diet ; it increased to 32 mg/l ( P less than 0.020 ) on the oleic acid diet and to 45 mg/l ( P less than 0.001 ) on the trans-fatty acid diet . The difference in Lp[a ] between the trans-fatty acid and the oleic acid diets was also highly significant ( P less than 0.001 ) . Expt . III involved 56 subjects ; all received 8 % of energy from stearic acid , from linoleic acid , or from trans-monounsaturates , for 3 weeks each . All other nutrients were equal . ( ABSTRACT TRUNCATED AT 250 WORDS 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 The effect of fatty fish consumption on plasma lipid and lipoprotein concentrations was studied in 118 healthy men in a cross-over controlled trial . Subjects ate 100 g or more of fatty fish at least twice a week for 3 months , and little or no fatty fish for another 3 months . The mean plasma triglyceride concentration decreased significantly by 6.7 % on the fish diet ; there were no significant changes in plasma total cholesterol , high-density lipoprotein cholesterol , or low-density lipoprotein cholesterol . A realistic intake of fatty fish has a detectable effect on blood lipids 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 The Polyp Prevention Trial ( PPT ) was a multicenter r and omized clinical trial design ed to determine the effects of a high-fiber ( 4.30 g/MJ ) , high-fruit- and -vegetable ( 0.84 servings/MJ ) , low-fat ( 20 % of energy from fat ) diet on the recurrence of adenomatous polyps in the large bowel . OBJECTIVE Our goal was to determine whether the PPT intervention plan could effect change in 3 dietary goals and to examine the intervention 's effect on the intake of other food groups and nutrients . DESIGN Participants with large-bowel adenomatous polyps diagnosed in the past 6 mo were r and omly assigned to either the intervention ( n = 1037 ) or the control ( n = 1042 ) group and remained in the trial for 4 y. Three dietary assessment instruments were used to measure dietary change : food-frequency question naires ( in 100 % of the sample ) , 4-d food records ( in a 20 % r and om cohort ) , and 24-h dietary recalls ( in a 10 % r and om sample ) . RESULTS Intervention participants made and sustained significant changes in all PPT goals as measured by the dietary assessment instruments ; the control participants ' intakes remained essentially the same throughout the trial . The absolute differences between the intervention and control groups over the 4-y period were 9.7 % of energy from fat ( 95 % CI : 9.0 % , 10.3 % ) , 1.65 g dietary fiber/MJ ( 95 % CI : 1.53 , 1.74 ) , and 0.27 servings of fruit and vegetables/MJ ( 95 % CI : 0.25 , 0.29 ) . Intervention participants also reported significant changes in the intake of other nutrients and food groups . The intervention group also had significantly higher serum carotenoid concentrations and lower body weights than did the control group . CONCLUSION Motivated , free-living individuals , given appropriate support , can make and sustain major dietary changes over a 4-y period BACKGROUND Elevated plasma total homocysteine ( tHcy ) concentrations are associated with increased risk of vascular disease , and there is a strong inverse association between dietary and blood folate and blood tHcy concentrations . Increased folate consumption may lower the risk of tHcy-mediated cardiovascular disease . OBJECTIVES The objective was to determine the most appropriate means of increasing dietary folate to reduce plasma tHcy . DESIGN Sixty-five free-living subjects aged 36 - 71 y with tHcy concentrations > /=9 micromol/L participated in a r and omized , controlled trial to compare 3 approaches for increasing dietary folate to approximately 600 microg/d : folic acid supplementation , consumption of folic acid-fortified breakfast cereals , and increased consumption of folate-rich foods . RESULTS An intake of 437 microg folic acid/d from supplements result ed in a 27-nmol/L increase in serum folate and a 21 % reduction in tHcy , relative to the change in a control group . In subjects who consumed folic acid-fortified breakfast cereal , folate intake increased by an average of 298 microg , serum folate increased by 21 nmol/L , and tHcy concentrations decreased by 24 % . Increased intakes of folate-rich foods result ed in a 418-microg increase in dietary folate , a 7-nmol/L increase in serum folate , and a 9 % reduction in tHcy concentrations . The decrease in tHcy was negatively correlated ( r = -0.66 ) with the increase in serum folate . CONCLUSIONS Daily consumption of folic acid-fortified breakfast cereals and the use of folic acid supplements appear to be the most effective means of reducing tHcy concentrations . The reduction in tHcy was significantly negatively correlated with the increase in serum folate , which may be a useful marker for measuring dietary change OBJECTIVE To examine stage-matched nutrition counseling by family physicians and its effect on dietary intake , anthropometry , and serum lipid levels in patients at elevated risk for cardiovascular disease . METHODS In this controlled trial , patients r and omized to intervention practice s received nutrition information following the Stages-of-Change Model , and patients r and omized to control practice s received usual care . RESULTS At both 6 and 12 months after baseline , total fat intake and saturated fat intake declined significantly more in the intervention group than in the control group : -5.7 % and -2.6 % of energy , respectively , at 6 months , and -3.6 % and -1.7 % of energy , respectively , at 12 months . For energy intake , body weight , and BMI , there were significant differences between groups only at 6 months : -0.8 megajoules ( MJ ) , -0.7 kg , and -0.3 kg/m(2 ) , respectively . None of the serum lipid values changed significantly between groups at 12 months . CONCLUSIONS Nutritional counseling based on stages of change led to reductions in dietary fat intake and weight loss in the short term . However , we found no corresponding changes in serum lipid concentrations 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 BACKGROUND Few trials have evaluated the effects of reduced sodium intake in older individuals , and no trial has examined the effects in relevant subgroups such as African Americans . PATIENTS AND METHODS The effects of sodium reduction on blood pressure ( BP ) and hypertension control were evaluated in 681 patients with hypertension , aged 60 to 80 years , r and omly assigned to a reduced sodium intervention or control group . Participants ( 47 % women , 23 % African Americans ) had systolic BP less than 145 mm Hg and diastolic BP less than 85 mm Hg while taking 1 antihypertensive medication . Three months after the start of intervention , medication was withdrawn . The primary end point was occurrence of an average systolic BP of 150 mm Hg or more , an average diastolic BP of 90 mm Hg or more , the resumption of medication , or a cardiovascular event during follow-up ( mean , 27.8 months ) . RESULTS Compared with control , mean urinary sodium excretion was 40 mmol/d less in the reduced sodium intervention group ( P<.001 ) ; significant reductions in sodium excretion occurred in subgroups defined by sex , race , age , and obesity . Prior to medication withdrawal , mean reductions in systolic and diastolic BPs from the reduced sodium intervention , net of control , were 4.3 mm Hg ( P<.001 ) and 2.0 mm Hg ( P = .001 ) . During follow-up , an end point occurred in 59 % of reduced sodium and 73 % of control group participants ( relative hazard ratio = 0.68 , P<.001 ) . In African Americans , the corresponding relative hazard ratio was 0.56 ( P = .005 ) ; results were similar in other subgroups . In dose-response analyses , end points were progressively less frequent with greater sodium reduction ( P for trend = .002 ) . CONCLUSION A reduced sodium intake is a broadly effective , nonpharmacologic therapy that can lower BP and control hypertension in older individuals OBJECTIVE --To evaluate the long term efficacy of diets in lowering serum cholesterol concentration . DESIGN --Descriptive overview of 16 published controlled trials of six months ' duration or longer . SETTING --Trials had been conducted in hospital clinics ( 6 ) , industry ( 3 ) , mental hospitals or institutions ( 3 ) , and in general population s ( 4 ) . PATIENTS --Trials had been conducted in high risk subjects ( 5 ) , in unselected healthy subjects ( 6 ) , or for secondary prevention in patients with coronary heart disease ( 5 ) . Women were included in only four trials . INTERVENTIONS --Diets equivalent to the step 1 diet were employed in eight trials , with individual intervention by dietitians ( 3 ) or occupational physicians ( 2 ) or with population advice ( 3 ) . Intensive diets which were more rigorous than the step 2 diet were employed in eight trials . MAIN OUTCOME MEASURES --Net change in serum total cholesterol concentration in subjects receiving treatment with diet compared with values in control subjects after six months to 10 years . RESULTS --In five trials with the step 1 diet as individual intervention the net reduction in serum cholesterol concentration ranged from 0 % to 4.0 % over six months to six years . In trials with population education reductions in cholesterol concentrations were 0.6 - 2.0 % over five to 10 years . When population and individual dietary advice were combined changes in cholesterol concentration ranged from a fall of 2.1 % to a rise of 1.0 % over four to 10 years . Diets more intensive than the step 2 diet reduced serum cholesterol concentration by 13 % over five years in selected high risk men in the population ; by 6.5 - 15.1 % over two to five years in hospital out patients ; and by 12.8 - 15.5 % over one to four and a half years in patients in institutions . CONCLUSIONS --The response to a step 1 diet is too small to have any value in the clinical management of adults with serum cholesterol concentrations above 6.5 mmol/l . Current guidelines recommend screening of serum cholesterol concentration in healthy subjects , followed by treatment with a step 1 diet . The guidelines should be review ed to provide a more realistic estimate of the effect of a step 1 diet and of the likely need for lipid lowering drugs Background In Africa hypertension is common and stroke is increasing . Detection , treatment and control of high blood pressure ( BP ) is limited . BP can be lowered by reducing salt intake . In Africa salt is added to the food by the consumer , as processed food is rare . A population -wide approach with programmes based on health education and promotion is thus possible . Methods We carried out a community-based cluster r and omised trial of health promotion in 1,013 participants from 12 villages ( 628 women , 481 rural dwellers ) ; mean age 55 years to reduce salt intake and BP . Average BP was 125/74 mmHg and urinary sodium ( UNa ) 101 mmol/day . A health promotion intervention was provided over 6 months to all villages . Assessment s were made at 3 and 6 months . Primary end-points were urinary sodium excretion and BP levels . Results There was a significant positive relationship between salt intake and both systolic ( 2.17 mmHg [ 95 % CI 0.44 to 3.91 ] per 50 mmol of UNa per day , p < 0.001 ) and diastolic BP ( 1.10 mmHg [ 0.08 to 1.94 ] , p < 0.001 ) at baseline . At six months the intervention group showed a reduction in systolic ( 2.54 mmHg [ -1.45 to 6.54 ] ) and diastolic ( 3.95 mmHg [ 0.78 to 7.11 ] , p = 0.015 ) BP when compared to control . There was no significant change in UNa . Smaller villages showed greater reductions in UNa than larger villages ( p = 0.042 ) . Irrespective of r and omisation , there was a consistent and significant relationship between change in UNa and change in systolic BP , when adjusted for confounders . A difference in 24-hour UNa of 50 mmol was associated with a lower systolic BP of 2.12 mmHg ( 1.03 to 3.21 ) at 3 months and 1.34 mmHg ( 0.08 to 2.60 ) at 6 months ( both p < 0.001 ) . Conclusion In West Africa the lower the salt intake , the lower the BP . It would appear that a reduction in the average salt intake in the whole community may lead to a small but significant reduction in population systolic BP BACKGROUND Dietary behavior , specifically a low-fat , high-fiber diet , plays a role in the primary prevention of chronic diseases including cancer . DESIGN A community-based r and omized trial to assess the impact of a low-intensity , physician-endorsed , self-help dietary intervention that provided tailored dietary feedback , and was design ed to promote improved fat and fiber behavior in a rural , low-education/low-literacy , partly minority population . The data were collected from 1999 to 2003 . SETTING / PARTICIPANTS A total of 754 patients from three physician practice s in rural Virginia completed a baseline telephone survey assessing dietary and psychosocial information , and were then r and omly assigned to the intervention or control condition . Follow-up telephone evaluation was based on 522 participants at 1 month , 470 at 6 months , and 516 participants at 12 months . INTERVENTION A series of tailored feedback , followed by brief telephone counseling and theory-based nutritional education booklets , provided by staggered delivery to the home . MAIN OUTCOME MEASURES Dietary fat and fiber behavior , dietary intentions to change , self-efficacy for dietary change , and fat and fiber knowledge . RESULTS The intervention group demonstrated significant improvement in dietary fat and fiber behaviors and intentions to change fat and fiber intake ( p < 0.05 ) at 1 , 6 , and 12 months . CONCLUSIONS The Rural Physician Cancer Prevention Project provides an effective model for achieving public health-level dietary health behavior changes among a rural , minority , and low-literacy/low-education population 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 OBJECTIVES This National Cancer Institute-funded study sought to increase fruit and vegetable consumption among women served by the WIC program in Maryl and . METHODS Over a 2-year period , a multifaceted intervention program using a r and omized crossover design sought to increase fruit and vegetable consumption at 16 WIC program sites in Baltimore City and 6 Maryl and counties . Participants were surveyed at baseline , 2 months postintervention , and 1 year later . RESULTS Two months postintervention , mean daily consumption had increased by 0.56 + /- 0.11 servings in intervention participants and 0.13 + /- 0.07 servings in control participants ( P = .002 ) . Intervention participants also showed greater changes in stages of change , knowledge , attitudes , and self-efficacy . Changes in consumption were closely related to number of nutrition sessions attended , baseline stage of change , race , and education . One year later , mean consumption had increased by an additional 0.27 servings in both intervention and control participants . CONCLUSIONS Dietary changes to prevent cancer can be achieved and sustained in this hard-to-reach , low-income population . However , many obstacles must be overcome to achieve such changes BACKGROUND A diet low in saturated fat and cholesterol is the st and ard initial treatment for hypercholesterolemia . However , little quantitative information is available about the efficacy of dietary therapy in clinical practice or about the combined effects of diet and drug therapy . METHODS One hundred eleven out patients with moderate hypercholesterolemia were treated at five lipid clinics with the National Cholesterol Education Program Step 2 diet ( which is low in fat and cholesterol ) and lovastatin ( 20 mg once daily ) , both alone and together . A diet high in fat and cholesterol and a placebo identical in appearance to the lovastatin were used as the respective controls . Each of the 97 patients completing the study ( 58 men and 39 women ) underwent four consecutive nine-week periods of treatment according to a r and omized , balanced design : a high-fat diet-placebo period , a low-fat diet-placebo period , a high-fat diet-lovastatin period , and a low-fat diet-lovastatin period . RESULTS The level of low-density lipoprotein ( LDL ) cholesterol was a mean of 5 percent ( 95 percent confidence interval , 3 to 7 percent ) lower during the low-fat diet than during the high-fat diet ( P < 0.001 ) . With lovastatin therapy as compared with placebo , the reduction was 27 percent . Together , the low-fat diet and lovastatin led to a mean reduction of 32 percent in the level of LDL cholesterol . The level of high-density lipoprotein ( HDL ) cholesterol fell by 6 percent ( 95 percent confidence interval , 4 to 8 percent ) during the low-fat diet ( P < 0.001 ) and rose by 4 percent during treatment with lovastatin ( P < 0.001 ) . The ratio of LDL to HDL cholesterol and the level of total triglycerides were reduced by lovastatin ( P < 0.001 ) , but not by the low-fat diet . CONCLUSIONS The effects of the low-fat-low-cholesterol diet and lovastatin on lipoprotein levels were independent and additive . However , the reduction in LDL cholesterol produced by the diet was small , and its benefit was possibly offset by the accompanying reduction in the level of HDL cholesterol AIMS To study the long-term ( 1- and 2-year ) effect of a lifestyle intervention on non-diabetic first-degree relatives of type 2 diabetic patients , i.e. , the 1-year effect of diet versus diet and exercise in relation to a control group and the 2-year sustainability of these treatment effects . METHOD Seventy-seven healthy first-degree relatives ( men and women ) between the ages of 25 and 55 were allocated to one of three groups : diet group ( D ) , diet and exercise group ( DE ) and control group ( C ) . For ethical reasons , after 1 year the control group began the intervention and were followed for another 2 years . Diet and physical activity counselling was based on current nutrition recommendations , including increased intake of fatty fish and low glycaemic index foods . The fatty acid composition of the erythrocyte membrane was studied as an objective measure of dietary change . Assessment s included fasting insulin , 2-h insulin , oral glucose tolerance test ( OGTT ) , anthropometry and blood lipid measurements . Groups D and DE received intensive follow-up through unannounced telephone interviews during the first 4 months . RESULTS Dietary changes were significant at 1 year , and to a large degree sustained at 2 years . Adherence to advice regarding fat quality was confirmed through changes in the fatty acid composition of the erythrocyte membrane . The least active subjects in DE increased their physical activity ( PA ) . At 1 year , group D showed a reduction in the ratio of LDL to HDL cholesterol ( p=0.028 ) while group DE decreased their body weight by 2.7 % ( p<0.029 ) and increased HDL ( p<0.037 ) versus controls . At 2 years , cholesterol levels ( total , LDL and the ratio LDL/HDL ) were reduced within group D and when compared to DE ( p=0.022 , 0.009 , 0.035 , respectively ) . Fasting insulin was reduced within group DE and when compared to group D ( p=0.025 ) . CONCLUSIONS Positive changes in lifestyle , blood lipids and fasting insulin can be achieved and maintained in a non-diabetic population at risk of type 2 diabetes after 2 years 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 This field experiment examined the impact of an individual 's need for cognition ( NFC ; the tendency to enjoy thinking deeply about issues ) , complex versus simple messages , and the interaction of NFC and message type on encouraging fruit and vegetable consumption . Callers to the Cancer Information Service of the National Cancer Institute ( N = 517 ) were asked to participate in the experiment at the end of their call . Individual NFC was assessed , and participants were assigned r and omly to receive a telephone message promoting fruit and vegetable consumption that was either complex and multifaceted or simple and straightforward . Similarly constructed brochures were mailed immediately following the call , and additional brochures were mailed 2 and 3 months later . Although NFC did not predict intake , complex messages were more effective than simple messages in motivating fruit and vegetable consumption 1 and 4 months later 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 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 28 patients who had a sustained diastolic blood pressure of 95 to 104 mm Hg and who had no treatment for it for at least 13 months before the trial , but who were otherwise unselected , took part in a r and omised controlled trial in which the effect of a restricted sodium diet was compared with that of a general health package . The general health package did not include any specific hypotensive procedures . Changes in blood pressure were measured at predetermined intervals over the course of a year . Within each group both systolic and diastolic blood pressure fell to a highly significant extent after a year , but there was no significant difference between the groups . It would thus seem that the antihypertensive effect of a restricted sodium diet may be related to the increased consultation and monitoring activity of such intervention rather than to the dietary manipulation itself Abstract Objective To examine whether adherence to the modified Mediterranean diet , in which unsaturates were substituted for monounsaturates , is associated with longer life expectancy among elderly Europeans . Design Multicentre , prospect i ve cohort study . Setting Nine European countries ( Denmark , France , Germany , Greece , Italy , the Netherl and s , Spain , Sweden , United Kingdom ) . Participants 74 607 men and women , aged 60 or more , without coronary heart disease , stroke , or cancer at enrolment and with complete information about dietary intake and potentially confounding variables . Main outcome measures Extent of adherence to a modified Mediterranean diet using a scoring system on a 10 point scale , and death from any cause by time of occurrence , modelled through Cox regression . Results An increase in the modified Mediterranean diet score was associated with lower overall mortality , a two unit increment corresponding to a statistically significant reduction of 8 % ( 95 % confidence interval 3 % to 12 % ) . No statistically significant evidence of heterogeneity was found among countries in the association of the score with overall mortality even though the association was stronger in Greece and Spain . When dietary exposures were calibrated across countries , the reduction in mortality was 7 % ( 1 % to 12 % ) . Conclusion The Mediterranean diet , modified so as to apply across Europe , was associated with increased survival among older people BACKGROUND High dietary intakes of fruit and vegetables are associated with reduced risks of cancer and cardiovascular disease . Short-term intensive dietary interventions in selected population s increase fruit and vegetable intake , raise plasma antioxidant concentrations , and lower blood pressure , but long-term effects of interventions in the general population are not certain . We assessed the effect of an intervention to increase fruit and vegetable consumption on plasma concentrations of antioxidant vitamins , daily fruit and vegetable intake , and blood pressure . METHODS We undertook a 6-month , r and omised , controlled trial of a brief negotiation method to encourage an increase in consumption of fruit and vegetables to at least five daily portions . We included 690 healthy participants aged 25 - 64 years recruited from a primary -care health centre . FINDINGS Plasma concentrations of alpha-carotene , beta-carotene , lutein , beta-cryptoxanthin , and ascorbic acid increased by more in the intervention group than in controls ( significance of between-group differences ranged from p=0.032 to 0.0002 ) . Groups did not differ for changes in lycopene , retinol , alpha-tocopherol , gamma-tocopherol , or total cholesterol concentrations . Self-reported fruit and vegetable intake increased by a mean 1.4 ( SD 1.7 ) portions in the intervention group and by 0.1 ( 1.3 ) portion in the control group ( between-group difference=1.4 , 95 % CI 1.2 - 1.6 ; p<0.0001 ) . Systolic blood pressure fell more in the intervention group than in controls ( difference=4.0 mm Hg , 2.0 - 6.0 ; p<0.0001 ) , as did diastolic blood pressure ( 1.5 mm Hg , 0.2 - 2.7 ; p=0.02 ) . INTERPRETATION The effects of the intervention on fruit and vegetable consumption , plasma antioxidants , and blood pressure would be expected to reduce cardiovascular disease in the general population The Polyp Prevention Trial ( PPT ) is a multicenter r and omized controlled trial examining the effect of a low-fat ( 20 % of total energy intake ) , high-fiber ( 18 g/1000 kcal ) , high-vegetable and -fruit ( 5 - 8 daily servings ) dietary pattern on the recurrence of adenomatous polyps of the large bowel , precursors of most colorectal malignancies . Eligibility criteria include one or more adenomas removed within 6 months of r and omization ; complete nonsurgical polyp removal and complete colonic examination to the cecum at the qualifying colonoscopy : age 35 years of more ; no history of colorectal cancer , inflammatory bowel disease , or large bowel resection ; and satisfactory completion of a food frequency question naire and 4-day food record . Of approximately 38,277 potential participants with one or more polyps recently resected , investigators at eight clinical centers r and omized 2,079 ( 5.4 % ; 1,037 in the intervention and 1,042 in the control arm ) between June 1991 and January 1994 , making the PPT the largest adenoma recurrence trial ever conducted . Of PPT participants , 35 % are women and 10 % are minorities . At study entry , participants averaged 61.4 years of age ; 14 % of them smoked , and 22 % used aspirin . At the baseline colonoscopy , 35 % of participants had two or more adenomas , and 29 % had at least one large ( > of = 1 cm ) adenoma . Demographic , behavioral , dietary , and clinical characteristics are comparable across the two study arms . Participants have repeat colonoscopies after 1 ( T(1 ) ) and 4 ( T(4 ) ) years of follow-up . The primary end point is adenoma recurrence ; secondary end points include number , size , location , and histology of adenomas . All resected lesions are review ed central ly by gastrointestinal pathologists . The trial provides 90 % power to detect a reduction of 24 % in the annual adenoma recurrence rate . The primary analytic period , on which sample size calculations were based is 3 years ( T(1 ) to T(4 ) ) , which permits a 1-year lag time for the intervention to work and allows a more definitive clearing of lesions at T(1 ) , given that at least 10 - 15 % of polyps may be missed at baseline . The final ( T(4 ) ) colonoscopies are expected to be completed in early 1998 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 This r and omized clinical trial examined the feasibility of low-fat dietary interventions among postmenopausal women of diverse background s. During 1992 - 1994 , 2,208 women aged 50 - 79 years , 28 % of whom were black and 16 % Hispanic , enrolled at clinics in Atlanta , Georgia , Birmingham , Alabama , and Miami , Florida . Intervention/support groups met periodically with a nutritionist to reduce fat intake to 20 % of energy and to make other diet modifications . At 6 months postr and omization , the intervention group reduced fat intake from 39.7 % of energy at baseline to 26.4 % , a reduction of 13.3 % of energy , compared with 2.3 % among controls . Saturated fatty acid and cholesterol intakes were reduced , but intakes of fruits and vegetables , but not grain products , increased . Similar effects were observed at 12 and 18 months . Black and non-Hispanic white women had similar levels of reduction in fat , but the decrease in Hispanic women was less . Changes did not vary significantly by education . While bias in self-reported intakes may have result ed in somewhat overestimated changes in fat intake , the reported reduction was similar to the approximately 10 % of energy decrease found in most trials and suggests that large changes in fat consumption can be attained in diverse study population s and in many subgroups Diet is an important factor in the causation of cancer . Previous systematic review s of one-to-one interventions to encourage dietary change have found that such interventions can achieve modest improvements in diet . However , such interventions are re source intensive and unlikely to be good value for money at a population level . Interventions that address groups , communities or whole population s may be less re source intensive and effect change in a wider population . We report a systematic review of such interventions . We set wide inclusion criteria , including before- and -after studies and studies with a non-r and omized comparison group as well as r and omized trials . We found eighteen studies based in the community , seventeen based on worksites , five based in churches and one based in a supermarket . Interventions which targeted fruit and vegetable intake were most likely to be successful , particularly in worksites and churches . There was also evidence of small positive effects on reducing fat intake in worksites and churches . Overall the community-based interventions showed little effect . The studies included in the present review were generally poorly reported . Dietary changes are reported in the relatively short-term studies review ed here but may not be sustained in the long term . The effects that we have identified are small but the reach is potentially very wide , in some cases as wide as a whole country . The cost effectiveness of such strategies remains to be evaluated Based on reports that fruits and vegetables may protect against breast cancer , this r and omized intervention study tested the feasibility of increasing fruit and vegetable intake among healthy women to 9 daily servings through individual dietary counseling and group activities . Adherence to the dietary recommendations was monitored by 24-h food recalls , log sheets , and plasma carotenoid assessment s. To explore possible cancer protective mechanisms of fruits and vegetables , we investigated the treatment effect on plasma phenol levels and on thiobarbituric acid-reactive substances measured as malondialdehyde equivalents , a possible marker of oxidative damage . At baseline , women in the intervention ( n = 13 ) and control ( n = 16 ) group reported an average daily consumption of 3.3 and 3.2 fruit and vegetable servings , respectively . After 3 and 6 months of intervention , intake in the intervention group had increased to 8.3 and 7.4 servings , whereas the control group reported an average of 4.2 and 4.1 daily servings . An increase of plasma carotenoid levels from 1249 microg/liter at baseline to 1854 and 1827 microg/liter after 3 and 6 months confirmed compliance with the dietary recommendations in the intervention group . Plasma carotenoid levels among controls changed slightly from 1165 to 1231 and 1291 microg/liter Whereas total phenol levels did not respond according to our hypothesis , malondialdehyde levels decreased slightly in the intervention group . These results suggest that motivated women can substantially increase their fruit and vegetable intake , which leads to a notable increase in plasma carotenoid levels Abstract : This study examined whether subjects who participated in a 12-mo intervention would maintain their diets 1 yr after the study ended and whether the diets of household members were affected . Premenopausal women , who had at least one first-degree relative with breast cancer ( n = 122 ) , were r and omized to one of four diets : control , low fat ( 15 % of energy ) , high fruit and vegetable ( FV , nine servings per day ) , and combination low fat , high FV . Study subjects and one household member were asked to complete the Block ‘ 95 food-frequency question naire ( FFQ ) at baseline , 1 yr , and 2 yr . Study subjects also completed 24-h recalls and 4-day food records at baseline and Year 1 . Fat and FV intakes by all three assessment methods compared reasonably well except that fat intakes by FFQ were somewhat higher . FV intakes by FFQ in the high-FV and combination arms increased significantly from 4 servings per day to about 10 servings per day at Year 1 and 7 servings per day at Year 2 . FV intakes increased much more modestly in the low-fat and control arms . Fat intakes in the low-fat and combination arms were lower at Year 1 than Year 2 , but mean Year 2 fat intakes of 26–28 % were still significantly lower than those at baseline . In household members , the only significant change was a small decrease in energy from fat at Year 1 in the household members of subjects who were in the combination arm . These results indicate that study subjects were making large dietary changes independently of their household members and that fat and FV intakes in study subjects 1 yr after intervention stopped were still substantially different from intakes at baseline 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 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 Male employees from four local worksites were recruited to participate in a short-term and low-intensity nutrition intervention which focused on promoting low-fat dietary habits . The sites were r and omized to control conditions or to the intervention programme that consisted of an individualized health risk appraisal , group sessions , mass media activities and environmental changes . Participants were seen before and three months after intervention to measure blood lipids , nutrition knowledge and dietary changes . Eighty-three per cent of all eligible subjects were screened ( n = 770 ) and follow-up measures were obtained for 82 % . The score for nutrition knowledge improved significantly in the intervention group . There was also a net reduction in the intake of total calories and in the percentage of energy from total fat . Reported intake of carbohydrates and proteins increased . For all employees assessed , there were no changes in mean total cholesterol level or fatty acid composition . Only among participants with hypercholesterolemia was a significant reduction in blood cholesterol observed . This low-intensity intervention programme achieved some self-reported dietary changes and was successful ( at least in part because statistical regression needs to be considered ) in obtaining a more short-term beneficial cholesterol level in employees at higher cardiovascular risk BACKGROUND Reducing dietary fat has been identified as a potential means of preventing chronic disease . Several studies have identified methods of changing dietary fat consumption in small , intensive intervention setting s. Fewer studies have examined how to improve dietary habits of individuals in the general public . METHODS The Eating for a Healthy Life ( EHL ) project was a r and omized trial [ n = 40 religious organizations ( ROs ) and 2175 individuals , 1099 in intervention ] . The study tested an intervention package of self-help books , motivational messages , and social interactions design ed to change dietary behaviors ( lowering fat , increasing fruit and vegetable consumption ) among members of religious organizations aged 18 and over . The primary outcomes are fat- and fruit- or vegetable-related behaviors measured using the Fat and Fiber Behavior ( FFB ) Question naire . RESULTS Religious organizations and their members participated fully in the initial study activities . CONCLUSIONS This study will support a rigorous test of the intervention package OBJECTIVES To investigate the effectiveness of a non-structured 15-min educational intervention by general practitioners ( GPs ) on modifications of daily diet among healthy adults . DESIGN Two arms r and omized trial lasting 12 months . SETTING Italian general practitioner wards . Subjects A total of 3,186 men and women aged 18 - 65 years recruited in the medical ward by their GPs . INTERVENTIONS An educational intervention and a brochure on the basics of a healthy diet based on the Italian Guidelines for a Correct Nutrition , 1998 . The main study goal was to attain an intake of fruits and vegetables > 5 servings per day . Follow-up visit every 6 months . Main outcome measures Weight , blood pressure , and a 40-items Food Frequency Question naire . RESULTS The intervention group showed a slightly reduced net intake of meat and a slightly increased net intake of fruits and vegetables , fish products , and olive oil . Body mass index ( BMI ) changed only in the treatment arm [ -0.41 95 % confidence interval ( 95 % CI ) -0.11 to -0.53 ] . The net change at 1 year in the intervention arm was + 1.31 ( CI 0.90 - 4.39 ) for fruits and vegetables , and -0.22 ( -0.11 to -0.69 ) for meat ( portions per week ) . We also computed a ' healthy diet score ' reflecting compliance with recommended dietary habits . In the intervention group , the mean score at recruitment was significantly lower than the mean score at the end of follow-up ( Crude score change = 0.29 ; CI 0.19 - 0.48 ) . No differences were observed in the control group ( Crude score change = -0.04 ; CI -0.22 - 0.02 ) . The difference in score from baseline to the final visit , comparing the intervention vs the control group , was statistically significant ( P < 0.001 ) ( MANOVA adjusted by sex , BMI , education , and time ) . CONCLUSIONS A brief educational intervention by GPs can induce multiple diet changes that may lower BMI and potentially reduce chronic disease risk in generally healthy adults OBJECTIVE This study evaluated the Michigan Farmers ' Market Nutrition Program in one Michigan county to determine its effect on fruit and vegetable consumption behavior . SUBJECTS/ SETTING Subjects were selected from WIC and Community Action Agency population s : 564 low income women completed the pretest ; 455 completed the posttest . Attrition rate was 19.3 % . INTERVENTION Subjects were assigned to one of 4 interventions : education about the use , storage and nutritional value of fruits and vegetables , distribution of farmers ' market coupons , both education and coupons , or no intervention . DESIGN Education-only and coupon and education groups were r and omly assigned ; clinic appointment timing determined assignment to no-intervention and coupon-only groups . MAIN OUTCOME MEASURES A self-administered question naire before and after intervention measured attitudes about fruit and vegetable consumption and intake of fruits and vegetables . WIC records documented redemption of coupons . STATISTICAL ANALYSES Data analysis included 2-way multivariate analysis of covariance , univariate analysis of covariance , logistic regression , and covariance structure modeling . RESULTS Both the education interventions and the coupon interventions had positive effects . Coupons had a direct effect on increasing fruit and vegetable consumption behavior but no effect on attitudes . Education had a direct effect on attitudes and seemed to exert an effect on consumption behavior through attitudes . The maximum impact of the intervention was achieved through a combination of education and coupons . APPLICATIONS This study demonstrated that a low-income population may be more likely to increase its fruit and vegetable consumption behavior when incentives such as coupons improve affordability 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 Less than 50 % of US adults follow dietary recommendations . Despite these figures , little research has focused on improving adherence to a therapeutic eating plan . The research utilizing self-efficacy theory has shown promise for improving behavior change and treatment adherence . This study evaluated the efficacy of a telephone-delivered , self-efficacy based intervention design ed to improve adherence to a cholesterol-lowering diet among those self-reporting nonadherence . Sixty-five men and women diagnosed with hypercholesterolemia were r and omized to usual care or treatment , which consisted of six intervention sessions delivered every 2 weeks by telephone and focused on how to manage eating behavior in challenging situations . There were significant between group differences post intervention in the consumption of saturated fat ( P < .001 ) and cholesterol ( P = .040 ) with the intervention group improving their dietary adherence . Significant change ( P = .013 ) occurred over time in low-density lipoprotein-cholesterol ( LDL-C ) in the intervention group . No changes were observed in self-efficacy between groups , suggesting that self-efficacy was not a mediator of the improved adherence . The study 's findings confirm that the telephone is a useful tool to deliver adherence-enhancing interventions OBJECTIVE To examine whether diet intervention can promote increased vegetable and fruit intake , as reflected in increased plasma carotenoid and decreased plasma total homocysteine concentrations , in premenopausal women with cervical intraepithelial neoplasia , a precancerous condition . DESIGN R and omized controlled diet intervention study . SUBJECTS Fifty-three free-living premenopausal women who had been diagnosed with cervical intraepithelial neoplasia , were r and omly assigned to an intervention ( n = 27 ) or a control ( n = 26 ) group . INTERVENTION Individualized dietary counseling to increase vegetable and fruit intake . MAIN OUTCOME MEASURES Diet was assessed by food frequency question naire . Plasma carotenoids and total homocysteine were measured at enrollment and at 6 months follow up . ANALYSIS Associations between baseline plasma concentrations of carotenoids and homocysteine and influencing factors were examined with multiple regression analysis . Repeated measures analysis of variance was used to test for group by time effects in these plasma concentrations . Plasma carotenoids at baseline and 6 months in the study groups , and differences in homocysteine concentrations from baseline to 6 months , were compared with independent sample t tests . RESULTS Repeated measures analysis of variance showed significant group by time effects ( P<.01 ) in plasma carotenoid and homocysteine concentrations . In the intervention group , total plasma carotenoids increased by an average of 91 % , from 2.04+/-0.13 ( mean+/-st and ard error of the mean ) to 3.90+/-0.56 micromol/L and plasma total homocysteine was reduced by 11 % , from 9.01+/-0.40 to 8.10+/-0.44 micromol/L ( P<.003 ) . Neither changed significantly in the control group . APPLICATIONS Individualized dietary counseling can effectively promote increased vegetable and fruit intake in premenopausal women . This dietary pattern may reduce risk for cancer and other chronic diseases and also promote an improvement in folate status 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 OBJECTIVES This study reports on Eat for Life , a multicomponent intervention to increase fruit and vegetable consumption among African Americans that was delivered through Black churches . METHODS Fourteen churches were r and omly assigned to 3 treatment conditions : ( 1 ) comparison , ( 2 ) self-help intervention with 1 telephone cue call , and ( 3 ) self-help with 1 cue call and 3 counseling calls . The telephone counseling in group 3 was based on motivational interviewing . The primary outcome , assessed at baseline and 1-year follow-up , was fruit and vegetable intake as assessed by 3 food frequency question naires . RESULTS Change in fruit and vegetable intake was significantly greater in the motivational interviewing group than in the comparison and self-help groups . The net difference between the motivational interviewing and comparison groups was 1.38 , 1.03 , and 1.21 servings of fruits and vegetables per day for the 2-item , 7-item , and 36-item food frequency question naires , respectively . The net difference between the motivational interviewing and self-help groups was 1.14 , 1.10 , and 0.97 servings for the 2-item , 7-item , and 36-item food frequency question naires , respectively . CONCLUSIONS Motivational interviewing appears to be a promising strategy for modifying dietary behavior , and Black churches are an excellent setting to implement and evaluate health promotion programs BACKGROUND Results are reported from a large r and omized trial design ed to increase fruit and vegetable consumption among callers to the National Cancer Institute 's Cancer Information Service ( CIS ) ( n = 1,717 ) . METHODS CIS callers assigned to the intervention group ( n = 861 ) received a brief proactive educational intervention over the telephone at the end of usual service , with two follow-up mailouts . Key educational messages and print material derived from the NCI 5 A Day for Better Health program were provided to intervention participants . Participants were interviewed by telephone at 4 weeks ( n = 1,307 ) , 4 months ( n = 1,180 ) , and 12 months for follow-up ( n = 1,016 ) . RESULTS Results obtained from a single-item measure of fruit and vegetable consumption indicate a significant intervention effect of 0.88 servings per day at 4 weeks follow-up ( P < 0.001 ) , 0.63 servings per day at 4 months follow-up ( P < 0.001 ) , and 0.43 servings per day at 12 months follow-up ( P < 0.001 ) . Using a 7-item food frequency measure , an intervention effect of 0.63 servings per day was obtained at 4 weeks follow-up ( P < 0.001 ) , compared with 0.39 servings per day at 4 months follow-up ( P = 0.002 ) and 0.44 servings per day at 12 months follow-up ( P = 0.002 ) . A 24-h recall assessment included in the 4-month interviews also yielded a significant intervention effect of 0.67 servings per day ( P = 0.015 ) . The vast majority of callers ( 90 % ) endorsed the strategy of providing 5 A Day information proactively within the CIS . CONCLUSIONS This brief educational intervention was associated with higher levels of self-reported fruit and vegetable intake at both short- and long-term follow-up . Additional research is recommended to test this or a similar intervention in diverse population 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 PURPOSE Current guidelines of the National Cholesterol Education Program ( NCEP ) recommend initial dietary counseling by physicians for most patients with hypercholesterolemia ; referral to a registered dietitian and lipid-lowering drugs are recommended only for patients who remain hypercholesterolemic . We evaluated the incremental value of detailed nutritional counseling by dietitians when added to general nutritional advice provided by physicians . SUBJECTS AND METHODS Hypercholesterolemic patients detected during a cholesterol screening project were r and omly assigned to receive dietary counseling by a physician only ( 70 patients ) or by a physician and a registered dietitian ( 66 patients ) . Patients were observed for 1 year to determine compliance with NCEP guidelines . RESULTS At 3 months , the mean ( + /- SD ) decrease in the serum low-density lipoprotein ( LDL ) cholesterol level was 7 % + /- 11 % in the physician group and 12 % + /- 10 % in the dietitian group ( P < 0.004 ) . A decrease of 10 % or more in the LDL cholesterol level was seen in 25 patients ( 36 % ) in the physician group and 43 patients ( 65 % ) in the dietitian group ( P < 0.001 ) . Only 40 ( 29 % ) of the patients in both groups achieved their NCEP target goals at 3 months . The majority of these were low-risk patients with an LDL cholesterol target goal of 160 mg/dL. At 12 months , both groups lost about half of the beneficial effects on LDL cholesterol levels , and the difference between the two groups diminished . CONCLUSIONS The short-term reduction in LDL cholesterol level achieved after counseling by dietitians is superior to that achieved by physicians . However , long-term compliance remains inadequate . For patients at high risk , consideration should be given to a more aggressive dietary approach and possibly earlier introduction of lipid-lowering medications High vegetable and fruit ( V&F ) consumption has been associated with a lower risk of several cancers . However , little is known about the ability of individuals to increase their intakes markedly . In this 1-year r and omized , controlled diet intervention study of men and women with a recent history of adenomas , the intervention group ( n = 100 ) was asked to increase V&F intake to at least eight servings per day ; the control group ( n = 101 ) continued eating their usual diet . End-point measures included V&F intake assessed by 3-day diet records , plasma carotenoids , serum lipids , urinary sodium and potassium , and body weight . The intervention group increased their daily V&F intake an average of 5.5 servings over 1 year ; the control group had an average decrease of 0.5 servings per day ( P < 0.001 ) . Plasma total carotenoids , alpha-carotene , beta-carotene , beta-cryptoxanthin , and lutein/zeaxanthin were each statistically significantly elevated over baseline ( 11 - 54 % ) in the intervention group compared with the control group over the duration of follow-up ( P < 0.001 ) . Urinary potassium excretion was elevated 14 % over baseline in the intervention group compared with no change in the control group ( P < 0.001 ) . Modest decreases in the intervention but not the control group were observed for total and low-density lipoprotein cholesterol . Plasma lycopene , triglycerides , high-density lipoprotein cholesterol , body weight , and urinary sodium were not affected by the intervention . V&F intake was significantly increased in this motivated population at higher risk of colon cancer and maintained for at least 12 months , as assessed using diet records and an ensemble of biomarkers BACKGROUND Few studies compare the influence of different types of dietary interventions on the dietary practice s of Latinas in the short and long term . The present study examined the 1-year impact of two innovative behavior-change approaches to reduce dietary fat and increase fiber . DESIGN Three-group r and omized controlled trial : ( 1 ) personalized dietary counseling via lay heath advisors ( promotoras ) plus tailored print material s delivered via the mail , ( 2 ) tailored mailed print material s only , and ( 3 ) targeted mailed " off-the-shelf " material s. SETTING / PARTICIPANTS A total of 357 Latinas were r and omly assigned to the three aforementioned conditions . INTERVENTION Promotora and tailored print material s. MAIN OUTCOME MEASURES Fat intake ( total grams of fat and percent calories from dietary fat ) and number of grams of dietary fiber . RESULTS Earlier work reported that at immediate post-intervention the promotora group achieved significantly lower levels of total fat grams , and lower levels of energy intake , total saturated fat , total carbohydrates , glucose , and fructose than the targeted group . However , the present longitudinal analyses suggest that the effects achieved by the promotoras dissipated over the 12-month follow-up period while the effects of the tailored group concurrently improved . CONCLUSIONS The high interactivity ( i.e. , calls , visits ) of the promotora condition may have been the most salient reinforcer and may have led to further tailoring , making this type of intervention more effective than the comparison groups in the short term . Further research should explore whether booster sessions involving promotoras help to maintain the impact over time 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 To assess the effectiveness of a cholesterol-lowering intervention design ed to facilitate the management of hypercholesterolemia by primary care clinicians . DESIGN R and omized controlled trial , with r and omization of clinician-patient groups . SETTING Twenty-one community and rural health centers in North Carolina and Virginia . PARTICIPANTS Primary care clinicians ( n = 42 , 71 % physicians ) and the patients they enrolled with high cholesterol ( n = 372 ) . Twenty-two clinicians were r and omized to give the special intervention ( 184 patients ) and 20 to give usual care ( 188 patients ) . Two thirds of participating patients were women , 40 % were African American , and 11 % were Native American . INTERVENTION A 90-minute tutorial to train clinicians how to use a structured assessment and treatment program ( Food for Heart Program ) consisting of a brief dietary assessment and three 5- to 10-minute dietary counseling sessions given by the primary care clinician , referral to a local dietitian if the low-density lipoprotein cholesterol ( LDL-C ) remained elevated at 4-month follow-up , and a prompt for the clinician to consider lipid-lowering medication based on the LDL-C at 7-month follow-up . MAIN OUTCOME MEASURES Changes in total and LDL cholesterol at 4-month follow-up and averaged over a 1-year follow-up period ( 4- , 7- , and 12-month follow-up ) . RESULTS At 4-month follow-up , total cholesterol decreased 0.33 mmol/L ( 12.6 mg/dL ) in the intervention group and 0.21 mmol/L ( 8.3 mg/dL ) in the control group : the difference was 0.11 mmol/L ( 4.2 mg/dL ) ( 90 % confidence interval [ CI ] , -0.02 to 0.24 mmol/L [ -0.7 to 9.1 mg/dL ] ) . The average reduction during the 1-year follow-up period was 0.09 mmol/L ( 3.6 mg/dL ) greater in the intervention group ( 90 % CI , -0.01 to 0.19 mmol/L [ -0.3 to 7.5 mg/dL ] ) . Eight percent of intervention patients were taking lipid-lowering medication at follow-up visits compared with 15 % of control patients . In a subgroup analysis restricted to the 89 % of returnees who were not taking lipid-lowering medication , the reduction in total cholesterol at 4-month follow-up was 0.14 mmol/L ( 5.5 mg/dL ) greater in the intervention group ( 95 % CI , 0.01 to 0.28 mmol/L [ 0.3 to 10.7 mg/dL ] ) ; averaged over 1 year , it was 0.14 mmol/L ( 5.3 mg/dL ) greater ( 95 % CI , 0.03 to 0.24 mmol/L [ 1.2 to 9.4 mg/dL ] ) . Changes in LDL-C were similar . CONCLUSIONS Total cholesterol and LDL-C decreased more in the intervention group than in the control group . Overall , the difference in lipid reduction between groups was modest and of borderline statistical significance ; among participants who did not take lipid-lowering medication during follow-up , the difference in lipid reduction between groups was larger . We conclude that primary care clinicians can be trained to give a cholesterol-lowering intervention to low-income patients that results in modest , short-term reductions in total cholesterol and BACKGROUND Dietary intervention is one of the important fields in cancer and cardiovascular disease prevention . The Hiraka Dietary Intervention Study is a community-based r and omized cross-over trial design ed to develop an effective dietary modification tool and system in an area with high mortality of stomach cancer and stroke . METHODS The subjects were 550 healthy volunteers and were r and omized into two groups with tailored dietary education to decrease sodium intake and to increase vitamin C and carotene intakes either in the first year ( intervention group ) or in the second year ( control group ) . Dietary changes were assessed using a vali date d self-administered diet history question naire , fasting blood sample s , and 48-hour urine sample s , which were obtained before and after the one year period . RESULTS During the first year , changes differed significantly between the intervention and control group for both dietary sodium intake ( -384 and + 255 mg/day , intervention and control respectively , p < 0.001 ) and urinary sodium excretion ( -1003 and -84 mg/day , p < 0.001 ) . Although favorable net changes were also observed in dietary carotene ( + 418 and + 220 mug/day , p < 0.05 ) and vitamin C ( + 13 and + 2 mg/day , p < 0.05 ) , the serum level differences were modest ( + 13 and -25 mg/L , p = 0.09 for carotene , + 0.1 and -0.5 mg/L , p = 0.07 for ascorbic acid ) . CONCLUSION The present dietary intervention strategy effectively decreased sodium and increased carotene and vitamin C intakes , although the former was more distinct BACKGROUND Reducing the intakes of fats and increasing consumption of fruits and vegetables are an important goal for improving population health . Analyzing the effects of nutrition education programs on subjects ' dietary intakes incorporating factors such as habit persistence in diets , unhealthy eating habits , perceptions of health risks , participation motivation , and expectancies can yield useful insights . METHODS A Food Frequency Question naire ( FFQ ) was used to measure intakes at baseline , 6 and 12 months , by 318 and 548 postmenopausal women in , respectively , the Control and Intervention groups of the Women 's Health Trial : Feasibility Study in Minority Population s ( WHTFSMP ) . Information on background , behavioral , and anthropometric variables was collected . The Intervention group met in classes led by nutritionists . Dynamic r and om effects models were estimated for the two groups using the data at baseline , 6 and 12 months on the intakes of carbohydrate , saturated , monounsaturated , and polyunsaturated fats , fiber , beta-carotene , ascorbic acid , and calcium . RESULTS The nutrition education program lowered the intakes of fats while increasing fiber , beta-carotene , and ascorbic acid intakes especially in subjects scoring high on indices reflecting concerns about health , desirability of change , and participation motivation . In addition , subjects ' education was a predictor of dietary intakes in the Intervention group . CONCLUSIONS Nutrition education can be an effective tool for improving diets , but behavioral characteristics deserve greater attention in helping to design the most effective approaches for various target groups 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 OBJECTIVE This study assessed the effectiveness of a 4-month intervention using stage-based newsletters , computer-based communication , and motivational interviewing to increase fruit and vegetable consumption by college students aged 18 to 24 years . DESIGN Participants were stratified by stage of change for fruit and vegetable consumption and r and omized to an intervention or control group . Participants completed the staging algorithm for fruit and vegetable intake , which included a one-item food frequency question , a 26-item food frequency question naire ( FFQ ) , an 18-item decisional balance question naire , and a five-item self-efficacy question naire at baseline and completion of study . SUBJECTS A convenience sample of 437 college students enrolled in a rural , l and grant university was enrolled in the study . Only nondietetics majors between ages 18 to 24 years were included in the study . A total of 314 students finished the study for a completion rate of 72 % . INTERVENTION After baseline staging and r and omization , the intervention group participants received four stage-based newsletters , one motivational interview , and an individually tailored e-mail follow-up over a 4-month period . Control group participants only received assessment at baseline and at completion . MAIN OUTCOME MEASURES Two fruit and vegetable instruments , a one-item food frequency question , and a 26-item FFQ measured daily consumption of fruits and vegetables at baseline and postintervention . STATISTICAL ANALYSES PERFORMED The SAS system for Windows , version 8 ( 1999 , SAS Institute , Inc , Cary , NC ) , was used for analysis , including the following tests : PROC GLM , PROC FREQ , and PROC NPAR1WAY , Kruskal-Wallis , Fisher , Wilcoxon rank sum , and chi(2 ) . RESULTS Fruit and vegetable consumption increased significantly more for the intervention group than the control group . Consumption increased in the intervention group by one serving a day for both instruments compared with 0.4 servings a day in the control group for a one-item instrument and no change in the control group for a 26-item FFQ . CONCLUSIONS This intervention is an effective way to increase fruit and vegetable consumption by young adults OBJECTIVE To evaluate the effectiveness of computer-tailored newsletter interventions in improving the number and variety of fruits and vegetables eaten by adults . DESIGN The 4-group r and omized trial with pre- and postintervention measures consisted of a control group and 3 intervention groups receiving nontailored newsletters , computer-tailored newsletters , or tailored newsletters with tailored goal - setting information . Intervention groups received 1 newsletter each month for 4 months . SUBJECTS Baseline surveys were completed by 710 health maintenance organization clients . Postintervention surveys administered 6 months after baseline were completed by 573 participants ( 80.8 % ) . INTERVENTION All newsletters contained strategies for improving fruit and vegetable consumption . Tailored newsletters used computer algorithms to match a person 's baseline survey information with the most relevant newsletter messages for promoting dietary change . MAIN OUTCOME MEASURES Daily intake and weekly variety of fruits and vegetables were measured using a food frequency question naire . STATISTICAL ANALYSES PERFORMED Analysis of covariance and Tukey 's honestly significant difference test were used to assess differences in the number and variety of fruits and vegetables consumed among intervention groups . RESULTS For persons completing postintervention surveys ( n = 573 ) , all 3 newsletter groups had significantly higher daily intake and variety scores compared with the control group . Although there was a trend of improved intake and variety with each added newsletter element , there were no significant differences at follow-up among the newsletter groups . CONCLUSIONS Newsletters can be effective in improving the fruit and vegetable consumption of adults . In this study , a computer-tailoring system did not significantly enhance the effect of the nutrition newsletters on fruit and vegetable intake 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 The associations of diastolic blood pressure ( DBP ) with stroke and with coronary heart disease ( CHD ) were investigated in nine major prospect i ve observational studies : total 420,000 individuals , 843 strokes , and 4856 CHD events , 6 - 25 ( mean 10 ) years of follow-up . The combined results demonstrate positive , continuous , and apparently independent associations , with no significant heterogeneity of effect among different studies . Within the range of DBP studied ( about 70 - 110 mm Hg ) , there was no evidence of any " threshold " below which lower levels of DBP were not associated with lower risks of stroke and of CHD . Previous analyses have described the uncorrected associations of DBP measured just at " baseline " with subsequent disease rates . But , because of the diluting effects of r and om fluctuations in DBP , these substantially underestimate the true associations of the usual DBP ( ie , an individual 's long-term average DBP ) with disease . After correction for this " regression dilution " bias , prolonged differences in usual DBP of 5 , 7.5 , and 10 mm Hg were respectively associated with at least 34 % , 46 % , and 56 % less stroke and at least 21 % , 29 % , and 37 % less CHD . These associations are about 60 % greater than in previous uncorrected analyses . ( This regression dilution bias is quite general , so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths . ) The DBP results suggest that for the large majority of individuals , whether conventionally " hypertensive " or " normotensive " , a lower blood pressure should eventually confer a lower risk of vascular disease AIMS To investigate the short-term ( 16 weeks ) effect of lifestyle intervention on insulin sensitivity , anthropometric and metabolic variables in non-diabetic first-degree relatives of type 2 diabetic patients ( FDR ) . METHODS Seventy-seven ( 49 male , 28 female ) FDR were allocated to one of three groups , diet ( D-group ; n = 25 ) , diet and exercise ( DE-group ; n = 30 ) or control group ( C-group ; n = 22 ) . Lifestyle counselling was based on current nutrition recommendations , including increased intake of fatty fish and low glycaemic index foods . Group counselling was given on two occasions with follow-up through telephone interviews every 10 days . Assessment s included insulin sensitivity index ( Si ) , anthropometry , lipid parameters , circulating leptin and adiponectin levels . RESULTS The D-group reduced total cholesterol ( -0.31 mmol/l , P = 0.024 ) , LDL cholesterol ( -0.22 mmol/l , P = 0.021 ) and apolipoprotein B ( -9.5 mg/dl , P = 0.009 ) levels , whereas the DE-group decreased body weight ( -2.1 % , P = 0.030 ) and waist circumference ( -3.0 cm , P < 0.001 ) versus controls . A 13 % reduction in fasting insulin was observed in the DE-group , but no significant improvement in Si in D-group or DE-group was observed . A subgroup , adherent to diet and who increased exercise , significantly improved Si and lipid profile . CONCLUSIONS The improved metabolic risk profile in FDR suggests that lifestyle changes can be effective in individuals at high risk to develop type 2 diabetes and cardiovascular disease 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 Thirty-five patients with mild to moderate hypertension were r and omised into a three months ' dietary advised and a three months ' control group . The diet was of a composition currently considered to be appropriate , and was monitored by a dietitian . Statistically significant decreases in diastolic blood pressure , mean arterial pressure , sodium excretion , and low density lipoprotein (LDL)-cholesterol occurred in the intervention group , although differences in change between the intervention and the control group were , except for LDL-cholesterol , not statistically significant . Thus , it did not become clear whether and to what extent change in diet was responsible for the lowering of the blood pressure in the intervention group 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 serum-cholesterol-lowering ( SCL ) diet , was carried out in 2 mental hospitals near Helsinki in 1959 - -71 . The subjects were hospitalized middle-aged men . One of the hospitals received the SCL diet , i.e. a diet low in saturated fats and cholesterol and relatively high in polyunsaturated 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 6 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 about half that during the normal-diet periods . An examination of a number of potential confounding variables indicated that the changes in them were small and failed to account for the considerable reduction in the incidence of CHD . It is concluded that the use of the serum-cholesterol-lowering diet exerted a substantial preventive effect on CHD 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 In this study the authors examined psychosocial variables as mediators for fruit and vegetable ( FV ) intake in a clustered , r and omized effectiveness trial conducted in African American churches . The study sample included 14 churches ( 8 intervention and 6 control ) with 470 participants from the intervention churches and 285 participants from the control churches . The outcome of FV intake and the proposed mediators were measured at baseline and at 6-month follow-up . Structural equation modeling indicated that the intervention had direct effects on social support , self-efficacy , and autonomous motivation ; these variables also had direct effects on FV intake . Applying the M. E. Sobel ( 1982 ) formula to test significant mediated effects , the authors confirmed that social support and self-efficacy were significant mediators but that autonomous motivation was not . Social support and self-efficacy partially mediated 20.9 % of the total effect of the intervention on changes in FV intake . The results support the use of strategies to increase social support and self-efficacy in dietary intervention programs 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 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 To examine a long-term effect of community-based education program for hypercholesterolemia and an effect modification by apolipoprotein E polymorphism , we conducted a 1-year r and omized clinical trial with 8 year-follow-up . One hundred four persons aged 40 - 64 years who had serum total cholesterol levels between 6.21 and 7.73 mmol/l ( 240 and 299 mg/dl ) in 1988 - 89 cardiovascular risk surveys were enrolled in the trial . The intervention group ( n=51 , 82 % for women ) attended eight education classes in 1 year , while the control group ( n=53 , 85 % for women ) attended only two classes . Both groups were invited to the subsequent annual surveys . The mean serum cholesterol was 0.24 - 0.26 mmol/l less in the intervention than in the control group at both 6 month and 1 year ( P=0.03 , each ) while the proportion of subjects using hypolipidemic agents was 0 and 6 % in both groups , respectively . During 8-year follow-up , the probability of using hypolipidemic agents and /or total cholesterol > or = 7.76 mmol/l was 51 % in the education group and 69 % in the control group ; the risk ratio in the intervention vs control groups was 0.62 ( 95 % CI : 0.36 - 1.06 ) . When stratified by the apolipoprotein E polymorphism examined for 78 % of the subjects , the risk ratio was 0.61 ( 0.31 - 1.18 ) among subjects without e4 allele ( n=59 ) and 0.55 ( 0.14 - 2.14 ) among those with e4 allele ( n=22 ) . The intervention group had reduced intake of egg , fish egg , butter , mayonnaise and fatty meat compared to the control group at 6-month , 1- and 8-year follow-up . In conclusion , our community-based program was effective in reducing serum total cholesterol levels non-pharmacologically during the first year , and also reduced the likelihood of progressive worsening of hypercholesterolemia during the subsequent 8 years , regardless of the apolipoprotein E polymorphism 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 Objective To assess whether dietary intervention in free-living healthy subjects is effective in improving blood pressure levels . Design Open r and omised , controlled trial . Setting Free-living healthy subjects in two rural villages in north-eastern Japan . Participants Five hundred and fifty healthy volunteers aged 40–69 years . Interventions Tailored dietary education to encourage a decrease in sodium intake and an increase in the intake of vitamin C and carotene , and of fruit and vegetables . Main outcome measures Blood pressure , dietary intake and urinary excretion of sodium , dietary carotene and vitamin C , and fruit and vegetable intake data were collected at 1 year after the start of the intervention . Results During the first year , changes differed significantly between the intervention and control groups for dietary ( P = 0.002 ) and urinary excretion ( P < 0.001 ) of sodium and dietary vitamin C and carotene ( P = 0.003 ) . Systolic blood pressure decreased from 127.9 to 125.2 mmHg ( 2.7 mmHg decrease ; 95 % confidence interval , −4.6 to −0.8 ) in the intervention group , whereas it increased from 128.0 to 128.5 mmHg ( 0.5 increase ; −1.3 to 2.3 ) in the control group . This change was statistically significant ( P = 0.007 ) . In contrast , the change in diastolic blood pressure did not significantly differ between the groups . In hypertensive subjects , a significant difference in systolic blood pressure reduction was seen between the groups ( P = 0.032 ) . Conclusion Moderate-intensity dietary counseling in free-living healthy subjects achieved significant dietary changes , which result ed in a significant decrease in systolic blood pressure BACKGROUND We report process data on the feasibility of delivering a clinical preventive nutrition intervention that was effective in increasing participants ' consumption of fruits and vegetables . We also examine relationships between process variables and study outcomes . METHODS We r and omly assigned six practice sites in a managed care organization to a dietary intervention or control condition . We invited adults 18 years of age or older scheduled for routine health visits within the subsequent 2 months to participate . Of the 566 patients we contacted from the intervention sites , 230 ( 41 % ) enrolled . From the control sites , we contacted 617 , and 274 ( 44 % ) enrolled . Intervention participants received a tailored letter providing feedback on their consumption of target foods together with recommendations for improvement , stage-matched nutrition education booklets , a diet-health endorsement from their primary care providers ( PCPs ) , and two motivational counseling telephone calls . Of enrollees , 195 ( 85 % ) in the intervention group and 252 ( 92 % ) in the control group returned the final survey 3 months later . RESULTS Seventy-one percent of both participants and PCPs reported that the PCPs had discussed the relationship between diet and health at their visit . Fifty-seven percent of participants and 62 % of PCPs reported that they discussed the complete diet-health endorsement , which included : ( 1 ) acknowledgment of the relationship between diet and health and ( 2 ) tailored study recommendations . The inclusion of both parts of the diet-health endorsement , but not the length of time spent , appeared to correlate with healthful outcomes . CONCLUSIONS These process data suggest that the brief PCP diet-health endorsement contributed to the intervention effect on fruits and vegetables 1 . Intervention trials in free-living population s have shown relatively small reductions in risk factors for cardiovascular disease , including lipid levels , and have led some to question whether diet is an effective treatment for hyperlipidaemia . However , behaviour change is a complex process and it is possible that st and ard intervention methods fail to motivate people sufficiently to comply with dietary advice.2 . This study applied motivational interviewing , a style of behaviour change counselling , to dietary education for people with hyperlipidaemia . One-hundred and twenty-one patients with hyperlipidaemia who had been referred to a hospital dietetic department for dietary advice were r and omized to receive either st and ard or motivational dietary interventions for a period of 3 months . Outcomes assessed included dietary knowledge , stage of change , dietary intakes , lipid levels and body mass indices . 3 . From baseline , both methods of dietary intervention result ed in self-reported changes in dietary habits and knowledge , statistically significant reductions in intake of total fat ( from 32.8 % to 28.4 % ) , saturated fat ( from 11.4 % to 9.2 % ) and energy intakes [ -239 kcal ( -999.98 kJ)/day ] , and in body mass indices ( -0.45 kg/m2 ) . Serum cholesterol did not change significantly in either intervention group.4 . Motivational and st and ard dietary interventions achieved statistically significant changes in reported dietary knowledge and behaviour , and led to a reduction in body weight , but not serum cholesterol . Whether this lack of effect is real or due to subjects overestimating true dietary change can not be determined . Change in body weight was associated with a reported change in energy intake ; this provides some support for there having been a real change in intake 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 OBJECTIVE To describe two lifestyle prevention strategies tested in first-degree relatives of patients with type 2 diabetes and to present the short-term effects of these strategies on nutrient intake , physical activity pattern , and body weight . DESIGN In this 16-week controlled intervention trial , subjects were assigned to one of three treatment conditions : diet group ( D ) ( n=25 ) , diet and exercise group ( DE ) ( n=30 ) , or control group ( C ) ( n=22 ) . Subjects/ setting Non-diabetic relatives of individuals with diabetes were recruited ( n=77 ; men and women ; age 25 to 55 years ) . INTERVENTION Intervention groups received group counseling on two occasions and follow-up through unannounced telephone interviews every 10 days . Counseling regarding diet and physical activity was based on the Nordic Nutrition Recommendations . In addition , increased intake of fatty fish and low glycemic index foods were recommended . Main outcome measures Changes in diet ( assessed by food frequency question naires ) , leisure time physical activity ( assessed through interviews ) , fatty acid composition of erythrocyte membrane , and body weight . Statistical analysis One-way analysis of variance and Mann-Whitney U test were used to compare changes among groups . RESULTS Compared with the control group , both intervention groups decreased intake of saturated fatty acids ( percent of energy ) , increased intake of dietary fiber , and reduced average glycemic index of the diet . The ratio of n-6:n-3 fatty acids of the erythrocyte membranes decreased , confirming increased intake of fatty fish . Body weight decreased 1.7 kg ( 2.1 % , P=.030 ) in group DE , and physical activity increased in the least-active subjects ( + 70 min/week , P<.01 within group ) . Applications/ Conclusions Healthy individuals with heredity for type 2 diabetes can achieve desired changes in lifestyle factors associated with increased risk for the disease BACKGROUND The National Cancer Institute recommends that Americans eat at least five daily servings of fruits and vegetables . National strategies to increase consumption may not reach minority and lower socioeconomic population s. In a r and omized trial , peer education was tested for effectiveness at increasing fruit and vegetable intake among lower socioeconomic , multicultural labor and trades employees . METHODS Employees ( n = 2091 ) completed a baseline survey and received an 18-month intervention program through st and ard communication channels ( e.g. , workplace mail , cafeteria promotions , and speakers ) . Ninety-three social networks ( cliques ) of employees were identified , which were pair matched on intake . At an interim survey ( during months 8 and 9 ) , 11 cliques no longer existed and 41 matched pairs of cliques containing 905 employees remained , with one clique per pair being r and omly assigned to the peer education intervention . Employees who were central in the communication flow of the peer intervention cliques served as peer educators during the last 9 months of the intervention program . Fruit and vegetable intake was measured with 24-hour intake recall and with food-frequency questions in baseline , outcome ( i.e. , at 18 months ) , and 6-month follow-up surveys . All P values are two-sided . RESULTS By use of multiple regression , statistically significant overall effects of the peer education program were seen in the intake recall ( increase of 0.77 total daily servings ; P<.0001 ) and the food-frequency ( increase of 0.46 total daily servings ; P = .002 ) questions at the outcome survey . The effect on the total number of servings persisted at the 6-month follow-up survey when measured by the intake recall ( increase of 0.41 total daily servings ; P = .034 ) but not the food-frequency ( decrease of 0.04 total daily servings ; P = .743 ) questions . CONCLUSIONS Peer education appears to be an effective means of achieving an increase in fruit and vegetable intake among lower socioeconomic , multicultural adult employees Objectives : Higher plasma micronutrient levels have been associated with decreased cancer risks . The objective of this study was to determine the relative effects of reduced fat and /or increased fruit-vegetable ( FV ) intakes on plasma micronutrient levels . Methods : Healthy , premenopausal women with a family history of breast cancer ( n = 122 ) were r and omized across four diet arms for one year in a 2 × 2 factorial design study : control , low-fat , high fruit-vegetable and combination low-fat/high FV diets . Levels of plasma micronutrients were measured in plasma at 0 , 3 , 6 and 12 months . Results : The high FV intervention , regardless of fat intake , significantly increased α-carotene , β-carotene and vitamin C levels in plasma . Only the combination high FV , low-fat intervention significantly increased plasma β-cryptoxanthin and zeaxanthin levels over time . Although α-tocopherol was not affected , a potential concern is that the low-fat intervention result ed in significantly decreased both γ-tocopherol dietary intakes and plasma levels , regardless of whether or not FV intakes were concomitantly increased . Conclusions : Unlike α-tocopherol , γ-tocopherol plasma levels were decreased by a low fat diet , perhaps because γ-tocopherol is not generally added to foods nor widely used in vitamin E supplements . The decreased dietary intakes and plasma levels of γ-tocopherol with a low-fat diet may have implication s for health risks since the biological functions of the different tocopherol isomers have been reported to be distinct 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 High calorie and fat consumption and the production of free radicals are two major mechanistic pathways between diet and disease . In this study we evaluated the effect of a plant-based diet poor in animal fat and rich in ( n-3 ) fatty acids on fatty acids of serum phospholipids and on the production of reactive oxygen metabolites ( ROMs ) . One hundred and four healthy female postmenopausal volunteers were recruited and r and omized to a dietary intervention or a control group . Dietary intervention included a program of food education and biweekly common meals for 18 weeks . When the intervention and control groups were compared , it was seen that dietary intervention result ed in a significant reduction of saturated fatty acids ( -1.5 % ) and a significant increase in ( n-3 ) fatty acids ( + 20.6 % ) , in particular docosahexaenoic acid ( + 24.8 % ) . We observed that arachidonic acid decreased ( –7.7 % ) , while ( n-6 ) fatty acids did not , and the (n-3)/(n-6 ) polyunsaturated ratio increased significantly ( + 24.1 % ) . As expected , ROMs decreased significantly in the intervention group ( -6 % ) . The results indicated that a plant-based diet can improve the serum fatty acid profile and decrease ROMs production . These results suggest that a plant-based diet may reduce the body 's exposure to oxidative stress OBJECTIVES We report on the results of the Treatwell 5-a-Day study , a worksite intervention aim ed at increasing consumption of fruits and vegetables . METHODS Twenty-two worksites were r and omly assigned to 3 groups : ( 1 ) a minimal intervention control group , ( 2 ) a worksite intervention , and ( 3 ) a worksite-plus-family intervention . The interventions used community-organizing strategies and were structured to target multiple levels of influence , following a socioecological model . Data were collected by self-administered employee surveys before and after the intervention ; the response rate was 87 % ( n = 1359 ) at baseline and 76 % ( n = 1306 ) at follow-up . A process tracking system was used to document intervention delivery . RESULTS After control for worksite , gender , education , occupation , race/ethnicity , and living situation , total fruit and vegetable intake increased by 19 % in the worksite-plus-family group , 7 % in the worksite intervention group and 0 % in the control group ( P = .05 ) . These changes reflect a one half serving increase among workers in the worksite-plus-family group compared with the control group ( P = .018 ) . CONCLUSIONS The worksite-plus-family intervention was more successful in increasing fruit and vegetable consumption than was the worksite intervention . Worksite interventions involving family members appear to be a promising strategy for influencing workers ' dietary habits BACKGROUND The few r and omized community trials in middle-income population s that tried to modify multiple dietary risk factors for cancer only demonstrated small changes . This trial sought to decrease the percent of calories derived from fat and to increase fruit , vegetable , and fiber intake among low-income women served by the Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC ) in Maryl and . METHODS We conducted six-month intervention programs for 1055 women at ten WIC sites ; 1011 women served as controls . Intervention participants were invited to five interactive nutrition sessions and were sent written material s. Controls received usual care . Women were surveyed at baseline , two months post intervention , and one year later . All analyses conducted used an intention-to-treat paradigm . RESULTS Mean differences ( intervention-control ) in change from baseline were for percent calories from fat -1.62 + /- 0.33 % ( P < 0.0001 ) , for consumption of fruits and vegetables 0.40 + /- 0.11 servings ( P = 0.0003 ) , and for fiber intake 1.01 + /- 0.31 grams ( P = 0.001 ) . These differences in change were related in a dose-response relationship to the number of sessions women attended and remained significant one year post-intervention for the first two outcomes . CONCLUSIONS Multiple dietary improvements can be achieved in a low-income population with an effective , multi-faceted intervention program . The changes in this trial exceeded those in previous community trials conducted in higher SES population BACKGROUND The Next Step Trial tested interventions encouraging prevention and early detection practice s in automotive-industry employees at increased colorectal cancer risk . This article describes results of the nutrition intervention promoting low-fat , high-fiber eating patterns . METHODS Twenty-eight worksites ( 5,042 employees at baseline ) were r and omized to a 2-year nutrition intervention including classes , mailed self-help material s , and personalized dietary feedback . Control worksites received no intervention . Nutrition outcomes were assessed by mailed food frequency question naires ( FFQs ) Primary nutrition outcomes included percentage energy from fat and fiber density ( g/1,000 kcal ) at 1 year postr and omization . Secondary outcomes included servings of fruits/vegetables and dietary measures at 2 years postr and omization . Analyses were adjusted for within worksite correlations and baseline covariates . Fifty-eight percent of employees returned FFQs . RESULTS At 1 year , there were modest but statistically significant intervention effects for fat ( -0.9 % en ) , fiber ( + 0.5 g/1,000 kcal ) , and fruits/vegetables ( + 0.2 servings/day ) ( all P < 0.007 ) . At 2 years , due to significant positive changes in control worksites , intervention effects were smaller , significant for fiber only . Intervention effects were larger in younger ( < 50 years ) , active employees and class attendees . CONCLUSION The nutrition intervention produced significant but modest effects on dietary fat and fiber and fruits/vegetables in these high-risk employees . Age and dose effects suggest younger employees may be more responsive to this intervention Aims To compare health effects and risk reduction in two different strategies of nutritional counselling in primary health care for patients at high risk of ischaemic heart disease . Methods In a cluster-r and omized trial 60 general practitioners ( GPs ) in the Copenhagen County were r and omized to give nutritional counselling or to refer patients to a dietician . Patients were included after opportunistically screening ( n = 503 patients ) , and received nutritional counselling by GP or dietician over 12 months . Health effects were measured by changes in weight , waist circumference and blood lipids . Risk of cardiovascular disease was calculated by The Copenhagen Risk Score . Data on use of medicine and primary health care was obtained from central registers . Results Altogether 339 ( 67 % ) patients completed the intervention . Weight loss was larger in the dietician group ( mean 4.5 kg vs. 2.4 kg ) , and increase of HDL-cholesterol was larger in the GP group ( mean 0.13mmol/l vs. 0.03mmol/l ) . The reduction of the cardiovascular risk score was significantly larger in the GP group ( P = 0.0005 ) . Other health outcomes were not significantly different . Conclusions GPs were aware of substantial risk factors of cardiovascular disease and addressed these when counselling . The guidance from a GP was of significant importance for risk reduction in relation to IHD . However , a long-term lifestyle intervention by GP was difficult to implement . In the case of obesity it was effective to refer to long-term nutritional counselling by a dietician Residents of the rural South are at high risk for heart disease and are frequently identified as having high blood cholesterol , but sources for nutrition counseling in rural areas are often limited . To increase the availability of high quality nutrition counseling , the Food for Heart Program was developed for public health nurses and is design ed to circumvent many of the obstacles common to dietary counseling . We conducted a r and omized trial to assess the effectiveness of this program to lower blood cholesterol . In this report , we describe the study design , intervention program , and baseline characteristics of participants . Nurses at 17 health departments screened 781 subjects to enroll 468 with high blood cholesterol : three-quarters of the subjects were female , the mean age was 55 , and 80 % were white . Participants were at high risk for heart disease : 60 % had two or more risk factors for coronary disease , the majority were overweight with a mean BMI of 29 , and the mean cholesterol was 257 mg/dL. Reported baseline dietary intake included relatively modest consumption of high fat meats and snack foods , excessive consumption of sweets , modest intake of complex carbohydrates , and inadequate consumption of fruits and vegetables 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 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 ( enrollment , 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 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 |
2,233 | 12,076,484 | REVIEW ER 'S CONCLUSIONS Implication s for practice The r and omised trials included in this review provide evidence that short course zidovudine and single-dose nevirapine are effective therapies for reducing mother-to-child transmission of HIV . | BACKGROUND At the end of 2000 it was estimated that over 36 million people were living with the human immunodeficiency virus ( HIV ) .
This includes 1.4 million children less than 15 years of age .
This is one of several review s assessing the available evidence for preventing mother-to-child transmission of HIV infection .
OBJECTIVES To assess which antiretroviral therapies may be effective in decreasing the risk of mother-to-child transmission of HIV infection as well as their effect on neonatal and maternal mortality and morbidity .
The challenge for low and middle income countries will be to institute this therapy in practice . | CONTEXT Antenatal counseling and human immunodeficiency virus ( HIV ) testing are not universal in Africa ; thus , women often present in labor with unknown HIV status without receiving the HIVNET 012 nevirapine ( NVP ) regimen ( a single oral dose of NVP to the mother at the start of labor and to the infant within 72 hours of birth ) . OBJECTIVE To determine risk of mother-to-child transmission of HIV when either st and ard use of NVP alone or in combination with zidovudine ( ZDV ) was administered to infants of women tested at delivery . DESIGN , SETTING , AND PARTICIPANTS A r and omized , open-label , phase 3 trial conducted between April 1 , 2000 , and March 15 , 2003 , at 6 clinics in Blantyre , Malawi , Africa . The trial included all infants born to 894 women who were HIV positive , received NVP intrapartum , and were previously antiretroviral treatment-naive . Infants were r and omly assigned to NVP ( n = 448 ) and NVP plus ZDV ( n = 446 ) . Infants were enrolled at birth , observed at 6 to 8 weeks , and followed up through 3 to 18 months . The HIV status of 90 % of all infants was established at 6 to 8 weeks . INTERVENTION Mothers received a 200-mg single oral dose of NVP intrapartum and infants received either 2-mg/kg oral dose of NVP or NVP ( same dose ) plus 4 mg/kg of ZDV twice per day for a week . MAIN OUTCOME MEASURES HIV infection of infant at birth and 6 to 8 weeks , and adverse events . RESULTS The mother-to-child transmission of HIV at birth was 8.1 % ( 36/445 ) in infants administered NVP only and 10.1 % ( 45/444 ) in those administered NVP plus ZDV ( P = .30 ) . A life table estimate of transmission at 6 to 8 weeks was 14.1 % ( 95 % confidence interval [ CI ] , 10.7%-17.4 % ) in infants who received NVP and 16.3 % ( 95 % CI , 12.7%-19.8 % ) in those who received NVP plus ZDV ( P = .36 ) . For infants not infected at birth and retested at 6 to 8 weeks , transmission was 6.5 % ( 23/353 ) in those who received NVP only and 6.9 % ( 25/363 ) in those who received NVP plus ZDV ( P = .88 ) . Almost all infants ( 99%-100 % ) were breastfed at 1 week and 6 to 8 weeks . Grade s 3 and 4 adverse events were comparable ; 4.9 % ( 22/448 ) and 5.4 % ( 24/446 ) in infants receiving NVP only and NVP plus ZDV , respectively ( P = .76 ) . CONCLUSIONS The frequency of mother-to-child HIV transmission at 6 to 8 weeks in our 2 study groups was comparable with that observed for other perinatal HIV intervention studies among breastfeeding women in Africa . The safety of the regimen containing neonatal ZDV was similar to that of a st and ard NVP regimen Almost all childhood HIV-1 is now acquired through vertical transmission . Identifying factors that affect the rate of transmission may lead to the initiation of specific preventive strategies . In this study , antibody levels against different neutralizing epitopes on the envelope glycoprotein of HIV-1 ( gp120 ) were measured in HIV-1-infected pregnant women that either transmitted HIV-1 to their infants ( 18 women ) or did not ( 29 women ) . Differences in levels of antibodies directed against the monomeric gp120 molecule and against the V3 loop region of gp120 were not significantly different between the two groups studied . However , significant differences were observed in the levels of CD4 binding site antibodies , as determined by the ability of diluted maternal plasma to inhibit binding of the CD4 binding site monoclonal antibody F105 ( mAb F105 ) to monomeric gp120 . In addition , more nontransmitting mothers had low viral load as defined by having two or more negative HIV-1 viral cultures during pregnancy compared with transmitters . This pilot study suggests that in addition to higher viral load , low levels of CD4 binding site antibodies correlate with increased risk of HIV-1 vertical transmission . Passive immunotherapy with broadly neutralizing CD4 binding site antibodies should be considered as a strategy to reduce this risk Objectives To study mortality in African children born to HIV-1-infected mothers exposed peripartum to zidovudine . Methods A r and omized placebo-controlled trial in Abidjan and Bobo-Dioulasso . Pregnant women received either 300 mg zidovudine twice daily from 36–38 weeks ’ gestation , 600 mg during labour , and 300 mg twice daily for 7 days post-partum or a matching placebo . Determinants of mortality were studied up to 18 months , overall and among the infected children : treatment , centre , timing of infection , mother and child HIV disease . Results There were 75 infant deaths among 407 live births . The risk of death at 18 months was 176/1000 in the zidovudine arm and 221 for placebo . Relative hazard ( RH , zidovudine versus placebo ) was 0.47 [ 95 % confidence interval ( CI ) 0.2–1.0 ] up to 230 days of life . Maternal CD4 lymphocyte count < 200/mm3 ( RH 2.92 ; CI 1.4–6.1 ) and child HIV-1 infection ( RH 12.6 ; CI 6.6–24.3 ) increased mortality of all children born to HIV-1-infected mothers . There were 101 children infected ( 40 in the zidovudine group ) , and 51 died . Their 18 month probability of death was 590/1000 in the zidovudine group and 510 in the placebo group . Among infected children , maternal zidovudine reduced the risk of death on or before day 230 ( RH 0.18 ; CI 0.1–0.5 ) . Maternal CD4 lymphocyte count < 200/mm3 ( RH 3.25 ; CI 1.3–8.4 ) , maternal death ( RH 9.65 ; CI 1.7–56.0 ) , diagnosis of paediatric infection on or before day 12 ( RH 18.1 ; CI 4.8–69.0 ) and between days 13 and 45 ( RH 7.63 ; CI 2.0–29.5 ) , clinical paediatric AIDS ( RH 5.37 ; CI 2.3–12.7 ) were risk factors for death in HIV-1-infected children . Conclusion Mother-to-child transmission reduction by zidovudine is safe and beneficial to African children . The mortality of HIV-1-infected children is high . Peripartum maternal zidovudine exerts a protective effect for at least 8 months BACKGROUND The AIDS Clinical Trials Group protocol 076 zidovudine prophylaxis regimen for HIV-1-infected pregnant women and their babies has been associated with a significant decrease in vertical HIV-1 transmission in non-breastfeeding women in developed countries . We compared the safety and efficacy of short-course nevirapine or zidovudine during labour and the first week of life . METHODS From November , 1997 , to April , 1999 , we enrolled 626 HIV-1-infected pregnant women at Mulago Hospital in Kampala , Ug and a. We r and omly assigned mothers nevirapine 200 mg orally at onset of labour and 2 mg/kg to babies within 72 h of birth , or zidovudine 600 mg orally to the mother at onset of labour and 300 mg every 3 h until delivery , and 4 mg/kg orally twice daily to babies for 7 days after birth . We tested babies for HIV-1 infection at birth , 6 - 8 weeks , and 14 - 16 weeks by HIV-1 RNA PCR . We assessed HIV-1 transmission and HIV-1-free survival with Kaplan-Meier analysis . FINDINGS Nearly all babies ( 98.8 % ) were breastfed , and 95.6 % were still breastfeeding at age 14 - 16 weeks . The estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were : 10.4 % and 8.2 % at birth ( p=0.354 ) ; 21.3 % and 11.9 % by age 6 - 8 weeks ( p=0.0027 ) ; and 25.1 % and 13.1 % by age 14 - 16 weeks ( p=0.0006 ) . The efficacy of nevirapine compared with zidovudine was 47 % ( 95 % CI 20 - 64 ) up to age 14 - 16 weeks . The two regimens were well tolerated and adverse events were similar in the two groups . INTERPRETATION Nevirapine lowered the risk of HIV-1 transmission during the first 14 - 16 weeks of life by nearly 50 % in a breastfeeding population . This simple and inexpensive regimen could decrease mother-to-child HIV-1 transmission in less-developed countries BACKGROUND Short-course zidovudine ( ZDV ) given in the late antenatal period can reduce mother-infant human immunodeficiency virus ( HIV ) transmission by one half . Because this intervention is being implemented in developing countries , evidence of its safety is needed . METHODS In a r and omized , double-blinded , placebo-controlled trial in Bangkok , HIV-infected pregnant women received either ZDV ( 300 mg twice daily from 36 weeks ' gestation until labor , then every 3 hours until delivery ) or an identical placebo regimen . Infants were evaluated at birth and at 1 , 2 , 4 , 6 , 9 , 12 , 15 , and 18 months of age . Growth , clinical events , and hematologic and immunologic measurements were compared between treatment groups . RESULTS Of the 395 children born ( 196 in ZDV group and 199 in placebo group ) , 330 were uninfected , 55 were infected , and 10 had indeterminate infection status . Overall , 319 children ( 81 % ) completed 18 months of follow-up , and 14 ( 4 % ) died before 18 months of age . Among uninfected children , the mean hematocrit was lower in the ZDV group at birth ( 49.1 % vs 51.5 % ) but not at later ages ; mean weight , height , head circumference , and CD4(+ ) and CD8(+ ) T lymphocyte counts were similar in both groups at all ages . Five uninfected children in the ZDV group but only one in the placebo group had a febrile convulsion . No other signs suggestive of mitochondrial dysfunction and no tumors were observed . Among infected children , an estimated 62 % in the ZDV group and 77 % in the placebo group survived free of Centers for Disease Control and Prevention class C disease during the 18-month follow-up . CONCLUSIONS No significant adverse events were associated with short-course ZDV during 18 months of follow-up in this population BACKGROUND The clinical presentation of HIV-1 related diseases could have changed after the introduction of highly active antiretroviral treatment ( HAART ) . We aim ed to assess changes over time in the incidence of ADIs overall and within CD4 lymphocyte count strata , the relationship with treatment and degree of immunodeficiency at diagnosis of ADIs . METHODS We did a prospect i ve observational multicentre study of over 7300 patients in 52 European HIV-1 outpatient clinics . Incidence rates per 100 patient-years of observation were calculated . FINDINGS In total , we recorded 1667 new ADIs ; the incidence of ADIs declined from 30.7 per 100 patient-years of observation during 1994 ( 95 % CI 28.0 - 33.4 ) to 2.5 per 100 patient-years of observation during 1998 ( 95 % CI 2.0 - 3.0 , p<0.0001 , test for trend ) . Median CD4 lymphocyte count at diagnosis of a new ADI increased from 28 cells/microL to 125 cells/microL between 1994 and 1998 ( p<0.0001 ) , yet a steep decline in the rate of ADIs was seen after stratification by latest CD4 lymphocyte count within each year ( < or = 50 , 51 - 200 , and > 200 cells/microL ) . Patients on HAART had a lower rate of ADIs than patients not on this treatment within each CD4 lymphocyte count strata . The proportion of ADIs attributable to cytomegalovirus retinitis and Mycobacterium avium complex declined over time ( p=0.0058 and 0.0022 , respectively ) , whereas the proportion of diagnoses attributable to non-Hodgkin lymphoma has increased ( p<0.0001 ) . In 1994 , less than 4 % of ADIs were non-Hodgkin lymphoma , in 1998 the proportion was almost 16 % . This condition has become one of the most common ADIs in patients on HAART . INTERPRETATION Our findings lend support to the idea that treatment regimens can lower the incidence of ADIs . The immediate risk of an ADI for a given CD4 lymphocyte count has declined over time and is lower among patients on HAART . Long-term follow-up of patients on combination treatment is essential to monitor the incidence of new and emerging diagnoses The safety , toxicity , and pharmacokinetics of intrapartum and early newborn nevirapine were evaluated in 17 human immunodeficiency virus type 1-infected women in labor and their newborns . No adverse effects of nevirapine were noted in any study mothers or infants . Following maternal dosing with 200 mg during labor , concentrations exceeding 100 ng/mL ( 10 times the in vitro IC50 ) were achieved in the newborns . Nevirapine elimination was prolonged in both mothers and infants , with median half-lives ranging from 36.8 to 65.7 h. Administration of 200 mg orally to the mothers in labor and of a single 2-mg/kg oral dose to the infants at 48 - 72 h after birth maintained serum concentrations in the infants > 100 ng/mL through 7 days of life BACKGROUND Although zidovudine prophylaxis decreases the rate of transmission of the human immunodeficiency virus ( HIV ) type 1 substantially , a large number of infants still become infected . We hypothesized that the administration , in addition to zidovudine , of a single dose of oral nevirapine to mothers during labor and to neonates would further reduce transmission of HIV . METHODS We conducted a r and omized , double-blind trial of three treatment regimens in Thai women who were receiving zidovudine therapy during the third trimester of pregnancy . In one group , mothers and infants received a single dose of nevirapine ( nevirapine-nevirapine regimen ) ; in another , mothers and infants received nevirapine and placebo , respectively ( nevirapine-placebo regimen ) ; and in the last , mothers and infants received placebo ( placebo-placebo regimen ) . The infants also received one week of zidovudine therapy and were formula-fed . The end point of the study was infection with HIV in the infants , established by virologic testing . RESULTS Between January 15 , 2001 , and February 28 , 2003 , a total of 1844 Thai women were enrolled . At the first interim analysis , the independent data monitoring committee stopped enrollment in the placebo-placebo group . Among women who delivered before the interim analysis , the as-r and omized Kaplan-Meier estimates of the transmission rates were 1.1 percent ( 95 percent confidence interval , 0.3 to 2.2 ) in the nevirapine-nevirapine group and 6.3 percent ( 95 percent confidence interval , 3.8 to 8.9 ) in the placebo-placebo group ( P<0.001 ) . The final per- protocol transmission rate in the nevirapine-nevirapine group , 1.9 percent ( 95 percent confidence interval , 0.9 to 3.0 ) , was not significantly inferior to the rate in the nevirapine-placebo group ( 2.8 percent ; 95 percent confidence interval , 1.5 to 4.1 ) . Nevirapine had an effect within subgroups defined by known risk factors such as viral load and CD4 count . No serious adverse effects were associated with nevirapine therapy . CONCLUSIONS A single dose of nevirapine to the mother , with or without a dose of nevirapine to the infant , added to oral zidovudine prophylaxis starting at 28 weeks ' gestation , is highly effective in reducing mother-to-child transmission of HIV Objective : To compare compliance and infant HIV-1 infection risk at 6 weeks with the Thai-CDC and HIVNET-012 antiretroviral regimens in a field setting . Design : R and omized clinical trial . Setting : Tertiary hospital antenatal clinic in Nairobi , Kenya . Participants : HIV-1 infected women referred from primary care clinics . Interventions : Thai-CDC zidovudine regimen or HIVNET-012 nevirapine regimen . Main outcome measures : Women were considered compliant if they used ⩾ 80 % of the doses . Infants were tested for HIV-1 at 6 weeks . Results : Seventy women were r and omized to Thai-CDC and 69 to HIVNET-012 regimens . More women were compliant with the antenatal ( 86 % ) than the intrapartum ( 44 % ) Thai-CDC regimen doses ( P = 0.001 ) . Ninety-seven per cent took the maternal and 91 % gave the infant dose of the HIVNET-012 regimen ( P = 0.2 ) . Overall , 41 % were compliant with the Thai-CDC regimen and 87 % with the HIVNET-012 regimen ( P < 0.001 ) . Compliance with the Thai-CDC regimen was associated with partner support of antiretroviral use [ odds ratio ( OR ) , 3.0 ; , 95 % confidence interval ( CI ) , 1.0–9.1 ] and knowledge at recruitment that antiretroviral drugs could prevent infant HIV-1 ( OR , 2.9 ; 95 % CI , 1.0–8.1 ) . Compliance with the HIVNET-012 regimen was associated with partner notification ( OR , 8.0 ; 95 % CI , 1.5–50 ) and partner willingness to have HIV-1 testing ( OR , 7.5 ; 95 % CI , 1.4–40 ) . There was a trend for a higher risk of transmission with the HIVNET-012 regimen than with the Thai-CDC regimen ( 22 % versus 9 % ; P = 0.07 ) . Conclusion : Compliance with the Thai-CDC and HIVNET-012 regimens was comparable to that in efficacy trials . Partner involvement , support and education on perinatal HIV-1 prevention may improve compliance and increase the number of infants protected from HIV-1 infection BACKGROUND AND METHODS Maternal-infant transmission is the primary means by which young children become infected with human immunodeficiency virus type 1 ( HIV ) . We conducted a r and omized , double-blind , placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission . HIV-infected pregnant women ( 14 to 34 weeks ' gestation ) with CD4 + T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled . The zidovudine regimen included antepartum zidovudine ( 100 mg orally five times daily ) , intrapartum zidovudine ( 2 mg per kilogram of body weight given intravenously over one hour , then 1 mg per kilogram per hour until delivery ) , and zidovudine for the newborn ( 2 mg per kilogram orally every six hours for six weeks ) . Infants with at least one positive HIV culture of peripheral-blood mononuclear cells were classified as HIV-infected . RESULTS From April 1991 through December 20 , 1993 , the cutoff date for the first interim analysis of efficacy , 477 pregnant women were enrolled ; during the study period , 409 gave birth to 415 live-born infants . HIV-infection status was known for 363 births ( 180 in the zidovudine group and 183 in the placebo group ) . Thirteen infants in the zidovudine group and 40 in the placebo group were HIV-infected . The proportions infected at 18 months , as estimated by the Kaplan-Meier method , were 8.3 percent ( 95 percent confidence interval , 3.9 to 12.8 percent ) in the zidovudine group and 25.5 percent ( 95 percent confidence interval , 18.4 to 32.5 percent ) in the placebo group . This corresponds to a 67.5 percent ( 95 percent confidence interval , 40.7 to 82.1 percent ) relative reduction in the risk of HIV transmission ( Z = 4.03 , P = 0.00006 ) . Minimal short-term toxic effects were observed . The level of hemoglobin at birth in the infants in the zidovudine group was significantly lower than that in the infants in the placebo group . By 12 weeks of age , hemoglobin values in the two groups were similar . CONCLUSIONS In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy , a regimen consisting of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds CONTEXT Underst and ing the risk of human immunodeficiency virus ( HIV ) transmission through breastfeeding is essential for advising HIV-infected mothers and formulating public health policy recommendations . OBJECTIVE To measure the frequency , timing , and risk factors of HIV transmission through breast milk . DESIGN Prospect i ve cohort study conducted between 1994 and 1997 , with follow-up of infants through 24 months of age . SETTING Postnatal clinic of tertiary care hospital , Blantyre , Malawi . PARTICIPANTS A total of 672 infants ( HIV-negative at birth ) born to HIV-infected women who had not received antiretroviral drugs during or after pregnancy . MAIN OUTCOME MEASURE Incidence of HIV in breastfed infants by age and maternal and infant risk factors for HIV transmission , using proportional hazard models to derive risk ratios ( RRs ) and 95 % confidence intervals ( CIs ) . RESULTS Forty-seven children became HIV-infected while breastfeeding but none after breastfeeding had stopped . The cumulative infection rate while breastfeeding , from month 1 to the end of months 5 , 11,17 , and 23 , was 3.5 % , 7.0 % , 8.9 % , and 10.3 % , respectively . Incidence per month was 0.7 % during age 1 to 5 months , 0.6 % during age 6 to 11 months , and 0.3 % during age 12 to 17 months ( P = .01 for trend ) . The only factors significantly associated with low risk of postnatal HIV transmission in a multivariate model were high maternal parity ( RR , 0.23 ; 95 % CI , 0.09 - 0.56 ) and older maternal age ( RR , 0.44 ; 95 % CI , 0.23 - 0.84 ) . CONCLUSIONS Our data suggest that the risk of HIV infection is highest in the early months of breastfeeding , which should be considered in formulating breastfeeding policy recommendations To determine the efficacy and safety of 2 inexpensive and easily deliverable antiretroviral ( ARV ) regimens for the prevention of mother-to-child transmission ( MTCT ) of human immunodeficiency virus ( HIV ) type 1 during labor and delivery , HIV-infected pregnant women were screened at 11 maternity health institutions in South Africa and were enrolled in an open-label short course ARV regimen of either nevirapine ( Nvp ) or multiple-dose zidovudine and lamivudine ( Zdv/3TC ) . The overall estimated HIV-1 infection rates in 1307 infants by 8 weeks were 12.3 % ( 95 % confidence interval [ CI ] , 9.7 - 15.0 ) for Nvp and 9.3 % ( 95 % CI , 7.0 - 11.6 ) for Zdv/3TC ( P=.11 ) . Excluding infections detected within 72 h ( intrauterine ) , new HIV-1 infections were detected in 5.7 % ( 95 % CI , 3.7 - 7.8 ) and 3.6 % ( 95 % CI , 2.0 - 5.3 ) of infants in the Nvp and Zdv/3TC groups , respectively , in the 8 weeks after birth . There were no drug-related maternal or pediatric serious adverse events . Common complications were obstetrical for mothers ( Nvp group , 24.3 % ; Zdv/3TC group , 26.3 % ) and respiratory for infants ( Nvp group , 16.1 % ; Zdv/3TC group , 17.0 % ) . This study further confirms the efficacy and safety of short-course ARV regimens in reducing MTCT rates in developing countries Short-course antiretroviral regimens have been evaluated to reduce mother-to-child transmission of HIV in re source -limited setting s. This report from Abidjan , Cote d'Ivoire , examines the risk factors for HIV transmission by 1 and 24 months among breast-feeding women . Eligible HIV-1–seropositive pregnant women enrolled in this r and omized double-blind clinical trial were r and omly assigned to receive either oral zidovudine ( ZDV ) ( n = 126 ) prophylaxis or placebo ( n = 124 ) . Maternal prophylaxis began at 36 weeks of gestation ( 300 mg ZDV twice daily antepartum and 300 mg every 3 hours intrapartum ) ; there was no neonatal prophylaxis component . The cumulative risk of transmission in the treatment group was 11.9 % and 22.1 % by 1 and 24 months , respectively . In adjusted analyses , viral load at enrollment was the strongest predictor of transmission ( per log increment : odds ratio [ OR ] = 4.8 , 95 % confidence interval [ CI ] : 2.5–9.5 at 1 month ; OR = 5.7 ; 95 % CI : 3.1–10.8 at 24 months ) . Overall , ZDV prophylaxis was not significantly protective for infection at 1 or 24 months . Comparing ZDV with placebo following dichotomization of viral load ( < 50,000 vs. ≥50,000 copies/mL ) at enrollment , however , there was a significant effect of ZDV seen only among those women with a low viral load at enrollment . The substantial risk of transmission despite ZDV prophylaxis , particularly among those with higher viral loads , underscores the need to find more effective regimens appropriate for use in re source -limited setting The goal of this exercise was to provide estimates of the mother-to-child transmission rate ( TR ) of human immunodeficiency virus type 1 ( HIV-1 ) , calculated according to st and ardized methods . Prospect i ve cohort studies in Africa ( 8) , the Caribbean ( 1 ) , Europe ( 3 ) , and the U.S.A. ( 1 ) observed from birth children born to women known to be HIV infected at the time of delivery . TRs were calculated and compared by investigators during a meeting in Ghent ( Belgium ) in September 1993 according to agreed methodology . TRs were calculated following the direct and the indirect methods developed in 1992 by the Ghent Working Group . The direct method uses a classification of children born to HIV-seropositive mothers according to their probable HIV infection status at 15 months of age or before , if they die or are lost to follow-up . Minimum , intermediate , and maximum estimates of TR are computed depending on how children classified as indeterminate are counted . The indirect method is applied for studies with a comparison cohort of children born to HIV-seronegative mothers . TRs in developed countries ranged from 14 to 25 % with the direct method ( intermediate estimate ) . In the developing world , they ranged from 13 to 42 % with the direct method , from 21 to 43 % with the indirect method , and most of the studies reported a TR in the range of 25 to 30 % . With use of a st and ardized methodology , the overall TR of HIV-1 tends to be higher in Africa than in Europe or the U.S.A. ( ABSTRACT TRUNCATED AT 250 WORDS CONTEXT With the success of zidovudine chemoprophylaxis for prevention of perinatal transmission of the human immunodeficiency virus ( HIV ) , an increasing number of HIV-exposed but uninfected children will have in utero exposure to zidovudine and other antiretroviral drugs . OBJECTIVE To evaluate the long-term effects of in utero exposure to zidovudine vs placebo among a r and omized cohort of uninfected children . DESIGN Prospect i ve cohort study based on data collected during Pediatric AIDS Clinical Trials Group Protocol 076 , a perinatal zidovudine HIV prevention trial , and Protocol 219 , a long-term observational protocol . SETTING Pediatric research clinics in the United States . PATIENTS Two hundred thirty-four uninfected children born to 230 HIV-infected women enrolled in Protocol 076 and followed up through February 28 , 1997 , in Protocol 219 ( 122 in the zidovudine group and 112 in the placebo group ) . MAIN OUTCOME MEASURES Physical growth measurements , immunologic parameters , cognitive/developmental function , occurrence of neoplasms , and mortality data assessed every 6 months for children younger than 24 months and yearly thereafter or as clinical ly indicated . Baseline echocardiogram and funduscopic evaluations were collected before 36 months of age . RESULTS Median age of children at time of last follow-up visit was 4.2 years ( range , 3.2 - 5.6 years ) . There were no significant differences between children exposed to zidovudine and those who received placebo in terms of sequential data on lymphocyte subsets ; weight , height , and head circumference z scores ; and cognitive/developmental function . No deaths or malignancies occurred . Two children ( both exposed to zidovudine ) are being followed up for abnormal , unexplained ophthalmic findings . One child exposed to zidovudine had a mild cardiomyopathy on echocardiogram at the age of 48 months ; the child is clinical ly asymptomatic . CONCLUSIONS No adverse effects were observed in HIV-uninfected children with in utero and neonatal exposure to zidovudine followed up for as long as 5.6 years . Continued prospect i ve evaluations of children born to HIV-infected women who are exposed to antiretroviral or immunotherapeutic agents are critical to assess the long-term safety of interventions that prevent perinatal HIV transmission In this prospect i ve study of infants born to human immunodeficiency virus ( HIV ) seropositive mothers , neonatal and maternal characteristics of infected and noninfected infants were compared to determine the factors that may be associated with or contribute to vertical transmission of HIV . Of 134 infants entered as newborns in the study , 31 have definite serological and /or clinical evidence of infection and 103 are considered noninfected ( transmission rate , 23.1 % ) . Significantly more of the infected infants had birth weights below 2,500 g ( 48.4 % versus 22.3 % ) , and more infected infants were found to be small for gestational age ( 16.2 % versus 5.8 % ) . A greater number of infected infants experienced two or more problems in the neonatal period than noninfected infants ( 51.6 % versus 24.2 % ) . The incidence of confirmed and suspected bacterial infections was also significantly increased in the infected group . Multiple logistic regression analysis indicated low birth weight had the strongest association with vertical transmission of HIV . There was no significant difference between the two groups in mean maternal age at first pregnancy , mother 's marital status , education , type of family , or past history of type of substances abused . Mothers who transmitted HIV to their infants had a trend towards a higher frequency of clinical chorioamnionitis ( 16.1 % versus 5.8 % ) , reported sexually transmitted diseases during pregnancy ( 45.2 % versus 22.3 % ) , and continued illicit drug use ( 67.7 % versus 49.0 % ) . In this group of infants , low birth weight , poor intrauterine growth , neonatal infections and possibly maternal chorioamnionitis , STDs during pregnancy , and continued drug use are associated with vertical transmission of HIV Context : Despite the success of highly active antiretroviral therapy , the optimal approach for preventing perinatal HIV‐1 transmission is not known . Objective : A retrospective survey was conducted at six centers in the United States and Puerto Rico from January 1997 to October 1998 to evaluate the effects of protease inhibitor use during pregnancy on maternal and infant safety , prematurity rate , and frequency of perinatal HIV‐1 transmission . Results : In the study , 91 live infants , including 3 sets of twins , and 1 neonate who died shortly after birth were born to 89 women . HIV perinatal transmission rate in this series was 0 ( 95 % confidence interval [ CI ] , 0%‐3 % ) . Prematurity rate was 19.1 % , comparable to rates in earlier reports of HIV‐1‐infected women . In multiple regression analysis , only cocaine use and premature rupture of membranes were associated with prematurity ( p = .03 and .008 , respectively ) . The gestational week during which the protease inhibitors were initiated was not found to be significantly associated with prematurity . Adverse maternal , obstetric , and infant events possibly related to protease inhibitors were uncommon . Conclusions : Protease inhibitors appeared generally safe in mothers and infants in this series . No perinatal HIV‐1 transmission occurred . Further prospect i ve , controlled studies are needed to define the optimal management of HIV‐1 in pregnancy CONTEXT A 2-dose intrapartum/newborn nevirapine regimen reduced perinatal human immunodeficiency virus ( HIV ) transmission in Ug and an women not receiving antenatal antiretroviral therapy ( ART ) . However , it is unknown whether the addition of the 2-dose nevirapine regimen to st and ard ART would further reduce perinatal HIV transmission . OBJECTIVE To determine whether a 2-dose nevirapine regimen can decrease perinatal transmission of HIV in nonbreastfeeding women receiving st and ard ART . DESIGN AND SETTING International , blinded , placebo-controlled , phase 3 trial enrolling women between May 1997 and June 2000 at clinical sites providing care for HIV infection throughout the United States , Europe , Brazil , and the Bahamas . PARTICIPANTS A total of 1270 women received nevirapine ( n = 642 ) or placebo ( n = 628 ) . Infants were followed up for 6 months to determine HIV-infection status , which was available for 1248 deliveries . INTERVENTION A 200-mg dose of oral nevirapine to women after onset of labor and a 2-mg/kg dose of oral nevirapine to newborns between 48 and 72 hours after birth . MAIN OUTCOME MEASURES Detection of HIV infection in infants and grade 3 and 4 toxic effects in women and newborns . RESULTS After review by the data and safety monitoring board , the trial was stopped early because the overall transmission rates were significantly lower than assumed for the study design . Antenatal ART included zidovudine alone in 23 % ; combinations without protease inhibitors in 36 % ; and combinations with protease inhibitors in 41 % . Thirty-four percent of women had elective cesarean delivery . No significant safety concerns were identified for women or infants . Detection of HIV infection occurred in 9 ( 1.4 % ; 95 % confidence interval [ CI ] , 0.6%-2.7 % ) of 631 nevirapine group deliveries and 10 ( 1.6 % ; 95 % CI , 0.8%-2.9 % ) of 617 placebo group deliveries . The 95 % CI for the difference in transmission rate ( -0.2 ) between the 2 study arms ranged from -1.5 % in favor of nevirapine to 1.2 % in favor of placebo ( P = .82 , Fisher exact test ) . The transmission rate was higher in women with lower baseline CD4 cell counts and higher delivery HIV RNA levels , but there was no significant difference between treatment arms in any subgroup . CONCLUSION Risk of perinatal HIV transmission was low and no benefit from additional intrapartum/newborn nevirapine was demonstrated when women received prenatal care and antenatal ART , and elective cesarean section was made available Objectives : To evaluate tolerance for the oral administration of zidovudine ( ZDV ) during labor and measure the result ing ZDV concentrations in umbilical cord blood . Design : A cross-sectional study of women in a placebo-controlled trial of short-course ZDV ( twice a day from 36 weeks ' gestation until labor and every 3 h during labor ) to prevent perinatal HIV transmission in Bangkok . Methods : Umbilical cord blood was collected . Sixty control specimens and specimens from 372 women ( 182 in the ZDV group , 190 in the placebo group ) were tested for ZDV by radioimmunoassay ( lower detection limit < 1 ng/ml ) . Results : All women in the ZDV group took one or more labor dose , 170 ( 93 % ) took their last dose within 3 h of delivery , and only five ( 3 % ) experienced nausea or vomiting , a proportion similar to the placebo group . The median concentration of ZDV in the cord blood in the ZDV group was 252 ng/ml ( range , < 1–1133 ng/ml ) ; 31 ( 17 % ) specimens were less than 130 ng/ml ( 0.5 μM ) , the concentration thought to be active against HIV in vitro . Median concentrations were 189 ng/ml in specimens from women taking one or two labor doses , 290 ng/ml in those taking three or four doses , and 293 ng/ml in those taking more than four doses ( P < 0.01 ) . The ZDV concentration was not associated with time since the last dose , body weight , or perinatal transmission . Conclusion : Oral intrapartum ZDV was feasible and well tolerated . Most ZDV concentrations in the cord blood after oral dosing during labor were at therapeutic concentrations but were lower than those reported after continuous intravenous administration . Although concentrations were not associated with perinatal transmission , these data do not exclude the possibility that intrapartum and neonatal chemoprophylaxis is effective BACKGROUND A single intrapartum dose of nevirapine for the prevention of mother-to-child transmission of human immunodeficiency virus ( HIV ) leads to the selection of resistance mutations . Whether there are clinical ly significant consequences in mothers who are subsequently treated with a nevirapine-containing regimen is unknown . METHODS We r and omly assigned 1844 women in Thail and who received zidovudine during the third trimester of pregnancy to receive intrapartum nevirapine or placebo . In the postpartum period , 269 of the women with a CD4 count below 250 cells per cubic millimeter began a nevirapine-containing antiretroviral regimen . Plasma sample s were obtained 10 days post partum and analyzed for resistance mutations . Plasma HIV type 1 ( HIV-1 ) RNA was measured before the initiation of therapy and three and six months thereafter . RESULTS After six months of therapy , the HIV-1 RNA level was less than 50 copies per milliliter in 49 percent of the women who had received intrapartum nevirapine , as compared with 68 percent of the women who had not received intrapartum nevirapine ( P=0.03 ) . Resistance mutations to nonnucleoside reverse-transcriptase inhibitors were detectable in blood sample s obtained 10 days post partum from 32 percent of the women who had received intrapartum nevirapine ; the most frequent mutations were K103N , G190A , and Y181C . Among the women who had received intrapartum nevirapine , viral suppression was achieved at six months in 38 percent of those with resistance mutations and 52 percent of those without resistance mutations ( P=0.08 ) . An HIV-1 RNA level at or above the median of 4.53 log10 copies per milliliter before therapy and intrapartum exposure to nevirapine were independently associated with virologic failure . After six months of therapy , there was no significant difference between groups in the CD4 count ( P=0.65 ) . CONCLUSIONS Women who received intrapartum nevirapine were less likely to have virologic suppression after six months of postpartum treatment with a nevirapine-containing regimen . Our data suggest the need for strategies to maximize the benefits of both antiretroviral prophylaxis against mother-to-child transmission of HIV and antiretroviral therapy for mothers A multicenter r and omized , double blind , placebo-controlled clinical trial was conducted to evaluate the effectiveness of a short course of oral zidovudine ( ZDV ) treatment in HIV-1 infected pregnant women , starting at 38 weeks of gestation plus ZDV infusion during labor until delivery , to reduce HIV-1 vertical transmission in non-breast fed infants . One hundred and eighty two asymptomatic antiretroviral naïve HIV-1 infected pregnant women were enrolled . Each patient was r and omly allocated into either the ZDV or placebo group . The ZDV group received 250 mg ZDV orally twice a day initiated at 38 weeks ' gestation until the onset of labor . During the intrapartum period , ZDV infusion at the rate of 2 mg/kg was administered within the first hour and then continuously infused at the rate of 1 mg/kg/h until delivery . The placebo group received an identical capsule during pregnancy and normal saline infusion during labor until delivery . HIV-1 transmission was documented by nested polymerase chain reaction in infants at birth and at 1 , 3 and , 6 months of age . The estimated HIV-1 vertical transmission rate was 14.9 per cent ( 95 % CI = 11.1 to 18.7 ) and 16.3 per cent ( 95 % CI = 12.3 to 20.9 ) in ZDV and placebo group , respectively ( p > 0.05 ) . The short course ZDV in antiretroviral naïve pregnant women initiated at 38 weeks ' gestation plus intrapartum ZDV infusion without treatment in the infants was not effective to prevent HIV-1 vertical transmission BACKGROUND The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to treat human immunodeficiency virus type 1 ( HIV-1 ) infection are not clear . We compared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with treatment with the two nucleosides alone in HIV-infected adults previously treated with zidovudine . METHODS A total of 1156 patients not previously treated with lamivudine or protease inhibitors were stratified according to CD4 cell count ( 50 or fewer vs. 51 to 200 cells per cubic millimeter ) and r and omly assigned to one of two daily regimens : 600 mg of zidovudine ( or stavudine ) and 300 mg of lamivudine , or that regimen with 2400 mg of indinavir . The primary end point was the time to the development of the acquired immunodeficiency syndrome ( AIDS ) or death . RESULTS The proportion of patients whose disease progressed to AIDS or death was lower with indinavir , zidovudine , and lamivudine ( 6 percent ) than with zidovudine and lamivudine alone ( 11 percent ; estimated hazard ratio , 0.50 ; 95 percent confidence interval , 0.33 to 0.76 ; P=0.001 ) . Mortality in the two groups was 1.4 percent and 3.1 percent , respectively ( estimated hazard ratio , 0.43 ; 95 percent confidence interval , 0.19 to 0.99 ; P=0.04 ) . The effects of treatment were similar in both CD4 cell strata . The responses of CD4 cells and plasma HIV-1 RNA paralleled the clinical results . CONCLUSIONS Treatment with indinavir , zidovudine , and lamivudine as compared with zidovudine and lamivudine alone significantly slows the progression of HIV-1 disease in patients with 200 CD4 cells or fewer per cubic millimeter and prior exposure to zidovudine Despite the success of antiretroviral prophylaxis in reducing mother-to-child HIV-1 transmission , postpartum transmission through breast milk remains a problem . Antiretroviral administration to the infant during the period of breast-feeding could protect against postnatal transmission . An open-label phase 1/2 study was design ed to assess the safety and trough concentrations of nevirapine ( NVP ) given once weekly ( OW ) , twice weekly ( TW ) , or once daily ( OD ) to HIV-exposed breast-feeding infants for 24 weeks . Following maternal dosing with 200 mg NVP orally at onset of labor , breast-feeding infants were r and omized within 48 hours of birth to 1 of 3 regimens : arm 1 , NVP given OW ( 4 mg/kg from birth to 14 days , ↑ to 8 mg/kg from 15 days to 24 weeks ) , arm 2 , NVP given TW ( 4 mg/kg from birth to 14 days , ↑ to 8 mg/kg from 15 days to 24 weeks ) , and arm 3 , NVP given OD ( 2 mg/kg from birth to 14 days , ↑ to 4 mg/kg from 15 days to 24 weeks ) . Trough NVP concentrations and clinical and laboratory abnormalities were monitored . Of the 75 infants r and omized ( 26 to OW , 25 to TW , and 24 to OD dosing ) , 63 completed the 32-week follow-up visit . No severe skin , hepatic , or renal toxicity related to NVP was observed . Neutropenia occurred in 8 infants . Trough NVP levels were lower than the therapeutic target ( 100 ng/mL ) in 48 of 75 ( 64.0 % ) sample s from infants in the OW arm , 3 of 65 ( 4.6 % ) sample s in the TW arm , and 0 of 72 sample s in the OD arm . Median ( range ) trough NVP concentrations were 64 ng/mL ( range : < 25–1519 ng/mL ) with OW dosing ; 459 ( range : < 25–1386 ng/mL ) with TW dosing ; and 1348 ( range : 108–4843 ng/ml ) with OD dosing . Our data indicate that NVP prophylaxis for 6 months was safe and well tolerated in infants . OD NVP dosing result ed in all infants with trough concentration greater than the therapeutic target and maintenance of high drug concentrations . A phase 3 study is planned to assess the efficacy of OD infant NVP regimen to prevent breast-feeding HIV-1 transmission OBJECTIVE To assess the practicality and effectiveness of an Ultra-Short zidovudine regimen for prevention of perinatal HIV transmission in rural Zimbabwe . DESIGN Double-blinded placebo-controlled r and omized clinical trial . SETTING The Salvation Army Howard Hospital , a district hospital in rural Zimbabwe . SUBJECTS 222 HIV positive pregnant women presenting for antenatal care prior to 36 weeks were r and omized . Twenty nine women were lost to follow up . INTERVENTION In the Thai regimen , mothers received zidovudine ( 300 mg po bid ) from 36 weeks gestation until labour , and zidovudine ( 300 mg po q3h ) during labour , and the neonates received a placebo . In the Ultra-Short regimen , the mothers received a placebo from 36 weeks to labour , then zidovudine ( 300 mg po q3h ) in labour . The neonates received zidovudine ( 2 mg/kg po qid ) for the first three days of life . MAIN OUTCOME MEASURE Infant HIV RNA status at six weeks of life . RESULTS Results were available for 90 infants from the Thai group and 89 infants from the Ultra-Short group . Infant HIV seroconversion rates at six weeks of life were 18.9 % ( 95%CI 10.8 to 27.0 ) with the Thai regimen , and 15.7 % [ 95 % Confidence Interval ( CI ) 8.1 to 23.4 ] with the Ultra-Short regimen . The upper bound of seroconversion in the Ultra-Short group was lower than the 25 % seroconversion boundary that was specified to show equivalence . CONCLUSIONS Although the Ultra-Short regimen has equivalent efficacy to the Thai regimen , it also has many practical advantages . Ultra-Short is thus a preferable protocol BACKGROUND A substantial proportion of perinatally acquired infections with the human immunodeficiency virus type 1 ( HIV-1 ) occur at or near delivery , which suggests that obstetrical factors may have an important influence on transmission . We evaluated the relation of such factors and other variables to the perinatal transmission of HIV-1 . METHODS The Women and Infants Transmission Study is a prospect i ve , observational study of HIV-1-infected women who were enrolled during pregnancy and followed with their infants for three years after delivery . We studied obstetrical , clinical , immunologic , and virologic data on 525 women who delivered live singleton infants whose HIV-1-infection status was known as of August 31 , 1994 . RESULTS Among mothers with membranes that ruptured more than four hours before delivery , the rate of transmission of HIV-1 to the infants was 25 percent , as compared with 14 percent among mothers with membranes that ruptured four hours or less before delivery . In a multivariate analysis , the presence of ruptured membranes for more than four hours nearly doubled the risk of transmission ( odds ratio , 1.82 ; 95 percent confidence interval , 1.10 to 3.00 ; P = 0.02 ) , regardless of the mode of delivery . The other maternal factors independently associated with transmission were illicit-drug use during pregnancy ( odds ratio , 1.90 ; 95 percent confidence interval , 1.14 to 3.16 ; P = 0.01 ) , low antenatal CD4 + lymphocyte count ( < 29 percent of total lymphocytes ) ( odds ratio , 2.82 ; 1.67 to 4.76 ; P<0.001 ) , and birth weight < 2500 g ( odds ratio , 1.86 ; 1.03 to 3.34 ; P = 0.04 ) . CONCLUSIONS The risk of transmission of HIV-1 from mother to infant increases when the fetal membranes rupture more than four hours before delivery Abstract We assessed the safety of short-term antiretroviral prophylaxis to prevent mother-to-child transmission ( MTCT ) of HIV by monitoring haematological changes in children up to the age of 18 months . Babies of HIV-infected women were r and omised at birth to receive a single dose of nevirapine ( NVP ) alone or with zidovudine ( ZDV ) twice daily for a week . Based on the time of presentation to the labour ward , mothers of these babies might or might not have received intrapartum NVP . Complete blood counts were performed at birth and at 1.5 , 3 , 6 , 9 , 12 , 15 and 18 months . Babies ' HIV status was determined by HIV-1 RNA testing . A total of 1755 babies were included in the study . Age-specific mean haemoglobin levels and prevalence of anaemia ( haemoglobin < 10 g/dL ) were not significantly different in cases where only the babies received a single dose of NVP and cases where NVP was given to mother/infant pairs or additional ZDV to the baby . Among HIV-infected children compared with uninfected children , the age-specific frequency of anaemia was significantly greater , anaemia started earlier and recovery to normal levels was slower and prolonged . A reversible granulocytopenia was observed in all children between 1.5 and 3 months of age . HIV infection significantly increased the children 's risk of death . Antiretroviral prophylaxis appeared to protect against anaemia and child death . Short regimens of antiretrovirals to prevent MTCT of HIV are not associated with long-term adverse haematological changes BACKGROUND Many developing countries have not implemented the AIDS Clinical Trials Group 076 zidovudine regimen for prevention of perinatal HIV-1 transmission because of its complexity and cost . We investigated the safety and efficacy of short-course oral zidovudine administered during late pregnancy and labour . METHODS In a r and omised , double-blind , placebo-controlled trial , HIV-1-infected pregnant women at two Bangkok hospitals were r and omly assigned placebo or one zidovudine 300 mg tablet twice daily from 36 weeks ' gestation and every 3 h from onset of labour until delivery . Mothers were given infant formula and asked not to breastfeed . The main endpoint was babies ' HIV-1-infection status , tested with HIV-1-DNA PCR at birth , 2 months , and 6 months . We measured maternal plasma viral concentrations by RNA PCR . FINDINGS Between May , 1996 , and December , 1997 , 397 women were r and omised ; 393 gave birth to 395 live-born babies . Median duration of antenatal treatment was 25 days , and median number of doses during labour was three . 99 % of women took at least 90 % of scheduled antenatal doses . Adverse events were similar in the study groups . Of 392 babies with at least one PCR test , 55 tested positive : 18 in the zidovudine group and 37 in the placebo group . The estimated transmission risks were 9.4 % ( 95 % CI 5.2 - 13.5 ) on zidovudine and 18.9 % ( 13.2 - 24.2 ) on placebo ( p=0.006 ; efficacy 50.1 % [ 15.4 - 70.6 ] ) . Between enrolment and delivery , women in the zidovudine group had a mean decrease in viral load of 0.56 log . About 80 % of the treatment effect was explained by lowered maternal viral concentrations at delivery . INTERPRETATION A short course of twice-daily oral zidovudine was safe and well tolerated and , in the absence of breastfeeding , can lessen the risk for mother-to-child HIV-1 transmission by half . This regimen could prevent many HIV-1 infections during late pregnancy and labour in less-developed countries unable to implement the full 076 regimen BACKGROUND In Africa , the risk of mother-to-child transmission of HIV-1 infection is high . Short-course perinatal oral zidovudine might decrease the rate of transmission . We assessed the safety and efficacy of such a regimen among HIV-1-seropositive breastfeeding women in Abidjan , Côte d'Ivoire . METHODS From April , 1996 , to February , 1998 , all consenting , eligible HIV-1-seropositive pregnant women attending a public antenatal clinic in Abidjan were enrolled at 36 weeks ' gestation and r and omly assigned placebo or zidovudine ( 300 mg tablets ) , one tablet twice daily until the onset of labour , one tablet at onset of labour , and one tablet every 3 h until delivery . We used HIV-1-DNA PCR to test the infection status of babies at birth , 4 weeks , and 3 months . We stopped the study on Feb 18 , 1998 , when efficacy results were available from a study in Bangkok , Thail and , in which the same regimen was used in a non-breastfeeding population . FINDINGS 280 women were enrolled ( 140 in each group ) . The median duration of the prenatal drug regimen was 27 days ( range 1 - 80 ) and the median duration of labour was 7.5 h. Treatment was well tolerated with no withdrawals because of adverse events . All babies were breastfed . Among babies with known infection status at age 3 months , 30 ( 26.1 % ) of 115 babies in the placebo group and 19 ( 16.5 % ) of 115 in the zidovudine group were identified as HIV-1 infected . The estimated risk of HIV-1 transmission in the placebo and zidovudine groups were 21.7 % and 12.2 % ( p=0.05 ) at 4 weeks , and 24.9 % and 15.7 % ( p=0.07 ) at 3 months . Efficacy was 44 % ( 95 % CI -1 to 69 ) at age 4 weeks and 37 % ( -5 to 63 ) at 3 months . INTERPRETATION Short-course oral zidovudine was safe , well tolerated , and decreased mother-to-child transmission of HIV-1 at age 3 months . Substantial efforts will be needed to ensure successful widespread implementation of such a regimen Objective : To determine the safety of the zidovudine ( ZDV ) regimen utilized in the Pediatric AIDS Clinical Trial Group ( ACTG ) 076 study . Design : ACTG 076 was a r and omized , double-blind , placebo-controlled trial which demonstrated that a ZDV regimen could prevent mother-to-child HIV-1 transmission . Infants were followed through 18 months of age and women were followed through 6 months postpartum . Methods : Maternal complications , pregnancy outcomes , growth and development of the uninfected infants , and HIV-1 disease progression in the women were monitored prospect ively . Results : Maternal therapy was well tolerated . There was no serious pattern of adverse pregnancy outcomes associated with ZDV use . Amongst the ZDV-exposed infants , the only recognized toxicity was anemia within the first 6 weeks of life ; the risk for anemia was not associated with premature delivery , duration of maternal treatment , degree of maternal immunosuppression , or maternal anemia . ZDV treatment was not associated with an increased incidence of newborn structural abnormalities . At 18 months of age , uninfected infants did not differ in growth parameters or immune function . No childhood neoplasias were reported in either group . In the women , at 6 months postpartum , there were no differences in clinical , immunologic , or virologic disease progression . Conclusion : There were no identified problems that would alter current recommendations for the routine use of ZDV for the prevention of mother – child HIV-1 transmission BACKGROUND AND METHODS A placebo-controlled trial has shown that treatment with zidovudine reduces the rate at which human immunodeficiency virus type 1 ( HIV-1 ) is transmitted from mother to infant . We present data from that trial showing the number of infected infants at 18 months of age and the relation between the maternal viral load , the risk of HIV-1 transmission , and the efficacy of zidovudine treatment . Viral cultures were obtained , and HIV-1 RNA was measured by two assays in sample s of maternal blood obtained at study entry and at delivery . RESULTS In 402 mother-infant pairs , the rate of transmission of HIV-1 was 7.6 percent ( 95 percent confidence interval , 4.3 to 12.3 percent ) with zidovudine treatment and 22.6 percent ( 95 percent confidence interval , 17.0 to 29.0 percent ) with placebo ( P<0.001 ) . In the placebo group , a large viral burden at entry or delivery or a positive culture was associated with an increased risk of transmission ( the transmission rate was greater than 40 percent in the highest quartile of the RNA level ) . In both groups , transmission occurred at a wide range of maternal plasma HIV-1 RNA levels . Zidovudine reduced plasma RNA levels somewhat ( median reduction , 0.24 log ) . Zidovudine was effective regardless of the HIV-1 RNA level or the CD4 + count at entry . In the zidovudine group , however , after we adjusted for the base-line HIV-1 RNA level and CD4 + count , the reduction in viral RNA from base line to delivery was not significantly associated with the risk of transmission of HIV-1 . CONCLUSIONS A high maternal plasma concentration of virus is a risk factor for the transmission of HIV-1 from an untreated mother to her infant . The reduction in such transmission after zidovudine treatment is only partly explained by the reduction in plasma levels of viral RNA . To prevent HIV-1 transmission , initiating maternal treatment with zidovudine is recommended regardless of the plasma level of HIV-1 RNA or the CD4 + count BACKGROUND In sub-Saharan Africa , most women present late for delivery with unknown HIV status , which limits the use of intrapartum nevirapine to prevent mother-to-child transmission of HIV . We aim ed to determine whether post-exposure prophylaxis of nevirapine plus zidovudine given to babies only reduced transmission of HIV more than did a regimen of nevirapine alone . METHODS We r and omly assigned 1119 babies of Malawian women with HIV-1 who presented late ( ie , within 2 h of expected delivery ) to either nevirapine alone or nevirapine and zidovudine . Both drugs were given immediately after birth : one dose of nevirapine ( 2 mg/kg weight ) was given as a single dose ; babies in the nevirapine plus zidovudine group also received zidovudine twice daily for 1 week ( 4 mg/kg weight ) . Infant HIV infection was determined at birth and at 6 - 8 weeks . Primary outcome was HIV infection in babies at 6 - 8 weeks in those not infected at birth . Analysis was by intention to treat . FINDINGS The overall rate of mother-to-child transmission at 6 - 8 weeks was 15.3 % in 484 babies who received nevirapine and zidovudine and 20.9 % in 468 babies who received nevirapine only ( p=0.03 ) . At 6 - 8 weeks , in babies who were HIV negative at birth , 34 ( 7.7 % ) babies who had nevirapine and zidovudine and 51 ( 12.1 % ) who received nevirapine only were infected (p=0.03)-a protective efficacy of 36 % . This finding remained after controlling for maternal viral load and other factors at baseline . Adverse events were mild and of similar frequency in the two groups . INTERPRETATION Postexposure prophylaxis can offer protection against HIV infection to babies of women who missed opportunities to be counselled and tested before or during pregnancy . The nevirapine and zidovudine regimen is safe and easy to implement OBJECTIVE To determine the safety , pharmacokinetics , tolerance , antiretroviral activity , and infant HIV infection status after giving a single dose of nevirapine to HIV-1-infected pregnant women during labor and their newborns during the first week of life . DESIGN An open label phase I/II study . SETTING Tertiary care hospital , Kampala , Ug and a. PATIENTS AND INTERVENTIONS Nevirapine , 200 mg , was given as a single dose during labor to 21 HIV-1-infected pregnant Ug and an women . In cohort 1 , eight infants did not receive nevirapine whereas in cohort 2 , 13 infants received a single dose of nevirapine , 2 mg/kg , at 72 h of age . OUTCOMES The number and type of adverse events ; nevirapine concentrations in the plasma and breast milk ; maternal plasma HIV-1 RNA copy number before and up to 6 weeks after delivery ; and HIV-1 infection status of the infants were monitored . RESULTS Nevirapine was well tolerated by women and infants ; no serious adverse events that were related to nevirapine were observed . Median nevirapine concentration in the women at delivery was 1623 ng/ml ( range 238 - 2356 ng/ml ) ; median cord/maternal blood ratio of 0.75 ( 0.37 - 0.93 ) . The median half-life in women was 61.3 h ( 27 - 90 h ) and the transplacental nevirapine half-life in infants who did not receive a neonatal dose was 54 h. The median half-life after a single dose at 72 h in infants was 46.5 h. During the first week of life , the median colostrum/breast milk to maternal plasma nevirapine concentration was 60.5 % ( 25 - 122 % ) . The median nevirapine concentration in breast milk 1 week after delivery was 103 ng/ml ( 25 - 309 ng/ml ) . Plasma nevirapine concentrations were above 100 ng/ml in all infants from both cohorts tested at age 7 days . Maternal HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum , and returned to baseline by 6 weeks postpartum . Detectable plasma HIV-1 RNA was observed in one out of 22 ( 4.5 % ) infants at birth ; three out of 21 ( 14 % ) at 6 weeks ; and four out of 21 ( 19 % ) at 6 months of age . CONCLUSION The administration of a single dose of nevirapine to women during labor and to their newborns at 72 h was well tolerated and showed potent antiretroviral activity in the women at 1 week after dosing without rebound above baseline 6 weeks after a single dose . The nevirapine concentration was maintained above the target of 100 ng/ml in infants at age 7 days , even in those infants not receiving a neonatal dose . This regimen has promise as prophylaxis against intrapartum and early breast milk transmission in a breastfeeding population BACKGROUND In 1999 , we reported safety and efficacy data for short-course nevirapine from a Ug and an perinatal HIV-1 prevention trial when 496 babies were followed up to age 14 - 16 weeks . Safety and efficacy data are now presented for all babies followed up to 18 months of age . METHODS From November , 1997 , to April , 1999 , HIV-1 infected pregnant women in Kampala , Ug and a , were r and omly assigned nevirapine ( 200 mg at labour onset and 2mg/kg for babies within 72 h of birth ; regimen A ) or zidovudine ( 600 mg orally at labour onset and 300 mg every 3 h until delivery , and 4 mg/kg orally twice daily for babies for 7 days , regimenB ) . Infant HIV-1 testing was done at birth , age 6 - 8 and 14 - 16 weeks , and age 12 months by HIV-1 RNA PCR , and by HIV-1 antibody at 18 months . HIV-1 transmission and HIV-1-free survival were assessed using Kaplan-Meier analysis . We recorded adverse experiences through 6 - 8 weeks postpartum for mothers , and 18 months for babies . Efficacy analyses were by intention to treat . FINDINGS We enrolled 645 mothers to the study : 313 were assigned regimen A , 313 regimen B , and 19 placebo . Eight mothers were lost to follow-up before delivery . 99 % of babies were breastfed ( median duration 9 months ) . Estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were 10.3 % and 8.1 % at birth ( p=0.35 ) ; 20.0 % and 11.8 % by age 6 - 8 weeks ( p=0.0063 ) ; 22.1 % and 13.5 % by age 14 - 16 weeks ( p=0.0064 ) ; and 25.8 % and 15.7 % by age 18 months ( p=0.0023 ) . Nevirapine was associated with a 41 % ( 95 % CI 16 - 59 ) reduction in relative risk of transmission through to age 18 months . Both regimens were well-tolerated with few serious side-effects . INTERPRETATION Intrapartum/neonatal nevirapine significantly lowered HIV-1 transmission risk in a breastfeeding population in Ug and a compared with a short intrapartum/neonatal zidovudine regimen . The absolute 8.2 % reduction in transmission at 6 - 8 weeks was sustained at age 18 months ( 10.1 % [ 95 % CI 3.5 - 16.6 ] ) . This simple , inexpensive , well-tolerated regimen has the potential to significantly decrease HIV-1 perinatal transmission in less-developed countries Objective To assess the 24 month efficacy of a maternal short-course zidovudine regimen to prevent mother-to-child transmission ( MTCT ) of HIV-1 in a breastfeeding population in West Africa . Methods Data were pooled from two clinical trials : DITRAME-ANRS049a conducted in Abidjan , Côte d'Ivoire and Bobo-Dioulasso , Burkina-Faso and RETRO-CI , conducted in Abidjan . Between September 1995 and February 1998 , consenting HIV-1-seropositive women were r and omly assigned to receive zidovudine ( 300 mg ) or placebo : one tablet twice daily from 36–38 weeks ’ gestation until delivery , then in DITRAME only , for 7 more days . Paediatric HIV-1 infection was defined as a positive HIV-1 polymerase chain reaction , or if aged ⩾ 15 months , a positive HIV-1 serology . Cumulative risks ( CR ) of infection were estimated using a competing risk approach with weaning as a competing event . Results Among 662 live-born children , 641 had at least one HIV-1 test . All but 12 children were breastfed . At 24 months , overall CR of MTCT were 0.225 in the zidovudine and 0.302 in the placebo group , a 26 % significant reduction . Among children born to women with CD4 cell counts < 500/ml at enrolment , CR of MTCT were similar , 0.396 in the zidovudine and 0.413 in the placebo group . Among children born to women with CD4 cell counts ⩾ 500/ml , CR of MTCT were 0.091 in the zidovudine and 0.220 in the placebo group , a significant 59 % reduction . Conclusion A maternal short-course zidovudine regimen reduces MTCT of HIV-1 at age 24 months , despite prolonged breastfeeding . However , efficacy was observed only among women with CD4 cell counts ⩾ 500/ml . New interventions should be considered to prevent MTCT , especially for African women with advanced HIV-1 immunodeficiency Postnatal transmission of HIV through breast milk complicates both the design of effective interventions to prevent mother-to-child transmission of HIV ( PMTCT ) and their evaluation . Estimated long-term efficacy in five African trials ( four with peri-partum antiretrovirals and one with artificial feeding ) varied from 25 to 50 per cent . This variation may be due , at least in part , to differences in analytical methodology . To facilitate direct comparison between trials , a method ological consensus approach to the analysis and presentation of the results of PMTCT trials was developed . The initial methodology used and results presented from African trials with available long-term efficacy data were review ed during a workshop in Bordeaux , France , in September 2000 . A consensus approach for evaluating efficacy applicable across PMTCT studies was developed . There are four typical situations defined by duration of follow-up ( short versus long ) , and the available demographic ( vital status ) and biological data ( single versus repeat HIV testing ) . Efficacy can be assessed from the risk of infection directly or from HIV-free survival by combining infection and death as a single endpoint . Studies should report results in a st and ardized format including infection , weaning , mortality and loss to follow-up . New statistical methods that account for the unknown date when a child would first test positive for HIV , for weaning as a competing risk for HIV infection , and for increased risk of death among HIV-infected children should be used in analysing data from PMTCT studies with repeat HIV testing . All estimates should be reported with confidence intervals . This st and ardized methodology that allows direct comparison between studies is now being applied to four r and omized clinical trials Objective To examine the emergence and fading of NVP resistance ( NVPR ) mutations in HIV-1-infected Ug and an women and infants who received single dose NVP to prevent HIV-1 vertical transmission . Design We examined NVPR in women and infants who received NVP in the HIVNET 012 clinical trial , including 41 out of 48 women with infected infants , 70 r and omly-selected women with uninfected infants , and 33 out of 49 infected infants . Methods Plasma HIV-1 was analyzed using the Applied Biosystems ViroSeq HIV-1 Genotyping System . Results NVPR mutations were detected in 21 out of 111 ( 19 % ) women tested 6–8 weeks after delivery . The rate of NVPR was similar among women whose infants were or were not HIV-1 infected . K103N was the most common mutation detected . NVPR mutations faded from detection within 12–24 months in all 11 evaluable women . High baseline viral load and low baseline CD4 cell count were associated with development of NVPR . NVPR mutations were detected in 11 out of 24 ( 46 % ) evaluable infants who were infected by 6–8 weeks of age . The most common NVPR mutation detected in infants was Y181C . Those mutations faded from detection by 12 months of age in all seven evaluable infants . Of nine evaluable infants with late HIV-1 infection , only one had evidence of NVPR . Conclusions NVPR was detected more frequently in infants than women following NVP prophylaxis , and different patterns of NVPR mutations were detected in women versus infants . NVPR was detected infrequently in infants with late HIV-1 infection . NVP-resistant HIV-1 faded from detection in women and infants over time The efficacy of a short-term regimen of zidovudine ( ZDV ) in preventing perinatal HIV transmission was investigated in a r and omized case-placebo study conducted at two teaching hospitals in Bangkok Thail and in 1996 - 97 . The 198 women in the intervention group were given 300 mg of ZDV orally twice a day from 38 weeks of gestation until the onset of labor and 300 mg every 3 hours thereafter until delivery . Another 199 women received a placebo . Infants in both groups were fed formula rather than breast milk . At 6 months of age 52 children ( 17 from the ZDV group and 35 in the placebo group ) were HIV-positive ; all HIV infections were evident at 2 months of age . The HIV transmission risk was 9.2 % ( 95 % CI 5.0 - 13.5 % ) in the ZDV group and 18.6 % in the placebo group ( 95 % CI 13.0 - 24.0 % ) signifying a 51 % decrease in risk . The ZDV regimen used in this study is more feasible for implementation in developing country setting s than the one currently used in the US ( associated with a 66 % reduction in HIV transmission ) : it costs US$ 50 starts later in pregnancy involves less frequent dosing and oral dosing during labor and does not involve infant treatment . On the basis of these findings ministries of health and donor agencies are urged to develop strategies to increase access to prenatal HIV testing and ZDV treatment for HIV-infected pregnant women in re source -poor setting s. Further evaluation is needed of the effect of breast feeding on the efficacy of this regimen BACKGROUND The optimal duration of zidovudine administration to prevent perinatal transmission of human immunodeficiency virus type 1 ( HIV-1 ) should be determined to facilitate its use in areas where re sources are limited . METHODS We conducted a r and omized , double-blind equivalence trial of zidovudine starting in the mother at 28 weeks ' gestation , with 6 weeks of treatment in the infant ( the long-long regimen ) , which is similar to protocol 076 ; zidovudine starting at 35 weeks ' gestation , with 3 days of treatment in the infant ( the short-short regimen ) ; a long-short regimen ; and a short-long regimen . The mothers received zidovudine orally during labor . The infants were fed formula and were tested for HIV DNA at 1 , 45 , 120 , and 180 days . After the first interim analysis , the short-short regimen was stopped . RESULTS A total of 1437 women were enrolled . At the first interim analysis , the rates of HIV transmission were 4.1 percent for the long-long regimen and 10.5 percent for the short-short regimen ( P=0.004 ) . For the entire study period , the transmission rates were 6.5 percent ( 95 percent confidence interval , 4.1 to 8.9 percent ) for the long-long regimen , 4.7 percent ( 95 percent confidence interval , 2.4 to 7.0 percent ) for the long-short regimen , and 8.6 percent ( 95 percent confidence interval , 5.6 to 11.6 percent ) for the short-long regimen . The rate of in utero transmission was significantly higher with the two regimens with shorter maternal treatment ( 5.1 percent ) than with the two with longer maternal treatment ( 1.6 percent ) . CONCLUSIONS The short-short zidovudine regimen is inferior to the long-long regimen and leads to a higher rate of perinatal HIV transmission . The long-short , short-long , and long-long regimens had equivalent efficacy . However , the higher rate of in utero transmission with the short-long regimen suggests that longer treatment of the infant can not substitute for longer treatment of the mother BACKGROUND Zidovudine reduces the rate of vertical transmission of HIV in non-breastfed population s. We assessed the acceptability , tolerance , and 6-month efficacy of a short regimen of oral zidovudine in African population s practising breastfeeding . METHODS A r and omised double-blind placebo-controlled trial was carried out in public clinics of Abidjan , Côte d'Ivoire , and Bobo-Dioulasso , Burkina Faso . Eligible participants were women aged 18 years or older , who had confirmed HIV-1 infection and pregnancy of 36 - 38 weeks duration , and who gave written informed consent . Exclusion criteria were severe anaemia , neutropenia , abnormal liver function , and sickle-cell disease . Women were r and omly assigned zidovudine ( n=214 ; 300 mg twice daily until labour , 600 mg at beginning of labour , and 300 mg twice daily for 7 days post partum ) or matching placebo ( n=217 ) . The primary outcome was the diagnosis of HIV-1 infection in the infant on the basis of sequential DNA PCR tests at days 1 - 8 , 45 , 90 , and 180 . We compared the probability of infection at a given age in the two groups . Analyses were by intention to treat . FINDINGS Women were enrolled between September , 1995 , and February , 1998 , when enrolment to the placebo group was stopped . Analysis was based on 421 women and 400 lifeborn infants . Baseline demographic , clinical , and laboratory characteristics were similar in the two groups . The Kaplan-Meier probability of HIV infection in the infant at 6 months was 18.0 % in the zidovudine group ( n=192 ) and 27.5 % in the placebo group ( n=197 ; relative efficacy 0.38 [ 95 % CI 0.05 - 0.60 ] ; p=0.027 ) . Adjustment for centre , period of recruitment , mode of delivery , maternal CD4-cell count , duration of labour , prolonged rupture of membranes , and duration of breastfeeding did not change the treatment effect . The proportions of women taking more than 80 % of the planned maximum dose were 75 % before delivery , 81 % during labour , and 83 % post partum , without statistical difference between the groups . No major adverse biological or clinical event was reported in excess among women and children of the zidovudine group . INTERPRETATION A short course of oral zidovudine given during the peripartum period is well accepted and well tolerated , and provides a 38 % reduction in early vertical transmission of HIV-1 infection despite breastfeeding |
2,234 | 30,518,253 | The acute ingestion of a moderate dose of caffeine had a small but significant positive effect on several aspects related to physical performance in team sports | The aim of this investigation was to perform a systematic review and meta- analysis to determine the efficacy of the acute ingestion of caffeine ( from 3 to 6 mg/kg ) to increase performance on variables related to team sports . | Previous investigations have determined that some individuals have minimal or even ergolytic performance effects after caffeine ingestion . The aim of this study was to analyze the influence of the genetic variations of the CYP1A2 gene on the performance enhancement effects of ingesting a moderate dose of caffeine . In a double-blind r and omized experimental design , 21 healthy active participants ( 29.3 ± 7.7 years ) ingested 3 mg of caffeine per kg of body mass or a placebo in testing sessions separated by one week . Performance in the 30 s Wingate test , visual attention , and side effects were evaluated . DNA was obtained from whole blood sample s and the CYP1A2 polymorphism was analyzed ( rs762551 ) . We obtained two groups : AA homozygotes ( n = 5 ) and C-allele carriers ( n = 16 ) . Caffeine ingestion increased peak power ( 682 ± 140 vs. 667 ± 137 W ; p = 0.008 ) and mean power during the Wingate test ( 527 ± 111 vs. 518 ± 111 W ; p < 0.001 ) with no differences between AA homozygotes and C-allele carriers ( p > 0.05 ) . Reaction times were similar between caffeine and placebo conditions ( 276 ± 31 vs. 269 ± 71 milliseconds ; p = 0.681 ) with no differences between AA homozygotes and C-allele carriers . However , 31.3 % of the C-allele carriers reported increased nervousness after caffeine ingestion , while none of the AA homozygotes perceived this side effect . Genetic variations of the CYP1A2 polymorphism did not affect the ergogenic effects and drawbacks derived from the ingestion of a moderate dose of caffeine INTRODUCTION Caffeine enhances performance of single bouts of endurance exercise , but its effects on repeated bouts typical of those in high-intensity team sports are unclear . PURPOSE To investigate effects of caffeine in a performance test simulating physical and skill dem and s of a rugby union game . METHODS The study was a double-blind , r and omized , crossover design in which nine competitive male rugby players ingested either caffeine ( 6 mg.kg(-1 ) body mass ) or placebo ( dextrose ) 70 min before performing a rugby test . Each test consisted of seven circuits in each of two 40-min halves with a 10-min half-time rest . Each circuit included stations for measurement of sprint time ( two straight-line and three agility sprints ) , power generation in two consecutive drives , and accuracy for passing balls rapidly . Interstitial fluid was sample d transdermally by electrosonophoresis before ingestion of caffeine or placebo and then before testing , at half-time , and immediately after testing ; sample s were assayed chromatographically for caffeine and epinephrine concentrations . RESULTS The effects of caffeine on mean performance ( + /-90 % confidence limits ) over all 14 circuits were : sprint speeds , 0.5 % ( + /-1.7 % ) through 2.9 % ( + /-1.3 % ) ; first-drive power , 5.0 % ( + /-2.5 % ) ; second-drive power , -1.2 % ( + /-6.8 % ) ; and passing accuracy , 9.6 % ( + /-6.1 % ) . The enhancements were mediated partly through a reduction of fatigue that developed throughout the test and partly by enhanced performance for some measures from the first circuit . Caffeine produced a 51 % ( + /-11 % ) increase in mean epinephrine concentration ; correlations between individual changes in epinephrine concentration and changes in performance were mostly unclear , but there were some strong positive correlations with sprint speeds and a strong negative correlation with passing accuracy . CONCLUSION Caffeine is likely to produce substantial enhancement of several aspects of high-intensity team-sport performance PURPOSE The objective of this study is to determine the effects of a caffeine-containing energy drink on female volleyball players ' performance . METHODS Thirteen elite female volleyball players ingested 3 mg·kg of caffeine with an energy drink or the same drink without caffeine ( placebo drink ) in a double-blind and r and omized study . Then , participants performed the following : st and ing spike , jumping spike , spike jump , blocking jump , squat jump , countermovement jump , manual dynamometry , and the agility t-test . A simulated volleyball game was played , videotaped , and notated afterward . RESULTS In comparison to the placebo drink , the ingestion of the caffeinated energy drink increased the ball velocity in the st and ing spike ( 19.2 ± 2.1 vs 19.7 ± 1.9 m·s , P = 0.023 ) and in the jumping spike ( 17.9 ± 2.2 vs 18.8 ± 2.2 m·s , P = 0.038 ) and the jump height in the squat jump ( 28.1 ± 3.2 vs 29.4 ± 3.6 cm , P = 0.028 ) , countermovement jump ( 32.0 ± 4.6 vs 33.1 ± 4.5 cm , P = 0.018 ) , spike jump ( 43.3 ± 4.7 vs 44.4 ± 5.0 cm , P = 0.025 ) , and block jump ( 35.2 ± 5.1 vs 36.1 ± 5.1 cm , P = 0.044 ) . Furthermore , the caffeinated energy drink decreased the time needed to complete the agility t-test ( 11.1 ± 0.5 vs 10.9 ± 0.3 s , P = 0.036 ) . During the game , the volleyball actions categorized as successful were more frequent with the caffeinated energy drink ( 34 % ± 9 % vs 45 % ± 9 % , P < 0.001 ) , whereas imprecise actions decreased ( 28 % ± 7 % vs 14 % ± 9 % , P < 0.001 ) when compared with the placebo drink . CONCLUSION Commercially available energy drinks can significantly improve physical performance in female volleyball players . Increased physical performance led to improved accuracy during an actual volleyball match The purpose of the present study was to examine the duration of caffeine 's ergogenic effect and whether it differs between users and nonusers of the drug . Twenty-one subjects ( 13 caffeine users and 8 nonusers ) completed six r and omized exercise rides to exhaustion at 80 % of maximal oxygen consumption after ingesting either a placebo or 5 mg/kg of caffeine . Exercise to exhaustion was completed once per week at either 1 , 3 , or 6 h after placebo or drug ingestion . Exercise time to exhaustion differed between users and nonusers with the ergogenic effect being greater and lasting longer in nonusers . For the nonusers , exercise times 1 , 3 , and 6 h after caffeine ingestion were 32.7 + /- 8.4 , 32.1 + /- 8.6 , and 31.7 + /- 12.0 min , respectively , and these values were each significantly greater than the corresponding placebo values of 24.2 + /- 6.4 , 25.8 + /- 9.0 , and 23.2 + /- 7.1 min . For caffeine users , exercise times 1 , 3 , and 6 h after caffeine ingestion were 27.4 + /- 7.2 , 28.1 + /- 7.8 , and 24.5 + /- 7.6 min , respectively . Only exercise times 1 and 3 h after drug ingestion were significantly greater than the respective placebo trials of 23.3 + /- 6.5 , 23.2 + /- 7.1 , and 23.5 + /- 5.7 min . In conclusion , both the duration and magnitude of the ergogenic effect that followed a 5 mg/kg dose of caffeine were greater in the nonusers compared with the users PURPOSE The purpose of this study was to determine the oral dose of caffeine needed to increase muscle force and power output during all-out single multijoint movements . METHODS Thirteen resistance-trained men underwent a battery of muscle strength and power tests in a r and omized , double-blind , crossover design , under four different conditions : ( a ) placebo ingestion ( PLAC ) or with caffeine ingestion at doses of ( b ) 3 mg · kg(-1 ) body weight ( CAFF 3 mg ) , ( c ) 6 mg · kg(-1 ) ( CAFF 6 mg ) , and ( d ) 9 mg · kg(-1 ) ( CAFF 9 mg ) . The muscle strength and power tests consisted in the measurement of bar displacement velocity and muscle power output during free-weight full-squat ( SQ ) and bench press ( BP ) exercises against four incremental loads ( 25 % , 50 % , 75 % , and 90 % one-repetition maximum [ 1RM ] ) . Cycling peak power output was measured using a 4-s inertial load test . Caffeine side effects were evaluated at the end of each trial and 24 h later . RESULTS Mean propulsive velocity at light loads ( 25%-50 % 1RM ) increased significantly above PLAC for all caffeine doses ( 5.4%-8.5 % , P = 0.039 - 0.003 ) . At the medium load ( 75 % 1RM ) , CAFF 3 mg did not improve SQ or BP muscle power or BP velocity . CAFF 9 mg was needed to enhance BP velocity and SQ power at the heaviest load ( 90 % 1RM ) and cycling peak power output ( 6.8%-11.7 % , P = 0.03 - 0.05 ) . The CAFF 9 mg trial drastically increased the frequency of the adverse side effects ( 15%-62 % ) . CONCLUSIONS The ergogenic dose of caffeine required to enhance neuromuscular performance during a single all-out contraction depends on the magnitude of load used . A dose of 3 mg · kg(-1 ) is enough to improve high-velocity muscle actions against low loads , whereas a higher caffeine dose ( 9 mg · kg(-1 ) ) is necessary against high loads , despite the appearance of adverse side effects PURPOSE The purpose of this investigation was to assess the acute effects of caffeine ingestion on short-term , high-intensity exercise ( ST ) after a period of oral creatine supplementation and caffeine abstinence . METHODS Fourteen trained male subjects performed treadmill running to volitional exhaustion ( T(lim ) ) at an exercise intensity equivalent to 125 % VO(2max ) . Three trials were performed , one before 6 d of creatine loading ( 0.3 g x kg x d(-1 ) baseline ) , and two further trials after the loading period . One hour before the postloading trials , caffeine ( 5 mg x kg(-1 ) ) or placebo was orally ingested in a cross-over , double-blind fashion . Four measurements of rating of perceived exertion were taken , one every 30 s , during the first 120 s of the exercise . Blood sample s were assayed for lactate , glucose , potassium , and catecholamines , immediately before and after exercise . RESULTS Body mass increased ( P < 0.05 ) over the creatine supplementation period , and this increase was maintained for both caffeine and placebo trials . There was no increase in the maximal accumulated oxygen deficit between trials ; however , total VO(2 ) was significantly increased in the caffeine trial in comparison with the placebo trial ( 13.35 + /- 3.89 L vs 11.67 + /- 3.61 L ) . In addition , caffeine T(lim ) ( 222.1 + /- 48.9 s ) was significantly greater ( P < 0.05 ) than both baseline ( 200.8 + /- 33.4 s ) and placebo ( 198.3 + /- 45.4 s ) T(lim ) . RPE was also lower at 90 s in the caffeine treatment ( 13.8 + /- 1.8 RPE points ) in comparison with baseline ( 14.6 + /- 1.9 RPE points ) . CONCLUSION As indicated by a greater T(lim ) , acute caffeine ingestion was found to be ergogenic after 6-d of creatine supplementation and caffeine abstinence Purpose Many studies have examined the effect of caffeine on exercise performance , but findings have not always been consistent . The objective of this study was to determine whether variation in the CYP1A2 gene , which affects caffeine metabolism , modifies the ergogenic effects of caffeine in a 10-km cycling time trial . Methods Competitive male athletes ( n = 101 ; age = 25 ± 4 yr ) completed the time trial under three conditions : 0 , 2 , or 4 mg of caffeine per kilogram body mass , using a split-plot r and omized , double-blinded , placebo-controlled design . DNA was isolated from saliva and genotyped for the −163A > C polymorphism in the CYP1A2 gene ( rs762551 ) . Results Overall , 4 mg·kg−1 caffeine decreased cycling time by 3 % ( mean ± SEM ) versus placebo ( 17.6 ± 0.1 vs 18.1 ± 0.1 min , P = 0.01 ) . However , a significant ( P < 0.0001 ) caffeine – gene interaction was observed . Among those with the AA genotype , cycling time decreased by 4.8 % at 2 mg·kg−1 ( 17.0 ± 0.3 vs 17.8 ± 0.4 min , P = 0.0005 ) and by 6.8 % at 4 mg·kg−1 ( 16.6 ± 0.3 vs 17.8 ± 0.4 min , P < 0.0001 ) . In those with the CC genotype , 4 mg·kg−1 increased cycling time by 13.7 % versus placebo ( 20.8 ± 0.8 vs 18.3 ± 0.5 min , P = 0.04 ) . No effects were observed among those with the AC genotype . Conclusion Our findings show that both 2 and 4 mg·kg−1 caffeine improve 10-km cycling time , but only in those with the AA genotype . Caffeine had no effect in those with the AC genotype and diminished performance at 4 mg·kg−1 in those with the CC genotype . CYP1A2 genotype should be considered when deciding whether an athlete should use caffeine for enhancing endurance performance PURPOSE To examine the effects of a moderate dose of caffeine in elite male volleyball players on countermovement-jump ( CMJ ) performance , as well as temporal concentric- and eccentric-phase effects . METHODS Ten elite male volleyball players took part in 2 experimental days via a r and omized crossover trial 1 wk apart in which they ingested either 5 mg/kg of caffeine or a placebo in double-blind fashion . Heart rate and blood pressure were measured at rest and 60 min postingestion . Afterward , subjects also performed 3 CMJ trials 60 min postingestion , of which the average was used for further analysis . They filled out a question naire on possible side effects 24 h posttrial . RESULTS Caffeine intake , compared with placebo , increased CMJ peak concentric force ( 6.5 % ± 6.4 % ; P = .01 ) , peak power ( 16.2 % ± 8.3 % ; P < .01 ) , flight time ( 5.3 % ± 3.4 % ; P < .01 ) , velocity at peak power ( 10.6 % ± 8.0 % ; P < .01 ) , peak displacement ( 10.8 % ± 6.5 % ; P < .01 ) , peak velocity ( 12.6 % ± 7.4 % ; P < .01 ) , peak acceleration ( 13.5 % ± 8.5 % ; P < .01 ) , and the force developed at peak power ( 6.0 % ± 4.0 % ; P < .01 ) and reduced the time between peak power and peak force ( 16.7 % ± 21.6 % , P = .04 ) . Caffeine increased diastolic blood pressure by 13.0 % ± 8.9 % ( P < .05 ) , whereas no adverse side effects were found . CONCLUSIONS The ingestion of 5 mg/kg of anhydrous caffeine improves overall CMJ performance without inducing side effects Aim The purpose of this study was to examine the effect of CYP1A2 -163C > A polymorphism on the ergogenic effects of caffeine supplementation during a resistance exercise ( RE ) session . Methods In a r and omized , double-blind , placebo (PL)-controlled , crossover study , 30 resistance-trained men took part in two RE sessions ( three sets to failure at 85 % of one repetition maximum , 2-min rest between sets ) , including bench press ( BP ) , leg press ( LP ) , seated cable row , and shoulder press ( SP ) following caffeine ( CAF ) ( 6 mg kg−1 ) or PL ( 6 mg kg−1 of maltodextrin ) ingestion 1 h prior to the trial . The number of repetitions was recorded after each set , along with calculation of total number of repetitions for each exercise . Genomic DNA was isolated from the whole blood sample s for analyzing the CYP1A2 -163C > A polymorphism through amplification refractory mutation system – polymerase chain reaction ( ARMS – PCR ) . Subjects were classified as either AA ( n = 14 ) or AC/CC genotypes ( n = 16 ) . Results The two-way ANOVA with repeated measures revealed differences between AAs and AC/CCs under CAF conditions for repetitions performed in sets 1 , 2 , and 3 of BP ( F(1 , 28 ) = 14.84 , P = 0.001 , ƞ2 = 0.34 ) , LP ( F(1 , 28 ) = 8.92 , P = 0.006 , ƞ2 = 0.24 ) , SR ( F(1 , 28 ) = 17.38 , P = 0.0001 , ƞ2 = 0.38 ) , and SP ( F(1 , 28 ) = 3.76 , P = 0.063 , ƞ2 = 0.11 ) . CAF also increased the total number of repetitions performed for all three sets in AAs versus AC/CCs for BP ( F(1 , 28 ) = 8.72 , P = 0.006 , ƞ2 = 0.23 ) , LP ( F(1 , 28 ) = 4.67 , P = 0.03 , ƞ2 = 0.14 ) , SR ( F(1 , 28 ) = 5.54 , P = 0.02 , ƞ2 = 0.16 ) , and SP ( F(1 , 28 ) = 3.89 , P = 0.058 , ƞ2 = 0.12 ) in athletes who were homozygous carriers of the A allele , compared to the C allele carriers . Therefore , AA homozygotes were able to carry out a greater total volume of RE work under CAF but not PL conditions , compared to the C allele carriers . Conclusion In conclusion , acute ingestion of CAF significantly enhanced RE performance in resistance-trained men who were homozygous for the A allele , but not for C allele carriers . Further studies are needed to replicate the potential role of the CYP1A2 -163C > A polymorphism on the ergogenic effects of CAF in other modes of exercise and in other population The purpose of this study was to determine whether caffeinated gum influenced performance in a battery of soccer-specific tests used in the assessment of performance in soccer players . In a double-blind , r and omized , crossover design , 10 male university-st and ard soccer players ( age : 19 ± 1 years , stature : 1.80 ± 0.10 m , body mass : 75.5 ± 4.8 kg ) masticated a caffeinated ( 200 mg ; caffeine ) or control ( 0 mg ; placebo ) gum on two separate occasions . After a st and ardized warm-up , gum was chewed for 5 min and subsequently expectorated 5 min before players performed a maximal countermovement jump , a 20-m sprint test , and the Yo-Yo Intermittent Recovery Test Level 1 . Performance on 20-m sprints was not different between trials ( caffeine : 3.2 ± 0.3 s , placebo : 3.1 ± 0.3 s ; p = .567 ; small effect size : d = 0.33 ) , but caffeine did allow players to cover 2.0 % more distance during Yo-Yo Intermittent Recovery Test Level 1 ( caffeine : 1,754 ± 156 m , placebo : 1,719 ± 139 m ; p = .016 ; small effect size : d = 0.24 ) and increase maximal countermovement jump height by 2.2 % ( caffeine : 47.1 ± 3.4 cm , placebo : 46.1 ± 3.2 cm ; p = .008 ; small effect size : d = 0.30 ) . Performance on selected physical tests ( Yo-Yo Intermittent Recovery Test Level 1 and countermovement jump ) was improved by the chewing of caffeinated gum in the immediate period before testing in university-st and ard soccer players , but the sizes of such effects were small . Such findings may have implication s for the recommendations made to soccer players about to engage with subsequent exercise performance The aim of this study was to determine the effect of caffeine intake on overall basketball performance in experienced players . A double-blind , placebo-controlled , r and omized experimental design was used for this investigation . In two different sessions separated by one week , 20 experienced basketball players ingested 3 mg of caffeine/kg of body mass or a placebo . After 60 min , participants performed 10 repetitions of the following sequence : Abalakov jump , Change-of-Direction and Acceleration Test ( CODAT ) and two free throws . Later , heart rate , body impacts and game statistics were recorded during a 20-min simulated basketball game . In comparison to the placebo , the ingestion of caffeine increased mean jump height ( 37.3 ± 6.8 vs. 38.2 ± 7.4 cm ; p = 0.012 ) , but did not change mean time in the CODAT test or accuracy in free throws . During the simulated game , caffeine increased the number of body impacts ( 396 ± 43 vs. 410 ± 41 impacts/min ; p < 0.001 ) without modifying mean or peak heart rate . Caffeine also increased the performance index rating ( 7.2 ± 8.6 vs. 10.6 ± 7.1 ; p = 0.037 ) during the game . Nevertheless , players showed a higher prevalence of insomnia ( 19.0 vs. 54.4 % ; p = 0.041 ) after the game . Three mg of caffeine per kg of body mass could be an effective ergogenic substance to increase physical performance and overall success in experienced basketball players The effects of acute ingestion of caffeine on short- duration high-intensity performance are equivocal , while studies of novel modes of delivery and the efficacy of low doses of caffeine are warranted . The aims of the present study were to investigate the effect of acute ingestion of caffeinated chewing gum on repeated sprint performance ( RSP ) in team sport athletes , and whether habitual caffeine consumption alters the ergogenic effect , if any , on RSP . A total of 18 male team sport athletes undertook four RSP trials using a 40-m maximum shuttle run test , which incorporates 10 × 40-m sprints with 30 s between the start of each sprint . Each participant completed two familiarization sessions , followed by caffeine ( CAF ; caffeinated chewing gum ; 200 mg caffeine ) and placebo ( PLA ; noncaffeinated chewing gum ) trials in a r and omized , double-blind manner . RSP , assessed by sprint performance decrement ( % ) , did not differ ( p = .209 ; effect size = 0.16 ; N = 18 ) between CAF ( 5.00 ± 2.84 % ) and PLA ( 5.43 ± 2.68 % ) . Secondary analysis revealed that low habitual caffeine consumers ( < 40 mg/day , n = 10 ) experienced an attenuation of sprint performance decrement during CAF relative to PLA ( 5.53 ± 3.12 % vs. 6.53 ± 2.91 % , respectively ; p = .049 ; effect size = 0.33 ) ; an effect not observed in moderate/high habitual caffeine consumers ( > 130 mg/day , n = 6 ; 3.98 ± 2.57 % vs. 3.80 ± 1.79 % , respectively ; p = .684 ; effect size = 0.08 ) . The data suggest that a low dose of caffeine in the form of caffeinated chewing gum attenuates the sprint performance decrement during RSP by team sport athletes with low , but not moderate-to-high , habitual consumption of caffeine UNLABELLED Studies provide equivocal results regarding the ergogenic properties of caffeine during high-intensity exercise . PURPOSE The primary aim of this study was to examine the effects of two doses of caffeine on peak/average torque , power output , and total work of the knee extensors and flexors during two bouts of high-intensity exercise . METHODS Fifteen active men ( mean age = 26.4 ± 3.9 yr and body mass = 82.7 ± 2.9 kg ) initially completed a familiarization bout on the isokinetic dynamometer , followed by three subsequent trials separated by at least 48 h. Exercise consisted of two bouts of 40 repetitions of maximal knee extension and flexion of the dominant leg at a contraction velocity equal to 180 ° ·s . Before each trial , subjects abstained from caffeine intake and intense exercise for 48 h. Treatment order ( 5 and 2 mg·kg of anhydrous caffeine or placebo ) was r and omly assigned to subjects using a single-blind , r and omized , counterbalanced , crossover design . A 3 ( treatment ) × 2 ( sets ) ANOVA with repeated measures was used to detect differences in performance across treatment and time . RESULTS Compared with placebo , caffeine significantly ( P < 0.05 ) enhanced peak knee flexion torque , knee extension/flexion total work , and knee extension/flexion power in bout 1 with no effect in bout 2 . Only the 5-mg·kg dose of caffeine improved performance , with the magnitude of performance improvement ranging from 5 % to 8 % . CONCLUSIONS Data suggest that a relatively high ( 5-mg·kg body weight ) but not low ( 2-mg·kg body weight ) caffeine dose is ergogenic for maximal knee extension/flexion exercise PURPOSE The effect of caffeine ingestion on sprint performance is unclear . We have therefore investigated its effect on performance in a test that simulates the repeated sprints of team sports . METHODS In a r and omized double-blind crossover experiment , 16 male team-sport athletes ingested either caffeine ( 6 mg.kg-1 of body mass ) or a placebo 60 min before performing a repeated 20-m sprint test . The test consisted of 10 sprints , each performed within 10 s and followed by rest for the remainder of each 10 s. The caffeine and placebo trials followed a familiarization trial , and the time between consecutive trials was 2 - 3 d. To allow estimation of variation in treatment effects between individuals , nine subjects performed three more trials without a supplement 7 - 14 d later . We estimated the smallest worthwhile effect on sprint time in a team sport to be approximately 0.8 % . RESULTS Mean time to complete 10 sprints increased by 0.1 % ( 95 % likely range -1.5 to 1.7 % ) with caffeine ingestion relative to placebo . Individual variation in this effect was a st and ard deviation of 0.7 % ( -2.7 to 2.9 % ) . Time to complete the 10th sprint was 14.4 % longer than the first ; caffeine increased this time by 0.7 % ( -1.8 to 3.2 % ) relative to placebo , and individual variation in this effect was 2.4 % ( -3.4 to 4.9 % ) . CONCLUSION The observed effect of caffeine ingestion on mean sprint performance and fatigue over 10 sprints was negligible . The true effect on mean performance could be small at most , although the true effects on fatigue and on the performance of individuals could be somewhat larger . Pending confirmatory research , team-sport athletes should not expect caffeine to enhance sprint performance Caffeine is the neuroactive agent in coffee and tea and is a broadly consumed stimulant . It is a nonselective antagonist of the neuromodulator adenosine and , if applied in commonly consumed doses , evokes its stimulating effects through the blockade of adenosine receptors . 18F-8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ( 18F-CPFPX ) has been established as a highly selective and affine PET lig and for the A1 adenosine receptor ( A1AR ) . The objective of the present study was to visualize and quantify the in vivo occupancy of the human cerebral A1AR by caffeine using 18F-CPFPX and PET . Methods : Fifteen subjects ( age range , 24–68 y ) underwent a 140-min bolus – plus – constant-infusion PET experiment after at least 36 h of caffeine abstinence . Metabolite-corrected blood data were used to calculate steady-state distribution volumes ( VT ) during the baseline condition of the scan between 70 and 90 min . Subsequently , subjects received a 10-min infusion of varying concentrations ( 0.5–4.3 mg/kg of body weight ) of caffeine at 90 min . Occupancy VT of the A1AR was thereafter estimated using data acquired between 120 and 140 min . Occupancy levels were calculated using the Lassen plot , from which the inhibitory concentrations of 50 % were derived . Plasma levels of caffeine were determined at regular intervals . One subject received an intravenous vehicle as a placebo . Results : Caffeine displaced 5%–44 % of 18F-CPFPX binding in a concentration-dependent manner . There was no change of radiolig and binding after the administration of placebo . Half-maximal displacement was achieved at a plasma caffeine concentration of 67 μM , which corresponds to 450 mg in a 70-kg subject or approximately 4.5 cups of coffee . Conclusion : Given a biologic half-life of about 5 h , caffeine might therefore occupy up to 50 % of the cerebral A1AR when caffeinated beverages are repeatedly consumed during a day . Furthermore , the present study provides evidence that 18F-CPFPX PET is suitable for study ing the cerebral actions of caffeine , the most popular neurostimulant worldwide This study investigated effects of low ( 1 mg·kg-1 ) , moderate ( 3 mg·kg-1 ) and high ( 5 mg·kg-1 ) doses of caffeine on anaerobic performance in boys . Twenty-six 8- to 10-year-old boys participated in a double-blind , crossover , counter-balanced study . Boys received in r and om order a placebo ( PL ) or anhydrous caffeine : 1 ( CAF-1 ) , 3 ( CAF-3 ) , or 5 ( CAF-5 ) mg caffeine·kg-1 body mass in cherry flavored Sprite . Sixty minutes following consumption boys performed a static h and grip test and then a 30-s Wingate test . Maximal grip strength ( 21.5 ± 4.9 & 21.6 ± 4.7 vs. 20.4 ± 4.0 kg ) was significantly higher in CAF-5 & CAF-3 vs PL , respectively . Absolute and relative peak power ( 287 ± 72 vs 281 ± 69 W & 8.0 ± 0.9 vs 7.8 ± 1.0 W·kg-1 ) were significantly higher in CAF-3 vs PL , respectively . Mean power ( 153 ± 48 vs 146 ± 43 W ) was significantly higher in CAF-5 vs PL , respectively . Peak Wingate HR was significantly higher ( 189 ± 8 vs 185 ± 9 beats·min-1 ) in CAF-5 vs PL , respectively . These findings suggest that in boys CAF-1 did not affect performance . During the Wingate test CAF-3 result ed in higher peak power while CAF-5 increased mean power . The significant increase in peak HR following the Wingate test is likely related to greater mean power generated during CAF-5 The purpose of this study was to investigate the effectiveness of a caffeine-containing energy drink in enhancing rugby players ' physical performance during a simulated match . A second purpose was to determine the urinary caffeine excretion derived from the energy drink intake . In a r and omized and counterbalanced order , 26 elite rugby players ( mean ± SD for age and body mass , 25 ± 2 y and 93 ± 15 kg ) played 2 simulated rugby games ( 2 × 30 min ) 60 min after ingesting ( i ) 3 mg of caffeine per kilogram of body mass in the form of an energy drink ( Fure , ProEnergetics ) or ( ii ) the same drink without caffeine ( placebo ) . During the matches , the individual running distance and the instantaneous speed were measured , and the number of running actions above 20 km·h(-1 ) ( i.e. , sprints ) were determined , using global positioning system devices . The number of impacts above 5 g during the matches was determined by accelerometry . The ingestion of the energy drink , compared with the placebo , increased the total distance covered during the match ( 4749 ± 589 vs 5139 ± 475 m , p < 0.05 ) , the running distance covered at more than 20 km·h(-1 ) ( 184 ± 38 vs 208 ± 38 m , p < 0.05 ) , and the number of sprints ( 10 ± 7 vs 12 ± 7 , p < 0.05 ) . The ingestion of the energy drink also result ed in a greater overall number of impacts ( 481 ± 352 vs 641 ± 366 , p < 0.05 ) and a higher postexercise urine caffeine concentration ( 0.1 ± 0.1 vs 2.4 ± 0.9 μg·mL(-1 ) , p < 0.05 ) . The use of an energy drink with a caffeine dose equivalent to 3 mg·kg(-1 ) considerably enhanced the movement patterns of rugby players during a simulated match Background : This study was conducted to compare the pharmacokinetics of caffeine delivered using caffeinated chewing gum to that delivered using a marketed caffeinated beverage ( instant coffee ) in 16 healthy adult volunteers . Material s and Methods : This was a controlled open-label , r and omized , two-period crossover study . Caffeinated chewing gum and a serving of instant coffee , each containing ∼50 mg caffeine , were administered with blood sample s collected before and up to 24 hours after administration starts . Plasma caffeine levels were analyzed using vali date d liquid chromatography coupled with t and em mass spectrometry methodology . Results : There were no statistical differences between the two caffeine products in tmax ( p = 0.3308 ) and ka ( p = 0.3894 ) . Although formulated at ∼50 mg caffeine each , mean dose released from chewing gum was ∼18 % less than beverage . Dose-normalized area under the concentration – time curve (AUC)0-t , AUC0-∞ , and Cmax was similar between products . Although the criteria were not set a priori and the study was not powered for concluding bioequivalence , the 90 % confidence intervals fell within the bioequivalence limit of 80 % to 125 % . Conclusions : Existing scientific literature on caffeine , based mostly on data from caffeinated beverages , can be leveraged to support the safety of caffeine delivered by chewing gum and current maximum safe caffeine dose advice should be applicable irrespective of delivery method Abstract We examined the influence of caffeine supplementation on cognitive performance and perceptual responses in female team-game players taking low-dose monophasic oral contraceptives of the same hormonal composition . Ten females ( 24 ± 4 years ; 59.7 ± 3.5 kg body mass ; 2–6 training sessions per week ) took part in a r and omised , double-blind , placebo-controlled crossover- design trial . A 90-min intermittent treadmill-running protocol was completed 60 min following ingestion of a capsule containing either 6 mg • kg−1 anhydrous caffeine or artificial sweetener ( placebo ) . Perceptual responses ( ratings of perceived exertion ( RPE ) , feeling scale ( FS ) , felt arousal scale ( FAS ) ) , mood ( profile of mood states ( POMS ) ) and cognitive performance ( Stroop test , choice reaction time ( CRT ) ) were completed before , during and after the exercise protocol , as well as after ~12 h post exercise . Caffeine ingestion significantly enhanced the ratings of pleasure ( P = 0.008 ) and arousal ( P = 0.002 ) during the exercise protocol , as well as increased vigour ( POMS ; P = 0.007 ) , while there was a tendency for reduced fatigue ( POMS ; P = 0.068 ) . Caffeine ingestion showed a tendency to decrease RPE ( P = 0.068 ) and improve reaction times in the Stroop ( P = 0.072 ) and CRT ( P = 0.087 ) tests . Caffeine supplementation showed a positive effect on perceptual parameters by increasing vigour and a tendency to decrease fatigue during intermittent running activity in female games players taking low-dose monophasic oral contraceptive steroids ( OCS ) Abstract The study examined the effect of caffeine supplementation on match activities and development of fatigue during a football match . In a r and omised , double-blind cross-over design , two experimental football games separated by 7 days were organised between the junior teams of two professional football clubs ( 17.6 ± 1.1 years ( ±s ) , 71.7 ± 6.9 kg , 13.9 % ± 5.0 % body fat ) . The players ingested either a capsule of 6 mg · kg−1 b.w . caffeine or placebo ( dextrose ) 65 min prior to the matches . Match activities were assessed using the ZXY match analysis system , and a Yo-Yo intermittent recovery test – level 2 ( Yo-Yo IR2 ) was conducted immediately post-game . Heart rate was monitored throughout the game , and blood sample s were obtained at baseline , half-time and after the game . There were no differences between caffeine and placebo regarding total distance covered ( 10,062 ± 916 vs 9854 ± 901 m ) , high-intensity running ( 557 ± 178 vs 642 ± 240 m ) , sprinting distance ( 109 ± 58 vs 112 ± 69 m ) or acceleration counts ( 123 ± 31 vs 126 ± 24 ) . In both trials , players displayed lower ( P < 0.05 ) values in total distance and acceleration counts in the last 15 min compared to all other 15-min periods of the matches . Post-game Yo-Yo IR2 performance was not different between game trials ( caffeine : 829 ± 322 m ; placebo 819 ± 289 m ) . In conclusion , oral caffeine administration does not appear to have an ergogenic effect in young football players during match play This study investigated the effect of a caffeinated energy drink on various aspects of performance in sprint swimmers . In a r and omised and counterbalanced order , fourteen male sprint swimmers performed two acute experimental trials after the ingestion of a caffeinated energy drink ( 3 mg/kg ) or after the ingestion of the same energy drink without caffeine ( 0 mg/kg ; placebo ) . After 60 min of ingestion of the beverages , the swimmers performed a countermovement jump , a maximal h and grip test , a 50 m simulated competition and a 45 s swim at maximal intensity in a swim ergometer . A blood sample was withdrawn 1 min after the completion of the ergometer test . In comparison with the placebo drink , the intake of the caffeinated energy drink increased the height in the countermovement jump ( 49.4 ( SD 5.3 ) v. 50.9 ( SD 5.2 ) cm , respectively ; P<0.05 ) and maximal force during the h and grip test with the right h and ( 481 ( SD 49 ) v. 498 ( SD 43 ) N ; P<0.05 ) . Furthermore , the caffeinated energy drink reduced the time needed to complete the 50 m simulated swimming competition ( 27.8 ( SD 3.4 ) v. 27.5 ( SD 3.2 ) s ; P<0.05 ) , and it increased peak power ( 273 ( SD 55 ) v. 303 ( SD 49 ) W ; P < 0.05 ) and blood lactate concentration ( 11.0 ( SD 2.0 ) v. 11.7 ( SD 2.1 ) mM ; P<0.05 ) during the ergometer test . The caffeinated energy drink did not modify the prevalence of insomnia ( 7 v. 7 % ) , muscle pain ( 36 v. 36 % ) or headache ( 0 v. 7 % ) during the hours following its ingestion ( P>0.05 ) . A caffeinated energy drink increased some aspects of swimming performance in competitive sprinters , whereas the side effects derived from the intake of this beverage were marginal at this dosage Background The aim of this study was to examine the influence of caffeine supplementation on knee flexor and knee extensor strength before , during and after intermittent running exercise in female team-sport players taking oral contraceptive steroids ( OCS ) . Method Ten healthy females ( 24 ± 4 years ; 59.7 ± 3.5 kg ; undertaking 2–6 training sessions per week ) taking low-dose monophasic oral contraceptives of the same hormonal composition took part in a r and omised , double-blind , placebo-controlled crossover- design trial . Sixty minutes following the ingestion of a capsule containing 6 mg∙kg−1 body mass anhydrous caffeine or artificial sweetener ( placebo ) , participants completed a 90-min intermittent treadmill-running protocol . Isometric strength performance and eccentric and concentric strength and power of the knee flexors and knee extensors ( using isokinetic dynamometer ) , as well as countermovement jump ( CMJ ) , was measured before , during and after the exercise protocol , as well as ~12 h post-exercise . Blood sample s were taken before , during and post-exercise to measure glucose , insulin and free fatty acids ( FFA ) . Results Caffeine supplementation significantly increased eccentric strength of the knee flexors ( P < 0.05 ) and eccentric power of both the knee flexors ( P < 0.05 ) and extensors ( P < 0.05 ) . However , there was no effect on isometric or concentric parameters , or CMJ performance . FFA was elevated with caffeine supplementation over time ( P < 0.05 ) while levels of glucose and insulin were not affected by caffeine intake . Conclusion Caffeine supplementation increased eccentric strength and power in female team-sport players taking OCS both during an intermittent running protocol and the following morning The mechanism of action underlying the ergogenic effect of caffeine is still unclear . Caffeine increases the force of muscular contraction during low-frequency stimulation by potentiating calcium release from the sarcoplasmic reticulum . Studies have also suggested an enhancement of lipid oxidation and glycogen sparing as potential mechanisms . Given that several studies have found an ergogenic effect of caffeine with no apparent metabolic effects , it is likely that a direct effect upon muscle is important . Twelve healthy male subjects were classified as habitual ( n = 6 ) or nonhabitual ( n = 6 ) caffeine consumers based on a 4-day diet record analysis , with a mean caffeine consumption of 771 and 14 mg/day for each group , respectively . Subjects were r and omly allocated to receive caffeine ( 6 mg/kg ) and placebo ( citrate ) in a double-blind , cross-over fashion approximately 100 min before a 2-min tetanic stimulation of the common peroneal nerve in a custom-made dynamometer ( 2 trials each of 20 and 40 Hz ) . Tetanic torque was measured every 30 s during and at 1 , 5 , and 15 min after the stimulation protocol . Maximal voluntary contraction strength and peak twitch torque were measured before and after the stimulation protocol . Caffeine potentiated the force of contraction during the final minute of the 20-Hz stimulation ( P<0.05 ) with no effect of habituation . There was no effect of caffeine on 40-Hz stimulation strength nor was there an effect on maximal voluntary contraction or peak twitch torque . These data support the hypothesis that some of the ergogenic effect of caffeine in endurance exercise performance occurs directly at the skeletal muscle level There is little information about the effects of caffeine intake on female team-sport performance . The aim of this study was to investigate the effectiveness of a caffeine-containing energy drink to improve physical performance in female soccer players during a simulated game . A double-blind , placebo controlled and r and omized experimental design was used in this investigation . In two different sessions , 18 women soccer players ingested 3 mg of caffeine/kg in the form of an energy drink or an identical drink with no caffeine content ( placebo ) . After 60 min , they performed a countermovement jump ( CMJ ) and a 7 × 30 m sprint test followed by a simulated soccer match ( 2 × 40 min ) . Individual running distance and speed were measured using GPS devices . In comparison to the placebo drink , the ingestion of the caffeinated energy drink increased the CMJ height ( 26.6 ± 4.0 vs 27.4 ± 3.8 cm ; P < 0.05 ) and the average peak running speed during the sprint test ( 24.2 ± 1.6 vs 24.5 ± 1.7 km/h ; P < 0.05 ) . During the simulated match , the energy drink increased the total running distance ( 6,631 ± 1,618 vs 7,087 ± 1,501 m ; P < 0.05 ) , the number of sprints bouts ( 16 ± 9 vs 21 ± 13 ; P < 0.05 ) and the running distance covered at > 18 km/h ( 161 ± 99 vs 216 ± 103 m ; P < 0.05 ) . The ingestion of the energy drink did not affect the prevalence of negative side effects after the game . An energy drink with a dose equivalent to 3 mg of caffeine/kg might be an effective ergogenic aid to improve physical performance in female soccer players This study examined the effects of caffeine supplementation ( 6 mg·kg-1 ) on performance of a reactive agility test ( RAT ) in 17 elite , male , youth ( M = 14 y ) soccer players . Using a double-blind , repeated- measures design , players completed 4 days of testing on the RAT after a st and ardized warm-up . On day 1 , anthropometric measurements were taken and players were accommo date d to the RAT . On day 2 , baseline performance was established . Caffeine or placebo conditions were r and omly assigned on day 3 and the condition was reversed on day 4 . Players completed 3 r and omized trials of the RAT on days 2 , 3 , and 4 with at least 1 trial to the players ' dominant and nondominant sides . There were no significant differences among conditions in reaction time ( RT ) to the dominant side , heart rates at any point of measurement , or ratings of perceived exertion ( RPE ) after completion of the warm-up . Caffeine produced faster RT to the nondominant side ( P = .041 ) and higher RPE at the conclusion of the RAT ( P = .013 ) . The effect on the total time ( TT ) to complete the agility test to the nondominant side approached significance ( P = .051 ) . Sprint time and TT to either side did not differ . Caffeine supplementation may provide ergogenic benefit to elite , male , youth soccer players Background Energy drinks have become the most used caffeine-containing beverages in the sport setting . The aim of this study was to determine the effects of two doses of a caffeine-containing energy drink on muscle performance during upper- and lower-body power-load tests . Methods In a r and omized order , twelve active participants ingested 1 and 3 mg of caffeine per kg of body weight using a commercially available energy drink ( Fure ® , ProEnergetics ) or the same drink without caffeine ( placebo ; 0 mg/kg ) . After sixty minutes , resting metabolic rate , heart rate and blood pressure were determined . Then , half-squat and bench-press power production with loads from 10 to 100 % of 1 repetition maximum was determined using a rotator encoder . Results In comparison to the placebo , the ingestion of the caffeinated drink increased mean arterial pressure ( 82 ± 7 < 88 ± 8 ≈ 90 ± 6 mmHg for 0 mg/kg , 1 mg/kg , 3 mg/kg of caffeine , respectively ; P < 0.05 ) and heart rate ( 57 ± 7 < 59 ± 8 < 62 ± 8 beats/min , respectively ; P < 0.05 ) at rest in a dose response manner , though it did not affect resting metabolic rate . While the ingestion of 1 mg/kg of caffeine did not affect maximal power during the power-load tests with respect to the placebo , 3 mg/kg increased maximal power in the half-squat ( 2554 ± 167 ≈ 2549 ± 161 < 2726 ± 167 W , respectively ; P < 0.05 ) and bench-press actions ( 349 ± 34 ≈ 358 ± 35 < 375 ± 33 W , respectively ; P < 0.05 ) . Conclusions A caffeine dose of at least 3 mg/kg in the form of an energy drink is necessary to significantly improve half-squat and bench-press maximal muscle power UNLABELLED There is little evidence regarding the benefits of caffeine ingestion on cognitive function and skillful actions during sporting performance , especially in sports that are multifaceted in their physiological , skill , and cognitive dem and s. PURPOSE To examine the influence of caffeine on performance during simulated soccer activity . METHODS Twelve male soccer players completed two 90-min soccer-specific intermittent running trials interspersed with tests of soccer skill ( LSPT ) . The trials were separated by 7 days and adhered to a r and omized crossover design . On each occasion participants ingested 6 mg/kg body mass ( BM ) of caffeine ( CAF ) or a placebo ( PLA ) in a double-blind fashion 60 min before exercise . Movement time , penalties accrued , and total time were recorded for the LSPT . Physiological and performance markers were measured throughout the protocol . Water ( 3 ml/kg BM ) was ingested every 15 min . RESULTS Participants accrued significantly less penalty time in the CAF trial ( 9.7 + /- 6.6 s vs. PLA 11.6 + /- 7.4 s ; p = .02 ) , leading to a significantly lower total time in this trial ( CAF 51.6 + /- 7.7 s vs. PLA 53.9 + /- 8.5 s ; p = .02 ) . This decrease in penalty time was probably attributable to an increased passing accuracy in the CAF trial ( p = .06 ) . Jump height was 2.7 % ( + /- 1.1 % ) higher in the CAF trial ( 57.1 + /- 5.1 cm vs. PLA 55.6 + /- 5.1 cm ; p = .01 ) . CONCLUSIONS Caffeine ingestion before simulated soccer activity improved players ' passing accuracy and jump performance without any detrimental effects on other performance parameters Energy drinks are frequently consumed by athletes prior to competition to improve performance . This study examined the effect of Red Bull ™ on repeated sprint performance in women athletes . Fifteen collegiate soccer players participated , with mean age , height , and body mass equal to 19.5 ± 1.1 year , 168.4 ± 5.8 cm , and 63.4 ± 6.1 kg , respectively . After performing a familiarization trial , subjects performed three sets of eight bouts of the modified t test after ingestion of 255 mL of placebo or Red Bull 1 h pre-exercise in a r and omized , placebo-controlled crossover design . Throughout testing , sprint time , heart rate ( HR ) , and rating of perceived exertion ( RPE ) were continuously obtained . Repeated measures analysis of variance was used to examine differences in variables between drink conditions . Across athletes , t test time ranged from 10.4 to 12.7 s. Mean sprint time was similar ( p > 0.05 ) between Red Bull ( 11.31 ± 0.61 s ) and placebo ( 11.35 ± 0.61 s ) . HR and RPE increased ( p < 0.05 ) during the bouts , but there was no effect ( p > 0.05 ) of Red Bull on either variable versus placebo . Findings indicate that 255 mL of Red Bull containing 1.3 mg/kg of caffeine and 1 g of taurine does not alter repeated sprint performance , RPE , or HR in women athletes versus placebo . One serving of this energy drink provides no ergogenic benefit for women athletes engaging in sprint-based exercise OBJECTIVES To assess the effects of sodium phosphate ( SP ) and caffeine supplementation on repeated-sprint performance . DESIGN R and omized , double-blind , Latin-square design . METHODS Eleven team-sport males participated in four trials : ( 1 ) SP ( 50mgkg(-1 ) of free fat-mass daily for six days ) and caffeine ( 6mgkg(-1 ) ingested 1h before exercise ) ; SP+C , ( 2 ) SP and placebo ( for caffeine ) , ( 3 ) caffeine and placebo ( for SP ) and ( 4 ) placebo ( for SP and caffeine ) . After loading , participants performed a simulated team-game circuit ( STGC ) consisting of 2 × 30min halves , with 6 × 20-m repeated-sprint sets performed at the start , half-time and end of the STGC . RESULTS There were no interaction effects between trials for first-sprint ( FS ) , best-sprint ( BS ) or total-sprint ( TS ) times ( p>0.05 ) . However , SP result ed in the fastest times for all sprints , as supported by moderate to large effect sizes ( ES ; d=0.51 - 0.83 ) and ' likely ' to ' very likely ' chances of benefit , compared with placebo . Compared with caffeine , SP result ed in ' possible ' to ' likely ' chances of benefit for FS , BS and TS for numerous sets and a ' possible ' chance of benefit compared with SP+C for BS ( set 2 ) . Compared with placebo , SP+C result ed in moderate ES ( d=0.50 - 0.62 ) and ' possible ' to ' likely ' benefit for numerous sprints , while caffeine result ed in a moderate ES ( d=0.63 ; FS : set 3 ) and ' likely ' chances of benefit for a number of sets . CONCLUSIONS While not significant , ES and qualitative analysis results suggest that SP supplementation may improve repeated-sprint performance when compared with placebo ABSTRACT This study examined effects of 4 weeks of caffeine supplementation on endurance performance . Eighteen low-habitual caffeine consumers ( < 75 mg · day−1 ) were r and omly assigned to ingest caffeine ( 1.5–3.0 mg · kg−1day−1 ; titrated ) or placebo for 28 days . Groups were matched for age , body mass , V̇O2peak and Wmax ( P > 0.05 ) . Before supplementation , all participants completed one V̇O2peak test , one practice trial and 2 experimental trials ( acute 3 mg · kg−1 caffeine [ precaf ] and placebo [ testpla ] ) . During the supplementation period a second V̇O2peak test was completed on day 21 before a final , acute 3 mg · kg−1 caffeine trial ( postcaf ) on day 29 . Trials consisted of 60 min cycle exercise at 60 % V̇O2peak followed by a 30 min performance task . All participants produced more external work during the precaf trial than testpla , with increases in the caffeine ( 383.3 ± 75 kJ vs. 344.9 ± 80.3 kJ ; Cohen ’s d effect size [ ES ] = 0.49 ; P = 0.001 ) and placebo ( 354.5 ± 55.2 kJ vs. 333.1 ± 56.4 kJ ; ES = 0.38 ; P = 0.004 ) supplementation group , respectively . This performance benefit was no longer apparent after 4 weeks of caffeine supplementation ( precaf : 383.3 ± 75.0 kJ vs. postcaf : 358.0 ± 89.8 kJ ; ES = 0.31 ; P = 0.025 ) , but was retained in the placebo group ( precaf : 354.5 ± 55.2 kJ vs. postcaf : 351.8 ± 49.4 kJ ; ES = 0.05 ; P > 0.05 ) . Circulating caffeine , hormonal concentrations and substrate oxidation did not differ between groups ( all P > 0.05 ) . Chronic ingestion of a low dose of caffeine develops tolerance in low-caffeine consumers . Therefore , individuals with low-habitual intakes should refrain from chronic caffeine supplementation to maximise performance benefits from acute caffeine ingestion Summary The physiological effects of caffeine on subjects habituated to caffeine is relatively unstudied compared to those of caffeine naive subjects during grade d exercise . Thus , the purpose of this investigation was to determine the effects of caffeine on maximal oxygen consumption ( VO2max ) and the anaerobic threshold in these two population s. Seventeen moderately trained males were classified according to caffeine usage : ( 1 ) caffeine consumption 25 mg·day−1 or less ( CN ) ( n=8 ) or ( 2 ) caffeine consumption above 300 mg·day−1 ( CH ) ( n=9 ) . The subjects were tested post-absorptive on the same cycle ergometer on three occasions with 7 days separating the tests . One hour before each test the subject ingested either a gelatin capsule ( C ) ; 3 mg·kg−1 body weight of caffeine ( C3 ) ; or 5 mg·kg−1 body weight of caffeine ( C5 ) . The subject then performed an incrementalVO2max test beginning at 50 W and the work rate was increased 30 W every 2 min until the subject could not maintain the power output . Serial venous blood sample s were drawn over 30 s at the end of each stage . The CN group significantly increased resting heart rate ( fc ) and expired ventilation volume ( VE ) after C3 and C5 and VO2 after C5 . No significant differences were found for exerciseVE , VO2 , respiratory excharge ratio , fc or time to exhaustion . There were no significant differences ( P < 0.05 ) in the lactate threshold or the ventilatory threshold between treatment in either group . The CH subjects showed a significant increase ( P<0.05 ) in resting plasma free fatty acid ( FFA ) concentration only during the C3 and C5 treatments . Plasma FFA levels were significantly increased ( P < 0.05 ) at all times during C3 and C5 treatment in the CN subjects when compared to the control values . These data indicate that caffeine has no effect onVO2max or the anaerobic threshold seen during incremental , grade d exercise . However , resting metabolism and ventilation , and both resting and exercise plasma FFA are increased in CN subjects PURPOSE To determine whether a dose-response relationship exists between caffeine and 2000-m rowing performance . METHODS In this r and omized , placebo-controlled , double-blind crossover study , 10 competitive male rowers ( mean + /- SD : age = 20.6 + /- 1.4 yr , body mass = 87.7 + /- 10.5 kg , height = 186.8 + /- 6.8 cm , (.)VO2peak = 5.1 + /- 0.6 L x min(-1 ) ) consumed 2 , 4 , or 6 mg x kg(-1 ) caffeine or a placebo 60 min before completing a 2000-m time trial on a rowing ergometer . The trials were preceded by a 24-h st and ardized diet ( including a light preexercise meal of 2 g x kg(-1 ) CHO ) , and subjects were tested preexercise for hydration , caffeine abstinence , and blood glucose concentrations . RESULTS Time trial performance was not significantly different across the three caffeine doses or placebo ( P = 0.249 ) . After the three caffeine trials , postexercise plasma glucose and lactate concentrations were higher compared with the placebo trial ( P < 0.05 ) . Plasma caffeine concentrations after 60 min of ingestion were lower than the values reported previously by others following the same dose , and there was considerable interindividual variation in plasma caffeine concentrations in response to the various caffeine doses . CONCLUSIONS The large interindividual response to the caffeine doses suggests that individual characteristics need to be considered when administering caffeine for performance enhancement . In addition , preexercise feeding may significantly affect plasma caffeine concentrations and the potential for caffeine to improve performance Abstract In this study , we investigated the effect of ingesting carbohydrate alone or with caffeine on performance of a rugby union-specific shuttle running protocol . On three occasions , at least one week apart in a counterbalanced trial order , eight male rugby union forwards ingested either placebo or carbohydrate ( 1.2 g · kg−1 body mass · h−1 ) before and during a rugby union-specific protocol , with pre-exercise caffeine ingestion ( 4 mg · kg−1 ) before one of the carbohydrate trials ( carbohydrate + caffeine ) . The intermittent exercise protocol included walking , jogging , and cruising at pre-determined intensities , simulated contact events , a sustained high-intensity test of speed and agility ( Performance Test ) , and a 15-m sprint . Ratings of perceived exertion ( RPE ) were recorded every 5 min and a motor skills test was performed after each 21-min block . Performance Test times were not significantly different between trials but the likelihood of 2 % improvements for carbohydrate + caffeine over placebo and carbohydrate were 98 % and 44 % , respectively . For carbohydrate + caffeine , 15-m sprints were faster than for placebo ( P=0.05 ) and the motor skills test was performed faster in the carbohydrate + caffeine trial than the carbohydrate and placebo trials ( P < 0.05 ) , while RPE was lower in the carbohydrate + caffeine trial than the carbohydrate and placebo trials ( P < 0.05 ) . The results indicate a likely benefit to rugby performance following co-ingestion of carbohydrate and caffeine 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 . Heat and hypoxia exacerbate central nervous system ( CNS ) fatigue . We therefore investigated whether essential amino acid ( EAA ) and caffeine ingestion attenuates CNS fatigue in a simulated team sport-specific running protocol in a hot , hypoxic environment . Subelite male team sport athletes ( n = 8) performed a repeat sprint running protocol on a nonmotorized treadmill in an extreme environment on 4 separate occasions . Participants ingested one of four supplements : a double placebo , 3 mg.kg-1 body mass of caffeine + placebo , 2 x 7 g EAA ( Musashi Create)+placebo , or caffeine + EAA before each exercise session using a r and omized , double-blind crossover design . Electromyography ( EMG ) activity and quadriceps evoked responses to magnetic stimulation were assessed from the dominant leg at preexercise , halftime , and postexercise . Central activation ratio ( CAR ) was used to quantify completeness of quadriceps activation . Oxygenation of the prefrontal cortex was measured via near-infrared spectroscopy . Mean sprint work was higher ( M = 174 J , 95 % CI [ 23 , 324 ] , p < .05 , d = 0.30 ; effect size , likely beneficial ) in the caffeine + EAA condition versus EAAs alone . The decline in EMG activity was less ( M = 13 % , 95 % CI [ 0 , 26 ] ; p < .01 , d = 0.58 , likely beneficial ) in caffeine + EAA versus EAA alone . Similarly , the pre- to postexercise decrement in CAR was significantly less ( M = -2.7 % , 95 % CI [ 0.4 , 5.4 ] ; p < .05 , d = 0.50 , likely beneficial ) when caffeine + EAA were ingested compared with placebo . Cerebral oxygenation was lower ( M = -5.6 % , 95 % CI [ 1.0 , 10.1 ] ; p < .01 , d = 0.60 , very likely beneficial ) in the caffeine + EAA condition compared with LNAA alone . Co-ingestion of caffeine and EAA appears to maintain muscle activation and central drive , with a small improvement in running performance Abstract Clarke , JS , Highton , J , Close , GL , and Twist , C. Carbohydrate and caffeine improves high-intensity running of elite rugby league interchange players during simulated match play . J Strength Cond Res 33(5 ) : 1320–1327 , 2019—The study examined the effects of carbohydrate and caffeine ingestion on simulated rugby league interchange performance . Eight male elite rugby league forwards completed 2 trials of a rugby league simulation protocol for interchange players 7 days apart in a r and omized crossover design , ingesting either carbohydrate ( CHO ; 40 g·h−1 ) or carbohydrate and caffeine ( CHO-C ) ( 40 g·h−1 + 3 mg·kg−1 ) drink . Movement characteristics , heart rate , ratings of perceived exertion ( RPE ) , and countermovement jump ( CMJ ) height were measured during the protocol . CHO-C result ed in likely to very likely higher mean running speeds ( effect size [ ES ] 0.43–0.75 ) , distance in high-intensity running ( ES 0.41–0.64 ) , and mean sprint speeds ( ES 0.39–1.04 ) compared with CHO . Heart rate was possibly to very likely higher ( ES 0.32–0.74 ) , and RPE was likely to very likely lower ( ES −0.53 to 0.86 ) with CHO-C. There was a likely trivial to possibly higher CMJ in CHO-C compared with CHO ( ES 0.07–0.25 ) . The coingestion of carbohydrate with caffeine has an ergogenic effect to reduce the sense of effort and increase high-intensity running capability that might be used to enhance interchange running performance in elite rugby league players To determine the acute effect of an energy drink ( ED ) on physical performance of professional female volleyball players . 19 females ( age= 22.3 ± 4.9 yr . ; height= 171.8 ± 9.4 cm ; weight= 65.2 ± 10.1 kg ) participated in a r and omized , crossover , double-blind study to measure grip strength , vertical jump and anaerobic power in 3 different sessions ( ED , placebo [ PL ] or no beverage [ CTL ] ) . For each session , participants arrived in a fasted state , consumed a st and ardized breakfast meal , and 1 hr later completed the 3 baseline performance tests without having ingested the beverage . After completing the pre measurements , the athletes drank 6 ml/kg of body weight of the ED or PL and in the CTL condition no beverage was consumed . Posttest measurements were taken 30 min after the ingestion of liquids . A 3 × 2 repeated- measures ANOVA revealed no significant within-session and measurement time interactions for each performance test . Regardless of the measurement time , right h and grip strength was significantly higher in the ED condition ( 34.6 ± 0.9 kg ) compared with PL ( 33.4 ± 1.1 kg ) and CTL ( 33.6 ± 1.0 kg ) ( p < 0.05 ) . Regardless of the beverage ingested , averaged right h and grip strength , taking into account all 3 testing conditions , increased from pre to posttesting ( Pre = 33.8 ± 0.9 kg vs. Post = 33.9 ± 1.0 kg ; p = 0.029 ) , as did the averaged fatigue index , obtained from the anaerobic power test ( Pre = 65.9± 2.2 % vs. Post = 68.7± 2.0 % ; p= 0.049 ) . The acute ingestion of an ED did not improve physical performance of professional Costa Rican female volleyball players Abstract The effects of sodium phosphate and caffeine supplementation were assessed on repeated-sprint ability . Using a r and omised , double-blind , Latin-square design , 12 female , team-sport players participated in four trials : ( 1 ) sodium phosphate and caffeine , ( 2 ) sodium phosphate and placebo ( for caffeine ) , ( 3 ) caffeine and placebo ( for sodium phosphate ) and ( 4 ) placebo ( for sodium phosphate and caffeine ) , with ~21 days separating each trial . After each trial , participants performed a simulated team-game circuit ( 4 × 15 min quarters ) with 6 × 20-m repeated-sprints performed once before ( Set 1 ) , at half-time ( Set 2 ) , and after end ( Set 3 ) . Total sprint times were faster after sodium phosphate and caffeine supplementation compared with placebo ( Set 1 : P = 0.003 ; Set 2 : d = −0.51 ; Set 3 : P < 0.001 ; overall : P = 0.020 ) , caffeine ( Set 3 : P = 0.004 ; overall : P = 0.033 ) and sodium phosphate ( Set 3 : d = −0.67 ) . Furthermore , total sprint times were faster after sodium phosphate supplementation compared with placebo ( Set 1 : d = −0.52 ; Set 3 : d = −0.58 ) . Best sprint results were faster after sodium phosphate and caffeine supplementation compared with placebo ( Set 3 : P = 0.007 , d = −0.90 ) and caffeine ( Set 3 : P = 0.024 , d = −0.73 ) . Best sprint times were also faster after sodium phosphate supplementation compared with placebo ( d = −0.54 to −0.61 for all sets ) . Sodium phosphate and combined sodium phosphate and caffeine loading improved repeated-sprint ability Abstract Ribeiro , BG , Morales , AP , Sampaio-Jorge , F , Barth , T , de Oliveira , MBC , Coelho , GMdO , and Leite , TC . Caffeine attenuates decreases in leg power without increased muscle damage . J Strength Cond Res 30(8 ) : 2354–2360 , 2016—Caffeine ingestion has been shown to be an effective ergogenic aid in several sports . Caffeine administration may increase exercise capacity , which could lead to a greater degree of muscle damage after exercise . This was a r and omized , double-blind , placebo-controlled crossover study . Six male h and ball athletes ingested placebo ( PLA ) or caffeine ( CAF ) ( 6 mg·kg−1 body mass ) capsules on 2 different occasions . Sixty minutes after ingestion of the capsules , serum CAF levels were evaluated . Thereafter , all participants performed a protocol of vertical jumps ( VJs ) . The protocol consisted of 4 sets of 30 seconds of continuous VJs with 60 seconds of recovery between sets . Blood lactate ( LAC ) and creatine kinase ( CK ) levels were determined before and after the protocol . We found significant differences in serum CAF levels between PLA ( 0.09 ± 0.18 µg·ml−1 ) vs. CAF ( 6.59 ± 4.44 µg·ml−1 ) ( p < 0.001 ) . Caffeine elicited a 5.23 % ( p ⩽ 0.05 ) improvement in the leg power compared with PLA . The CAF trial displayed higher LAC ( p ⩽ 0.05 ) compared with PLA ( 6.26 ± 2.01 vs. 4.39 ± 2.42 mmol·L−1 , respectively ) after protocol of VJs , whereas no difference in CK was observed between trials ( p > 0.05 ) . These results indicate that immediate ingestion of CAF ( 6 mg·kg−1 body weight ) can reduce the level of muscle fatigue and preserve leg power during the test , possibly result ing in increase in LAC . There was no increase in muscle damage , which indicates that immediate administration of ( 6 mg·kg−1 body weight ) CAF is safe . Thus , nutritional interventions with CAF could help athletes withst and a greater physiological overload during high-intensity training sessions . The results of this study would be applicable to sports and activities that require repetitive leg power Abstract The goal of this r and omized , double-blind , cross-over study was to assess the acute effects of caffeine ingestion on muscular strength and power , muscular endurance , rate of perceived exertion ( RPE ) , and pain perception ( PP ) in resistance-trained men . Seventeen volunteers ( mean ± SD : age = 26 ± 6 years , stature = 182 ± 9 cm , body mass = 84 ± 9 kg , resistance training experience = 7 ± 3 years ) consumed placebo or 6 mg kg−1 of anhydrous caffeine 1 h before testing . Muscular power was assessed with seated medicine ball throw and vertical jump exercises , muscular strength with one-repetition maximum ( 1RM ) barbell back squat and bench press exercises , and muscular endurance with repetitions of back squat and bench press exercises ( load corresponding to 60 % of 1RM ) to momentary muscular failure . RPE and PP were assessed immediately after the completion of the back squat and bench press exercises . Compared to placebo , caffeine intake enhanced 1RM back squat performance ( + 2.8 % ; effect size [ ES ] = 0.19 ; p = .016 ) , which was accompanied by a reduced RPE ( + 7 % ; ES = 0.53 ; p = .037 ) , and seated medicine ball throw performance ( + 4.3 % , ES = 0.32 ; p = .009 ) . Improvements in 1RM bench press were not noted although there were significant ( p = .029 ) decreases in PP related to this exercise when participants ingested caffeine . The results point to an acute benefit of caffeine intake in enhancing lower-body strength , likely due to a decrease in RPE ; upper- , but not lower-body power ; and no effects on muscular endurance , in resistance-trained men . Individuals competing in events in which strength and power are important performance-related factors may consider taking 6 mg kg−1 of caffeine pre-training/competition for performance enhancement There are no scientific data about the effects of caffeine intake on volleyball performance . The aim of this study was to investigate the effect of a caffeine-containing energy drink to enhance physical performance in male volleyball players . A double-blind , placebo-controlled , r and omized experimental design was used . In 2 different sessions separated by 1 wk , 15 college volleyball players ingested 3 mg of caffeine per kg of body mass in the form of an energy drink or the same drink without caffeine ( placebo ) . After 60 min , participants performed volleyball-specific tests : st and ing spike test , maximal squat jump ( SJ ) , maximal countermovement jump ( CMJ ) , 15-s rebound jump test ( 15RJ ) , and agility T-test . Later , a simulated volleyball match was played and recorded . In comparison with the placebo drink , the ingestion of the caffeinated energy drink increased ball velocity in the spike test ( 73 ± 9 vs 75 ± 10 km/h , P < .05 ) and the mean jump height in SJ ( 31.1 ± 4.3 vs 32.7 ± 4.2 cm , P < .05 ) , CMJ ( 35.9 ± 4.6 vs 37.7 ± 4.4 cm , P < .05 ) , and 15RJ ( 29.0 ± 4.0 vs 30.5 ± 4.6 cm , P < .05 ) . The time to complete the agility test was significantly reduced with the caffeinated energy drink ( 10.8 ± 0.7 vs 10.3 ± 0.4 s , P < .05 ) . In addition , players performed successful volleyball actions more frequently ( 24.6 % ± 14.3 % vs 34.3 % ± 16.5 % , P < .05 ) with the ingestion of the caffeinated energy drink than with the placebo drink during the simulated game . A caffeine-containing energy drink , with a dose equivalent to 3 mg of caffeine per kg body mass , might be an effective ergogenic aid to improve physical performance and accuracy in male volleyball players |
2,235 | 31,915,177 | Our results show that although failure is reported in the studies , the level of detail prohibits a detailed analysis of failure of prophylaxis and pre-emptive therapy . | OBJECTIVES Infections remain a threat for solid organ and stem cell transplant recipients .
Antimicrobial prophylaxis and pre-emptive therapy have improved survival of these patients ; however , the failure rates of prophylaxis are not negligible .
The aim of this systematic review is to explore the reasons behind failure of antimicrobial prophylaxis and pre-emptive therapy . | OBJECTIVES Low-dose valganciclovir prophylaxis is still under investigation in renal transplant procedures . Our aim was to assess the cost effectiveness of 450 mg versus 900 mg valganciclovir prophylaxis in kidney transplant recipients . MATERIAL S AND METHODS In this prospect i ve trial , 201 kidney transplant patients were r and omized ( 1:1 ) to receive 450 mg/d ( group 1 , n = 100 ) or 900 mg/d ( group 2 , n = 101 ) valganciclovir prophylaxis for the first 6 months after transplant . Patients were studied for incidence of cytomegalovirus disease , leucopenia episodes , rejection episodes , and graft outcomes along with associated costs over 1 year . Costs ( in US dollars ) of treatment of rejection were also analyzed . RESULTS Demographic features of the studied groups were comparable . We found that the cost of cytomegalovirus care in group 1 patients was significantly lower ( by 50 % at 6 months ; P < .001 ) , with less leukopenia episodes ( P = .04 ) , lower doses of granulocyte colony-stimulating factor ( by 30 % at 6 months ; P = .03 ) , higher doses of mycophenolate mofetil ( P = .04 ) , and less rejection episodes ( P = .01 ) compared with group 2 . In group 2 , there were more episodes of cytomegalovirus infection ( P = .052 ) and BK virus nephropathy ( P = .04 ) . Graft and patient outcomes were satisfactory in both groups . CONCLUSIONS Low-dose valganciclovir for cytomegalovirus prophylaxis after renal transplant is safer , effective and without breakthrough infection , and less costly than using the usual dose Background Few studies have directly compared preemptive therapy ( PET ) and antiviral prophylaxis ( AP ) for prevention of cytomegalovirus ( CMV ) disease in CMV seropositive ( R+ ) orthotopic liver transplant ( OLT ) recipients . Methods We prospect ively assessed CMV disease and clinical outcomes among 160 consecutive R+ OLT recipients who received PET ( weekly plasma CMV PCR for 3 months , oral valganciclovir 900 mg twice daily for CMV viremia > 250 IU/mL , until 2 consecutive negative weekly PCR results ) and compared them with a historical cohort of 156 R+ recipients who received AP ( valganciclovir , 900 mg daily for 3 months ) . Results Patient characteristics were similar between PET and AP cohorts ( P > 0.05 all comparisons ) . In the PET group , 24 % ( 39/160 ) developed CMV viremia greater than 250 IU/mL at a median of 42 ( range , 7 - 93 ) days post-OLT . CMV monitoring adherence in the PET cohort was 85 % ( 1488/1760 required tests ) and 86 % ( 30/36 ) initiated PET within 3 days of the CMV result . By 12 months post-OLT , the incidence of CMV disease , acute allograft rejection , major infection , or death in the PET and AP cohorts was not significantly different : 2 % versus 2 % , 19 % versus 16 % , 10.5 % versus 10.8 % , and 5 % versus 8 % , respectively ( P > 0.05 all comparisons ) . The estimated proportion of drug-exposed patients and average antiviral drug exposure were significantly lower with PET versus AP : 24 % versus 100 % , P < 0.001 , and 15.8 versus 81 g per patient , P < 0.001 , respectively . Conclusions PET is feasible in a non research setting and is associated with similar CMV disease rates and other clinical ly relevant outcomes to AP in CMV seropositive liver transplant recipients OBJECTIVES Invasive fungal infections ( IFIs ) cause significant morbidity and mortality among recipients of hematopoietic stem cell transplantation ( HSCT ) . Although fluconazole is used widely as an antifungal prophylactic agent in these patients , it is not reliably effective against mold infection including invasive aspergillosis . Micafungin provides antifungal activity against C and ida and Aspergillus species , and previous studies have demonstrated its efficacy when used as a prophylactic agent for fungal infection in neutropenic patients . Here , we evaluated and compared the incidence of proven or probable IFIs after antifungal prophylaxis using micafungin or fluconazole . METHODS This was a prospect i ve , single-center , phase II study involving adult patients who received allogeneic or autologous HSCT . Patients were r and omly assigned to micafungin or fluconazole arms in a ratio of 2:1 , and the treatment was initiated within 24 h of HSCT and maintained for up to 21 days . The primary end point was the incidence of proven or probable IFIs during the 100 days after HSCT . The secondary end points were the incidence rates of possible , proven , or probable IFIs , need to change the antifungal agent before engraftment , IFI-related mortality , and survival within 100 days after transplantation . RESULTS Between March 2010 and May 2015 , a total of 257 patients were enrolled . After exclusion of seven patients who did not receive at least one dose of a study treatment , 250 patients ( micafungin , n = 165 ; fluconazole , n = 85 ) were included in the analysis of clinical efficacy . The median age was 47 years ( range , 20 - 64 ) . Allogeneic and autologous transplantations were performed in 56.0 % ( n = 140 ) and 44.0 % ( n = 110 ) of the patients , respectively . Baseline characteristics were well balanced between the two groups . Overall , the incidence of proven and probable IFIs within 100 days of HSCT was 7.6 % ( n = 19 ) . The percentages of patients who experienced proven or probable IFIs did not differ significantly between the micafungin and fluconazole groups : 7.3 % and 8.2 % , respectively ( p = 0.786 ) . Thirteen patients in the micafungin arm ( 7.9 % ) and eight patients in the fluconazole arm ( 9.4 % ) needed a change in antifungal agent before engraftment ( p = 0.824 ) . Mortality within 100 days after HSCT did not differ significantly between groups : 9.1 % vs 12.9 % in the micafungin and fluconazole arms , respectively ( p = 0.345 ) . CONCLUSION Micafungin is comparable to fluconazole for the prevention of IFIs in HSCT recipients Background The VIPP study compared valganciclovir prophylaxis with preemptive treatment regarding efficacy , safety , and long-term graft outcome in cytomegalovirus (CMV)-positive ( R+ ) renal transplant recipients . Methods Multicenter , open-label , r and omized clinical study with a 12-month study phase and a follow-up of up to 84 months . Patients in the prophylaxis group received 2 × 450 mg/d oral valganciclovir for 100 days adjusted to renal function . Preemptive treatment with 2 × 900 mg/d valganciclovir was initiated at a viral load of 400 CMV copies/mL or greater ( polymerase chain reaction ) and maintained over ≥14 days , followed by secondary prophylaxis . Patients were stratified by donor CMV IgG serostatus ( donor CMV IgG positive [D+]/R+ , donor CMV IgG negative [D−]/R+ ) . Results The 12-month results were reported previously ( Witzke et al Transplantation 2012 ) . The intent-to-treat/safety population comprised 148 patients in the prophylaxis ( 61.5 % D+/R+ ) and 151 patients in the preemptive group ( 52.3 % D+/R+ ) . Overall , 47 % patients completed the follow-up . Significantly fewer patients in the prophylaxis compared with preemptive group experienced a CMV infection or disease up to month 84 ( 11.5 % ; 95 % confidence interval [ 95 % CI ] , 6.8 - 17.8 % ] vs 39.7 % ; 95 % CI , 31.9 - 48.0 % ; P < 0.0001 and 4.7 % ; 95 % CI , 1.9 - 9.5 % vs 15.9 % ; 95 % CI , 10.5 - 22.7 % ; P = 0.002 ) . Incidences of graft loss ( 7.4 % vs 8.6 % ) , death ( 9.5 % vs 11.3 % ) , rejection ( 29.1 % vs 28.5 % ) , and renal function ( estimated glomerular filtration rate [ mean ± SD ] : 58.2 ± 26.3 vs 59.9 ± 25.7 mL/min per 1.73 m2 ) were not significantly different between prophylaxis and preemptive treatment . Tolerability was comparable between groups . Conclusions Prophylaxis was more effective than the preemptive approach , applying a low-intense surveillance protocol in preventing CMV infection and disease in intermediate-risk patients . Both strategies were similarly effective in preventing graft loss and death under the conditions of this long-term trial with a threshold of 400 copies/mL for initiation of anti-CMV treatment ABSTRACT Voriconazole prophylaxis is common following lung transplantation , but the value of therapeutic drug monitoring is unknown . A prospect i ve , observational study of lung transplant recipients ( n = 93 ) receiving voriconazole prophylaxis was performed . Serum voriconazole troughs ( n = 331 ) were measured by high-pressure liquid chromatography . The median initial and subsequent troughs were 1.91 and 1.46 μg/ml , respectively . The age of the patient directly correlated with initial troughs ( P = 0.005 ) . Patients that were ≥60 years old and cystic fibrosis patients were significantly more likely to have higher and lower initial troughs , respectively . In 95 % ( 88/93 ) of patients , ≥2 troughs were measured . In 28 % ( 25/88 ) and 32 % ( 28/88 ) of these patients , all troughs were ≤1.5 μg/ml or > 1.5 μg/ml , respectively . Ten percent ( 10/93 ) and 27 % ( 25/93 ) of the patients developed invasive fungal infection ( tracheobronchitis ) and fungal colonization , respectively . The median troughs at the times of positive and negative fungal cultures were 0.92 and 1.72 μg/ml ( P = 0.07 ) . Invasive fungal infections or colonization were more likely with troughs of ≤1.5 μg/ml ( P = 0.01 ) and among patients with no trough of > 1.5 μg/ml ( P = 0.007 ) . Other cutoff troughs correlated less strongly with microbiologic outcomes . Troughs correlated directly with aspartate transferase levels ( P = 0.003 ) , but not with other liver enzymes . Voriconazole was discontinued due to suspected toxicity in 27 % ( 25/93 ) of the patients . The troughs did not differ at the times of suspected drug-induced hepatotoxicity , central nervous system ( CNS ) toxicity , or nausea/vomiting and in the absence of toxicity . Voriconazole prophylaxis was most effective at troughs of > 1.5 μg/ml . A cutoff for toxicity was not identified , but troughs of > 4 μg/ml were rare . The data support a target range of > 1.5 to 4 μg/ml ABSTRACT Treatment of solid-organ transplant ( SOT ) patients with ganciclovir (GCV)-valganciclovir ( VGCV ) according to the manufacturer 's recommendations may result in over- or underexposure . Bayesian prediction based on a population pharmacokinetics model may optimize GCV-VGCV dosing , achieving the area under the curve ( AUC ) therapeutic target . We conducted a two-arm , r and omized , open-label , 40 % superiority trial in adult SOT patients receiving GCV-VGCV as prophylaxis or treatment of cytomegalovirus infection . Group A was treated according to the manufacturer 's recommendations . For group B , the dosing was adjusted based on target exposures using a Bayesian prediction model ( NONMEM ) . Fifty-three patients were recruited ( 27 in group A and 26 in group B ) . About 88.6 % of patients in group B and 22.2 % in group A reached target AUC , achieving the 40 % superiority margin ( P < 0.001 ; 95 % confidence interval [ CI ] difference , 47 to 86 % ) . The time to reach target AUC was significantly longer in group A than in group B ( 55.9 ± 8.2 versus 15.8 ± 2.3 days , P < 0.001 ) . A shorter time to viral clearance was observed in group B than in group A ( 12.5 versus 17.6 days ; P = 0.125 ) . The incidences of relapse ( group A , 66.67 % , and group B , 9.01 % ) and late-onset infection ( group A , 36.7 % , and group B , 7.7 % ) were higher in group A. Neutropenia and anemia were related to GCV overexposure . GCV-VCGV dose adjustment based on a population pharmacokinetics Bayesian prediction model optimizes GCV-VGCV exposure . ( This study has been registered at Clinical Trials.gov under registration no. NCT01446445 . It is unclear whether valganciclovir ( VGCV ) is effective compared with intravenous ganciclovir ( GCV ) for preemptive therapy of cytomegalovirus ( CMV ) infection in living donor liver transplantation ( LDLT ) . A r and omized trial was conducted to compare the efficacy of oral VGCV with intravenous GCV for preemptive treatment of CMV infection after LDLT . Patients who developed CMV infection within 6 months after LDLT at Tokyo University Hospital were r and omly assigned to the VGCV or GCV group and received either oral VGCV 900 mg/day or intravenous GCV 5 mg/kg twice daily , respectively . The primary endpoint was the treatment success rate . Secondary endpoints were recurrence of CMV infection within 1 year after finishing the treatment , and safety and tolerability of the treatment . Twenty-two patients with CMV infection after LDLT fulfilled the inclusion criteria and were r and omly assigned to the oral VGCV group ( n = 11 ) or the intravenous GCV group ( n = 11 ) . Treatment success rates were 82 % ( 9 of 11 ) and 91 % ( 10 of 11 ) in the VGCV and GCV groups , respectively . One patient in the VGCV group developed recurrence , whereas no patients in the GCV group developed recurrence . All the patients completed the treatment protocol , and no patients in either group dropped out of the study . In conclusion , oral VGCV and intravenous GCV are safe , feasible options for preemptive treatment of CMV infection after LDLT Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Reporting harms may cause more trouble and discredit than the fame and glory associated with successful reporting of benefits ( 1 ) . The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement , a checklist ( Table 1 ) flow diagram first published in 1996 and revised 5 years later ( 2 , 3 ) , is an effort to st and ardize , and thereby improve , published reports of r and omized , controlled trials ( RCTs ) . One of the additions to the 2001 revision was an item about reporting adverse events . This single item did not do full justice to the importance of harms-related issues . The CONSORT Group met in September 2001 to discuss how to correct this deficiency . We aim ed to provide evidence -based guidance on the reporting of harms in RCTs . First , we search ed MEDLINE , EMBASE , Web of Science , and the Cochrane Library using a wide array of terms related to harms and identified pertinent evidence . We also communicated with experts and review ed bibliographies of identified articles to find additional studies . At a meeting in Montebello , Quebec , Canada , in May 2003 , CONSORT Group members , including several journal editors and additional experts in related fields , held a structured discussion of recommendations about reporting of harms-related issues in RCTs . The discussion s led to a written document that we circulated among the team members for comment . The present manuscript describes our recommendations on the appropriate reporting of harms in RCTs . Table 1 . Original CONSORT Checklist The terminology of harms-related issues in RCTs is confusing and often misleading or misused ( see Glossary ) ( 4 , 5 ) . Safety is a reassuring term that may obscure the real and potentially major harms that drugs and other interventions may cause . We encourage authors to use the term harms instead of safety . In addition to misused terminology , reporting of harms in RCTs has received less attention than reporting of efficacy and effectiveness and is often inadequate ( 6 - 14 ) . In short , both scientific evidence and ethical necessity call for action to improve the quality of reporting of harms in RCTs ( 15 , 16 ) . Here , we present a set of recommendations and accompanying explanations for the proper reporting of harms in RCTs . These recommendations should complement the existing CONSORT statement ( Table 2 ) . Examples are presented on the Annals and CONSORT ( www.consort-statement.org ) Web sites . Table 2 . Checklist of Items To Include When Reporting Harms in R and omized , Controlled Trials Recommendations Title and Abstract Recommendation 1 . If the study collected data on harms and benefits , the title or abstract should so state . The title should mention harms if the study of harms was a key trial objective . Many phase I and phase II trials , some phase II/III trials , and most phase IV trials ( 17 , 18 ) target harms as primary outcomes . Yet , the title and abstract seldom contain the word harm . Among 375143 entries in the Cochrane Central Register of Controlled Trials ( Cochrane Library , issue 3 , 2003 ) , search ing titles with the search terms harm or harms yielded 337 references ( compared with 55374 for efficacy and 23415 for safety ) . Of the 337 , excluding several irrelevant articles on self-harm or harm reduction , only 3 trial reports and 2 abstract s contained the word harm in their titles . Authors should present information on harms in the abstract . If no important harms occurred , authors should so state . Explicit reference to the reporting of adverse events in the title or abstract is also important for appropriate data base indexing and information retrieval ( 19 ) . Introduction Background Recommendation 2 . If the trial addresses both harms and benefits , the introduction should so state . The introduction states the scientific background and rationale of an RCT . This requires a balanced presentation whereby the possible benefits of the intervention under investigation are outlined along with the possible harms associated with the treatment . R and omized , controlled trials that focus primarily on harms should clearly state this interest when describing the study objectives in the Introduction and in defining these objectives in the Methods . Methods Outcomes Recommendation 3 . List addressed adverse events with definitions for each ( with attention , when relevant , to grading , expected vs. unexpected events , reference to st and ardized and vali date d definitions , and description of new definitions ) . The Methods section should succinctly define the recorded adverse events ( clinical and laboratory ) . Authors should clarify whether the reported adverse events encompass all the recorded adverse events or a selected sample . They should explain how , why , and who selected adverse events for reporting . In trials that do not mention harms-related data , the Methods section should briefly explain the reason for the omission ( for example , the design did not include the collection of any information on harms ) . Authors should also be explicit about separately reporting anticipated and unexpected adverse events . Expectation may influence the incidence of reported or ascertained adverse events . Making participants aware in the consent form of the possibility of a specific adverse event ( priming ) may increase the reporting rate of the event ( 20 ) . Another example of priming is the finding that the rates of withdrawals due to adverse events and the rates of specific adverse events were significantly higher in trials of aspirin , diclofenac , or indomethacin with comparator drugs compared with placebo-controlled trials ( 21 ) . Presumably , participants were more eager to come forth and report an adverse event or to withdraw from treatment when they knew they could not be receiving inactive placebo . Authors should report whether they used st and ardized and vali date d measurement instruments for adverse events . Several medical fields have developed st and ardized scales ( 22 - 32 ) . Use of nonvali date d scales is common . The source document for well-established definitions and scales should be referenced . New definitions for adverse events should be explicit and clear . Authors should describe how they developed and vali date d new scales . For interventions that target healthy individuals ( for example , many preventive interventions ) , any harm , however minor , may be important to capture and report because the balance of harms and benefits may easily lean toward harms in a low-risk population . For other population s and for interventions that improve major outcomes ( for example , survival ) , severe and life-threatening adverse events may be the only ones that are important in the balance of benefits and harms . Recommendation 4 . Clarify how harms-related information was collected ( mode of data collection , timing , attribution methods , intensity of ascertainment , and harms-related monitoring and stopping rules , if pertinent ) . It is important to describe the question naires , interviews , and tests used to collect information on harms , as well as their timing during follow-up . Passive surveillance of harms leads to fewer recorded adverse events than active surveillance ( 4 ) . Open-ended questions may yield different information , both quantitatively and qualitatively , than structured question naires ( 33 ) . Studies of nonsteroidal , anti-inflammatory drugs ( NSAIDs ) exemplify how data collection methods can affect the detection and reporting of harms . When selective NSAIDs with fewer gastrointestinal adverse events became available , trials reported more than 10 times as many ulcers when comparing these drugs with older NSAIDs as when older NSAIDs were compared with placebo . In the newer trials , more ulcers were detected because participants had regular endoscopy , and the case definition of ulcers was more sensitive ( 34 ) . Authors should specify the time frame of surveillance for adverse events . Some investigators stop recording adverse events at the end of the intervention period or a certain number of days afterward ( for example , 30 days after discontinuation of drug therapy ) and miss events with long latency ( 35 ) . Surgical trials often capture only the adverse events that occur intraoperatively . Several important surgical complications are likely to occur later . Finally , in crossover trials , delayed events might occur while the patient is taking a subsequent assigned treatment . Attribution is the process of deciding whether an adverse event is related to the intervention . Whenever authors filter events through an attribution process , they should state who makes the attribution ( investigators , participants , sponsors , or combinations ) , whether the process is blinded to assigned treatment , and what definitions of adverse events they use ( 4 ) . Discontinuations and withdrawals due to adverse events are especially important because they reflect the ultimate decision of the participant and /or physician to discontinue treatment . Although treatment may occasionally be discontinued for mild or moderate adverse events , attributing discontinuation to a specific reason ( to toxicity , lack of efficacy , other reasons , or combinations of reasons ) may be difficult . For example , in psychopharmacology , dropouts may reflect treatment ineffectiveness as much as toxicity-related intolerance ( 36 ) . Trial reports should specify who gave the reasons for discontinuation ( participants or physicians ) and whether attribution was blinded to the assigned treatment . For example , even in blinded trials , participants and their clinicians are often unblinded before they decide whether to discontinue the intervention . It is important to report participants who are nonadherent or lost to follow-up because their actions may reflect their inability to tolerate the intervention . Moreover , authors should specify how they h and led withdrawals in the analyses of the data . R and omized , controlled trials should report any plan for monitoring for harms and rules for stopping the trial because of harms ( 37 ) . They should clarify whether stopping guidelines examine benefits and harms Late‐onset cytomegalovirus ( CMV ) disease is a significant problem with a st and ard 3‐month prophylaxis regimen . This multicentre , double‐blind , r and omized controlled trial compared the efficacy and safety of 200 days ’ versus 100 days ’ valganciclovir prophylaxis ( 900 mg once daily ) in 326 high‐risk ( D+/R– ) kidney allograft recipients . Significantly fewer patients in the 200‐day group versus the 100‐day group developed confirmed CMV disease up to month 12 posttransplant ( 16.1 % vs. 36.8 % ; p < 0.0001 ) . Confirmed CMV viremia was also significantly lower in the 200‐day group ( 37.4 % vs. 50.9 % ; p = 0.015 at month 12 ) . There was no significant difference in the rate of biopsy‐proven acute rejection between the groups ( 11 % vs. 17 % , respectively , p = 0.114 ) . Adverse events occurred at similar rates between the groups and the majority were rated mild‐to‐moderate in intensity and not related to study medication . In conclusion , this study demonstrates that extending valganciclovir prophylaxis ( 900 mg once daily ) to 200 days significantly reduces the incidence of CMV disease and viremia through to 12 months compared with 100 days ’ prophylaxis , without significant additional safety concerns associated with longer treatment . The number needed to treat to avoid one additional patient with CMV disease up to 12 months posttransplant is approximately 5 OBJECTIVES We performed a prospect i ve observational study comparing the efficacy and safety of low-dose ganciclovir ( 5 mg/kg/day ) as initial preemptive therapy in allogeneic haematopoietic stem cell transplantation ( HSCT ) recipients with conventional-dose ganciclovir ( 10 mg/kg/day ) . METHODS All adult patients undergoing allogeneic HSCT were enrolled at a transplant centre over a 24 month period . The decision to use low-dose or conventional-dose ganciclovir was at the discretion of each attending haematologist . A logistic regression model with inverse probability of treatment weighting ( IPTW ) using propensity scores was performed to reduce the effect of the selection bias in assignment for ganciclovir preemptive therapy . RESULTS Of the 252 HSCT recipients , 97 ( 38 % ) received preemptive ganciclovir therapy . Of these , 53 ( 55 % ) and 44 ( 45 % ) received low-dose and conventional-dose ganciclovir , respectively . The viral clearance rate was higher in the low-dose ganciclovir group [ 98 % ( 52/53 ) ] than in the conventional-dose ganciclovir group [ 86 % ( 38/44 ) , P = 0.04 ] , while the low-dose ganciclovir group exhibited a longer viral clearance time ( median 21.0 days ) than the conventional-dose ganciclovir group ( median 14.0 days , P = 0.05 ) . The rate of discontinuation of therapy due to neutropenia or nephrotoxicity was similar in the two groups , although conventional-dose ganciclovir was changed to another regimen more frequently than low-dose ganciclovir . There were three cases of cytomegalovirus ( CMV ) disease in each group after the initial preemptive therapy . The logistic regression models using propensity scores also revealed that there were no significant differences in viral clearance , secondary episodes of CMV infection , CMV disease and overall mortality between the two groups . CONCLUSIONS Low-dose ganciclovir appears to be safe , and to be at least as effective as conventional-dose ganciclovir for CMV viraemia in allogeneic HSCT recipients Background . Cytomegalovirus ( CMV ) prevention can be achieved by prophylaxis or preemptive therapy . We performed a prospect i ve r and omized trial to determine whether renal transplant recipients with a positive CMV serostatus ( R+ ) had a higher rate of CMV infection and disease after transplantation when treated preemptively for CMV infection , compared with primary valganciclovir prophylaxis . Methods . Prophylaxis was 2 × 450 mg oral valganciclovir/day for 100 days ; preemptive patients were monitored by CMV-polymerase chain reaction ( PCR ) , and after a positive PCR test received 2 × 900 mg valganciclovir/day for at least 14 days followed by secondary prophylaxis . Valganciclovir dosage was adjusted according to renal function . Patients are followed up for 5 years and initial 12-month data are presented . Two hundred and ninety-six recipients were analyzed ( 168 donor/recipient seropositive [ D+/R+ ] , 128 donor seronegative/recipient seropositive [ D−/R+ ] ; 146 receiving prophylaxis and 150 preemptive therapy ) . Results . Overall , CMV infection ( asymptomatic CMV viral load ≥400 CMV DNA copies/mL proven by CMV-PCR ) was significantly higher in recipients under preemptive therapy ( 38.7 % vs. 11.0 % , P<0.0001 ) , with the highest incidence in D+/R+ preemptive patients ( 53.8 % vs. 15.6 % , P<0.0001 ) . D+/R+ recipients with preemptive therapy also had the highest rate of CMV disease ( CMV syndrome and tissue-invasive disease that was clinical ly diagnosed and biopsy proven ) ( 19.2 % vs. 4.4 % , P=0.003 ) . Renal function assessed by creatinine clearance was similar for both groups . Graft loss occurred in 7 vs. 4 patients on preemptive versus prophylactic therapy ( P>0.05 ) . Tolerability was similar for both treatment groups . Conclusions . Oral valganciclovir prophylaxis significantly reduces CMV infection and disease , particularly for D+/R+ patients . Hence , our study supports routine prophylaxis for all D+/R+ recipients BACKGROUND A prospect i ve study was performed in kidney transplant patients at risk of developing cytomegalovirus ( CMV ) infection ( CMV D+/R- ) . They were treated with valganciclovir ( VGC ) for 3 months as prophylactic therapy . The aim was to determine the safety and efficacy of prophylactic therapy with VGC . METHODS Antigenemia and /or polymerase chain reaction CMV was routinely performed every 2 weeks up to month 3 , monthly to month 6 , and every other month until the end of the first year posttranplantation , as well as when clinical ly indicated . RESULTS From July 2007 to April 2010 , 366 renal transplantations were performed at our center , including 34 ( 9 % ) high-risk patients for CMV infection . The median age was 47 years ; 19 were males and 15 females . Twelve ( 35 % ) patients developed CMV infections : 10 ( 34 % ) gastrointestinal disease and 3 viral syndromes . The timing of the clinical manifestations was 16 % ( 3/12 ) between months 1 and 3 , 75 % ( 8/12 ) between months 4 and 6 , and 8 % ( 1/12 ) in month 9 posttransplantation . CONCLUSION Treatment with intravenous ganciclovir followed by oral VGC was successful in all patients . No opportunistic infections or allograft rejection were observed ; only 1 patient developed thrombocytopenia as an adverse event to VGC 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 High mortality rates of invasive fungal disease ( IFD ) , especially invasive aspergillosis ( IA ) , in immunocompromised haematological patients and current diagnostic limitations require improvement of detection of fungal pathogens by defining the optimal use of biomarkers and clinical sample s. Concurrent bronchoalveolar lavage ( BAL ) and peripheral blood sample s of 99 haematological patients with suspected IFD were investigated within a multicentre prospect i ve study . Diagnostic performance of a galactomannan ( GM ) enzyme immune assay ( EIA ) , a 1,3-β-D-glucan assay ( BDG ) , an Aspergillus PCR , and a multifungal DNA-microarray ( Chip ) alone or in combination were calculated . IFD were classified as proven ( n=3 ) , probable ( n=34 ) , possible ( n=33 ) , and no IFD ( n=29 ) according to EORTC/MSG criteria . GM , PCR , and Chip showed superior diagnostic performance in BAL than in blood , whereas specificity of BDG in BAL was poor ( 48 % ( 14/29 ) ) . The combination of GM ( BAL ) with BDG ( blood ) showed sensitivity , specificity , positive predictive value ( PPV ) , negative predictive value ( NPV ) , and DOR ( diagnostic odds ratio ) of 92 % ( 34/37 ) , 93 % ( 27/29 ) , 94 % , 90 % , and 153.0 , respectively . Combining GM ( BAL ) with PCR ( BAL ) showed convincing diagnostic potential for diagnosing IA with sensitivity , specificity , PPV , NPV , and DOR of 85 % ( 17/20 ) , 97 % ( 28/29 ) , 94 % , 90 % , and 158.7 . Addition of the DNA-microarray result ed in further detection of two mucormycetes infections . In 1 out of 15 Aspergillus DNA-positive sample s a triazole resistance-mediating Cyp51A mutation was found . Combination of biomarkers is superior to their sole use in diagnosing IFD , particularly IA . Integrating blood and BAL sample s into a diagnostic algorithm is an advantageous approach Editors ' Notes Context Cytomegalovirus ( CMV ) disease is a late complication of allogeneic hematopoietic cell transplantation ( HCT ) . Contribution In a multicenter , r and omized , double-blind trial of patients who had HCT and were at high risk for late CMV disease , continuous valganciclovir prophylaxis was compared with a strategy of CMV polymerase chain reactionguided preemptive therapy with valganciclovir and ganciclovir . These 2 approaches did not differ in the occurrence of death , CMV disease , or other invasive fungal infections . Safety was similar . Caution More patients who received continuous valganciclovir required hematopoietic growth factors . Implication Both continuous valganciclovir prophylaxis and CMV polymerase chain reactionguided preemptive therapy are viable alternatives to prevent late CMV disease after HCT . Ganciclovir effectively prevents cytomegalovirus ( CMV ) disease during the first 3 months after hematopoietic cell transplantation ( HCT ) when given prophylactically at engraftment or preemptively for pp65 antigenemia or detection of CMV DNA by polymerase chain reaction ( PCR ) . It improves survival in selected high-risk patients ( 1 , 2 ) . However , most cases of CMV disease now occur after withdrawal of ganciclovir ( 37 ) , most frequently between 100 and 270 days after transplantation ( 3 ) . In the absence of preventive strategies , both late CMV infection and disease are independent predictors for death after HCT ( 3 ) . Although preemptive therapy based on virologic surveillance is the most commonly used strategy to prevent CMV disease during the first 3 months after HCT ( 8) , maintaining surveillance is often difficult late after HCT because patients often return to remote locations and regular blood draws may be difficult to perform . The rationale for study ing a prophylactic approach is supported by the observation that even asymptomatic CMV infection is associated with increased mortality rates , suggesting a role of indirect effects of CMV in the late period ( 3 ) . However , the benefits of ganciclovir and valganciclovir prophylaxis are theoretically counterbalanced by their most common toxicity ( neutropenia ) , which is also independently associated with death early after HCT ( 9 , 10 ) . Methods Design This was an investigator-initiated , multicenter , double-blind , placebo-controlled , r and omized clinical trial . The Fred Hutchinson Cancer Research Center ( FHCRC ) held the Investigational New Drug application and served as the coordinating center . Patients were r and omly assigned to receive valganciclovir ( 900 mg once per day ) or matching placebo ( Appendix Figure 1 ) between 1999 and 2008 . Study patients , study personnel , and all clinical personnel were blinded . The study drug was withdrawn when CMV viral load was greater than 1000 copies/mL or greater than 5 times the baseline value , and preemptive therapy was started with intravenous ganciclovir ( 5 mg/kg twice daily ) or valganciclovir ( 900 mg twice daily ) ; foscarnet ( 90 mg/kg twice daily ) was used instead if indicated due to neutropenia . All doses were adjusted to the creatinine clearance as per manufacturer recommendations . Weekly study sample s were mailed to Seattle , Washington , and tested at the University of Washington clinical laboratories . Cytomegalovirus and chemistry testing results were made available in real time to study sites to allow initiation of open-label preemptive treatment of CMV disease , dose adjustment , drug withdrawal , or start of hematopoietic growth factors as prespecified in the protocol . The study drug was held and growth factors were started if the absolute neutrophil count decreased to less than 1.0109 cells/L. Appendix Figure 1 . Study design . CMV = cytomegalovirus ; HCT = hematopoietic cell transplantation . A CMV DNA level greater than 1000 copies/mL or consecutive positive results with increasing levels was used to withdraw the study drug and start preemptive treatment with open-label intravenous ganciclovir treatment . The protocol was amended halfway through the study to make valganciclovir open-label treatment available to patients for breakthrough preemptive therapy ( instead of requiring intravenous treatment ) and to formally include granulocyte colony-stimulating factor ( G-CSF ) treatment of neutropenia at an absolute neutrophil count of 1.0109 cells/L. Setting and Patients Allogeneic HCT recipients aged 16 years or older who were seropositive for CMV before transplant or had a seropositive donor were eligible . Seropositive recipients had to have either CMV infection with appropriate treatment course before r and om assignment ; a history of graft-versus-host disease ( GVHD ) after transplantation requiring treatment with systemic corticosteroids at doses greater than 0.5 mg/kg at any time before enrollment ; chronic , clinical ly extensive GVHD requiring treatment with corticosteroids ; or receipt of ganciclovir , valganciclovir , foscarnet , or cidofovir prophylaxis between engraftment and r and om assignment . Seronegative recipients with seropositive donors had to have a CMV infection with appropriate treatment course before r and om assignment . A complete listing of inclusion and exclusion criteria is shown in Appendix 1 . R and omization and Interventions R and omization occurred once patients were identified as eligible for the study at a median of 97 and 98 days after HCT for the valganciclovir and placebo groups , respectively ( Table 1 ) . We used an adaptive r and omization scheme implemented using a statistical program written by an FHCRC statistician and run by staff of the FHCRC protocol office . R and omization was stratified by study site , previous neutropenia ( presence or absence of absolute neutrophil count < 1.0109 cells/L after initial engraftment ) , and presence or absence of refractory GVHD ( requiring secondary therapy ) at study enrollment ( 11 , 12 ) . Table 1 . Demographic Characteristics of the Study Cohort , by Group * Outcomes and Follow-up The primary end point was a composite outcome consisting of CMV disease , invasive bacterial or fungal infections , or death ( whichever occurred first ) , thereby assessing the net effect of the strategy , including consequences of neutropenia ( 9 ) . Because most cases of late CMV disease occur between 4 and 9 months after HCT ( 35 ) , the primary study period for the intervention was until 270 days after HCT . Follow-up was extended until 640 days after HCT for CMV disease , death , and CMV-specific immune reconstitution . Secondary end points were CMV disease ( defined as per international guidelines [ 13 ] ) , death , invasive bacterial or fungal infections ( defined as published [ 1 , 14 ] ) ( Appendix 2 ) , use of invasive tests ( such as endoscopy procedures , including bronchoscopies ) , number of days alive without hospitalization during the active study period , treatment-emergent ganciclovir resistance , quality of life ( QOL ) as determined by the European Organization for Research and Treatment of Cancer Quality of Life Question naire 30 ( EORTC QLQ-30 ) ( 15 ) , herpesvirus-specific T-cell function , and adverse events ( clinical and laboratory ) . Laboratory Methods Cytomegalovirus viral load was determined at the University of Washington using a vali date d laboratory-developed quantitative PCR method ; the assay 's conversion factor to IU/mL is 1.0 ( 16 ) . Cytomegalovirus-specific T-cell function was determined by a multicolor flow cytometry assay design ed to detect polyfunctional CD4 + and CD8 + T cells ( 17 , 18 ) . Ganciclovir resistance was examined by testing patients with persistent or increasing viral load ( > 1000 copies/mL ) while receiving open-label treatment for mutations in the UL97 gene , using a rapid PCR- and sequencing-based assay as previously described ( 19 ) . Safety laboratory testing ( serum creatinine , alanine aminotransferase , blood differential , and platelet count ) was done using established methods and limits for normal or abnormal at the University of Washington clinical laboratories . Statistical Analysis The frequency of the primary composite end point was 53 % in our previous cohort ( 3 ) . Our study was design ed to test the superiority of the prophylactic strategy . To demonstrate a 45 % reduction of the primary end point ( which was deemed clinical ly meaningful ) , 184 r and omly assigned patients ( 92 per treatment group ) were needed to provide approximately 87 % power ( allowing for 1 interim analysis at the 0.005 level and a final analysis at the 0.048 level ) . All statistical tests were 2-sided . All patients who were r and omly assigned and received at least 1 dose of study medication were included in the analysis . Descriptive statistics were used to summarize demographic and baseline characteristics of study patients . Comparisons between study groups of time to the primary end point from HCT to 270 days after HCT were evaluated using Cox regression models adjusted for the stratification factors of neutropenia presence before r and om assignment or absence of an absolute neutrophil count less than 1.0109 cells/L after initial engraftment and study site ( FHCRC vs. other site ) . The number of patients with previous refractory GVHD was not sufficient to include this stratification factor . Secondary time-to-event outcomes were evaluated similarly ; some outcomes were evaluated to 640 days , as noted in Table 2 . Cumulative incidence curves were also used to evaluate time-to-event outcomes , with death as a competing risk for all outcomes except mortality ( 20 ) . All time-to-event analyses were censored at the time of last contact in the absence of a competing risk or event of interest . Absolute differences and associated 95 % CIs were evaluated using st and ard methods for risk differences for proportions ( 21 ) , but SEs of cumulative incidence were used to construct CIs for cumulative incidence . Differences in medians with CIs were evaluated using HodgesLehmann estimation ( 22 ) . Other secondary outcomes were compared between study groups with chi-square , Fisher exact , or Wilcoxon rank-sum tests , as appropriate . Subset analyses of efficacy and neutropenia Background Recurrence of prior invasive fungal infection ( relapse rate of 30–50 % ) limits the success of stem cell transplantation . Secondary prophylaxis could reduce disease burden and improve survival . Design and Methods A prospect i ve , open-label , multicenter trial was conducted evaluating voriconazole ( 4 mg/kg/12 h intravenously or 200 mg/12 h orally ) as secondary antifungal prophylaxis in allogeneic stem cell transplant recipients with previous proven or probable invasive fungal infection . Voriconazole was started 48 h or more after completion of conditioning chemotherapy and was planned to be continued for 100–150 days . Patients were followed for 12 months . The primary end-point of the study was the incidence of proven or probable invasive fungal infection . Results Forty-five patients were enrolled , 41 of whom had acute leukemia . Previous invasive fungal infections were proven or probable aspergillosis ( n=31 ) , proven c and idiasis ( n=5 ) and other proven or probable infections ( n=6 ) ; prior infection could not be confirmed in three patients . The median duration of voriconazole prophylaxis was 94 days . Eleven patients ( 24 % ) died within 12 months of transplantation , but only one due to systemic fungal disease . Three invasive fungal infections occurred post-transplant : two relapses ( one c and idemia and one fatal scedosporiosis ) and one new zygomycosis in a patient with previous aspergillosis . The 1-year cumulative incidence of invasive fungal disease was 6.7±3.6 % . Two patients were withdrawn from the study due to treatment-related adverse events ( i.e. liver toxicity ) . Conclusions Voriconazole appears to be safe and effective for secondary prophylaxis of systemic fungal infection after allogeneic stem cell transplantation . The observed incidence of 6.7 % ( with one attributable death ) is considerably lower than the relapse rate reported in historical controls , thus suggesting that voriconazole is a promising prophylactic agent in this population Human herpesvirus 6 ( HHV6 ) may be an important pathogen following allogeneic hematopoietic cell transplantation ( HCT ) . We prospect ively evaluated weekly HHV6 viremia testing after allogeneic HCT using a quantitative polymerase chain reaction (PCR)-based assay . HHV-6 viremia was detected in 46 of 82 ( 56 % ) patients at a median of 23 days post-HCT ( range : day + 10 to + 168 ) . More males ( 65 % vs females 39 % , P = .03 ) and recipients of umbilical cord blood ( UCB 69 % vs unrelated donor [ URD ] , 46 % vs sibling donor [ 20 % ] grafts , P = 0.01 ) reactivated HHV-6 . Patients with HHV6 viremia had more cytomegalovirus ( CMV ) reactivation ( 26 % vs 5.5 % , P = .01 ) and unexplained fever and rash ( 23.9 % vs 2.7 % , P = .01 ) compared with patients without HHV6 viremia . High-level HHV6 ( ≥ 25,000 copies/mL ) versus lower levels were associated with more culture-negative pneumonitis ( 72.7 % vs 22.8 % , P = .01 ) . Twenty HHV6-positive patients were treated with foscarnet , ganciclovir , or cidofovir for HHV6 or other coexistent viruses . Within 2 weeks , HHV6 viremia resolved more commonly in treated ( 65 % ) than untreated patients ( 31 % ) , P = .02 . Survival at 3 months was similar in treated and untreated patients ( 90 % vs 81 % , P = .4 ) . Survival at 3 and 6 months post-HCT were not affected by HHV6 positivity ( 3 months HHV6 + 85 % vs 78 % , P = .46 ; 6 months HHV6 + 70 % vs 72 % , P = .89 ) or by HHV6 level ( 3-month high level 73 % vs 89 % , P = .23 ; 6-month high level 64 % vs 71 % , P = .54 ) . Neither the occurrence of HHV6 , degree of viremia , nor use of antiviral drugs influenced short-term survival after HCT OBJECTIVES Prophylaxis for cytomegalovirus infection is highly recommended for kidney transplant recipients . The use of daily 900 mg valganciclovir is the usual prophylactic dose , whereas 450 mg daily is under investigation . We evaluated the outcome of using 2 different doses of valganciclovir prophylaxis for cytomegalovirus infection after kidney transplant . MATERIAL S AND METHODS We r and omized kidney transplant recipients ( 1:1 ) to receive 450 mg daily valganciclovir ( group 1 ) or 900 mg daily valganciclovir ( group 2 ) for the first 6 months after kidney transplant . Serologically , all patients were at moderate risk for cytomegalovirus infection . Patients were studied for incidence of cytomegalovirus disease , leukopenia attacks , rejection episodes , and graft outcomes for 1 year . RESULTS Demographic features of group 1 ( 98 patients ) and group 2 ( 98 patients ) were comparable . More than 50 % of patients received thymoglobulin induction therapy without difference between the groups . There were more leukopenia attacks in group 2 ( P = .03 ) requiring higher doses of granulocyte colony-stimulating factor ( P = .03 ) . Group 2 patients received lower doses of mycophenolate mofetil ( P= .04 ) and required reduced doses of valganciclovir ( P = .045 ) . Compared with group 1 , the high-dose group developed numerically more rejection episodes ( P = .057 ) and more cytomegalovirus infections requiring full treatment ( P = .17 ) . Graft and patient outcomes were satisfactory in both groups . CONCLUSION Six months of low-dose valganciclovir prophylaxis for intermediate-risk kidney transplant recipients was as effective as high-dose valganciclovir with a better safety profile BACKGROUND AND OBJECTIVES Both valganciclovir and high-dose valacyclovir are recommended for cytomegalovirus prophylaxis after renal transplantation . A head-to-head comparison of both regimens is lacking . The objective of the study was to compare valacyclovir prophylaxis with valganciclovir , which constituted the control group . DESIGN , SETTING S , PARTICIPANTS , & MEASUREMENTS In a r and omized , open-label , single-center trial , recipients of renal transplants ( recipient or donor cytomegalovirus-seropositive ) were r and omly allocated ( 1:1 ) to 3-month prophylaxis with valacyclovir ( 2 g four times daily ) or valganciclovir ( 900 mg daily ) . Enrollment occurred from November of 2007 to April of 2012 . The primary end points were cytomegalovirus DNAemia and biopsy-proven acute rejection at 12 months . Analysis was by intention to treat . RESULTS In total , 119 patients were assigned to valacyclovir ( n=59 ) or valganciclovir prophylaxis ( n=60 ) . Cytomegalovirus DNAemia developed in 24 ( 43 % ) of 59 patients in the valacyclovir group and 18 ( 31 % ) of 60 patients in the valganciclovir group ( adjusted hazard ratio , 1.35 ; 95 % confidence interval , 0.71 to 2.54 ; P=0.36 ) . The incidence of cytomegalovirus disease was 2 % with valacyclovir and 5 % with valganciclovir prophylaxis ( adjusted hazard ratio , 0.21 ; 95 % confidence interval , 0.01 to 5.90 ; P=0.36 ) . Significantly more patients with valacyclovir prophylaxis developed biopsy-proven acute rejection ( 18 of 59 [ 31 % ] versus 10 of 60 [ 17 % ] ; adjusted hazard ratio , 2.49 ; 95 % confidence interval , 1.09 to 5.65 ; P=0.03 ) . The incidence of polyomavirus viremia was higher in the valganciclovir group ( 18 % versus 36 % ; adjusted hazard ratio , 0.43 ; 95 % confidence interval , 0.19 to 0.96 ; P=0.04 ) . CONCLUSIONS Valganciclovir shows no superior efficacy in cytomegalovirus DNAemia prevention compared with valacyclovir prophylaxis . However , the risk of biopsy-proven acute rejection is higher with valacyclovir Background . Whether the early reduction in cytomegalovirus ( CMV ) disease seen at 1 year with prolongation of antiviral prophylaxis ( up to 200 days ) persists in the long term is unknown . Methods . This international , r and omized , prospect i ve , double-blind study , compared 318 CMV D+/R− kidney transplant recipients receiving valganciclovir ( 900 mg ) once daily for up to 200 days vs. 100 days . Long-term outcomes including CMV disease , acute rejection , graft loss , patient survival , and seroconversion were assessed . Results . At 2 years posttransplant , CMV disease occurred in significantly less patients in the 200- vs. the 100-day group : 21.3 % vs. 38.7 % , respectively ( P<0.001 ) . Between year 1 and 2 , there were only 10 new cases of CMV disease ; 7 in the 200-day group and 3 in the 100-day group . Patient survival was 100 % in the 200-day group and 97 % in the 100-day group ( p = not significant ) . Biopsy-proven acute rejection and graft loss rates were comparable in both groups ( 11.6 % vs. 17.2 % , P=0.16 , and 1.9 % vs. 4.3 % , P=0.22 , in the 200-day vs. 100-day groups , respectively ) . Seroconversion was delayed in the 200-day group but was similar to the 100-day group by 2 years posttransplant ( IgM or IgG seroconversion ; 55.5 % in the 200-day group vs. 62.0 % in the 100-day group at 2-years ; P=0.26 ) . Assessment of seroconversion at the end of prophylaxis was of limited utility for predicting late-onset CMV disease . Conclusion . Extending valganciclovir prophylaxis from 100 to 200 days is associated with a sustained reduction in CMV disease up to 2 years posttransplant BACKGROUND Antiviral prophylaxis against cytomegalovirus has been associated with reduced risk of allograft rejection and improved allograft survival after renal transplantation . This phenomenon might not be fully explained by preventing the indirect effects of cytomegalovirus . The effect of antiviral agents on lymphocyte function in patients treated with modern immunosuppression has not been studied to date . METHODS Adult renal transplant recipients were assigned to 3-month prophylaxis with either valganciclovir ( 900 mg once daily ; n=19 ) or valacyclovir ( 2 g four times daily ; n=17 ) as part of an ongoing r and omized trial . Subsets of lymphocytes , lymphocyte proliferation and /or cytokine production after in vitro mitogen stimulation were evaluated at the end of prophylaxis and 1 month after withdrawal of antiviral drugs . RESULTS Lymphocyte proliferation was significantly decreased both after phytohemagglutinine ( 25 % ±15 % versus 32 % ±18 % ; P=0.025 ) and concanavalin A stimulation ( 17 % ±9 % versus 25 % ±16 % ; P=0.011 ) during valganciclovir , but not valacyclovir therapy . Moreover , a lower activated T-cell count ( CD3(+)HLA-DR(+ ) cells ) was noted in valganciclovir-treated patients ( 13 % ±10 % versus 17 % ±12 % of total CD3(+ ) T-cells ; P=0.005 ) . CONCLUSIONS Valganciclovir suppresses lymphocyte proliferation and activation in patients after renal transplantation We studied the efficacy of two different doses of ganciclovir to prevent cytomegalovirus ( CMV ) disease in allogeneic hematopoietic stem cell transplantation ( HSCT ) recipients . We r and omly assigned allogeneic HSCT recipients who had CMV infection to receive preemptive ganciclovir therapy with or without induction phase ( 5 mg/kg twice daily for 1 week ) . Thirty-two and thirty-six patients were r and omized to the st and ard and the low-dose therapy group , respectively . The median time to CMV antigenemia or viremia clearance was 7 days ( 3–25 days ) in the st and ard therapy group versus 11 days ( 3–69 days ) in the low-dose therapy group ( P = 0.540 ) . The incidence of CMV disease was similar between the two groups ( P = 0.366 ) . The Kaplan – Meier estimate of event-free survival by day 180 after HSCT was 76.2 % in the st and ard therapy group versus 66.7 % in the low-dose therapy group ( P = 0.590 ) . Severe neutropenia ( < 0.5 × 109/L ) was observed in four ( 12.5 % ) patients in the st and ard therapy group versus two ( 5.6 % ) patients in the low-dose therapy group ( P = 0.314 ) . This study suggests that a low-dose ganciclovir preemptive therapy can be as effective as the st and ard-dose ganciclovir preemptive therapy for the prevention of CMV disease in allogeneic HSCT recipients Prevention of cytomegalovirus ( CMV ) is essential in organ transplantation . The two main strategies are pre-emptive therapy , in which one screens for and treats asymptomatic CMV viremia , and universal antiviral prophylaxis . We compared these strategies and examined long-term outcomes in a r and omized , open-label , single-center trial . We r and omly assigned 70 renal transplant recipients ( CMV-seropositive recipient or donor ) to 3-month prophylaxis with valacyclovir ( n=34 ) or pre-emptive valganciclovir for significant CMV viremia detected at predefined assessment s through month 12 ( n=36 ) . Among the 55 patients who had a protocol biopsy specimen available at 3 years to allow assessment of the primary outcome , 9 ( 38 % ) of 24 patients in the prophylaxis group and 6 ( 19 % ) of 31 patients in the pre-emptive therapy group had moderate to severe interstitial fibrosis and tubular atrophy ( odds ratio , 2.50 ; 95 % confidence interval , 0.74 - 8.43 ; P=0.22 ) . The prophylaxis group had significantly higher intrarenal mRNA expression of genes involved in fibrogenesis . The occurrence of CMV disease was similar in both groups , but pre-emptive therapy improved 4-year graft survival ( 92 % versus 74 % ; P=0.049 ) as a result of worse outcomes in patients with late-onset CMV viremia . In conclusion , compared with valacyclovir prophylaxis , pre-emptive valganciclovir therapy may lead to less severe interstitial fibrosis and tubular atrophy and to significantly better graft survival Background . Cytomegalovirus ( CMV ) is a significant cause of morbidity , mortality , and cost in solid organ transplant recipients . This study was conducted to measure both the clinical efficacy and the pharmacoeconomic impact of implementing , as st and ard of care , an abbreviated preemptive monitoring strategy compared with universal prophylaxis in a large teaching hospital . Methods . This prospect i ve observational study included only recipients at moderate risk for CMV infection , specifically recipients who were CMV seropositive before transplant . Recipients transplanted between February 2006 and December 2006 received prophylactic valganciclovir for 90 days after transplant , and those transplanted between January 2007 and December 2007 were enrolled in a preemptive monitoring strategy that included no anti-CMV prophylaxis but instead used serial CMV polymerase chain reactions in weeks 4 , 6 , 8 , 10 , 12 , 16 , 20 , and 24 to monitor the development of CMV DNAemia . Costs were analyzed from a societal perspective . Results . A total of 130 patients were included in this study . Baseline and transplant demographics are well matched between groups . CMV syndrome occurred in three patients in each group , and one patient in the preemptive group developed CMV disease . Thirty-seven percent of patients in the preemptive group developed CMV DNAemia , 68 % of these patients received antiviral therapy . Personnel and laboratory monitoring costs were significantly higher in the preemptive group , whereas medication cost was significantly higher in the prophylaxis group . Conclusions . Although outcomes and the overall cost of ( 1 ) universal prophylaxis and ( 2 ) preemptive monitoring are similar , universal prophylaxis places the cost burden on the patient whereas preemptive monitoring shifts the cost burden to the healthcare system Background Antifungal prophylaxis is shown to decrease the risk of invasive fungal infection ( IFI ) after hematopoietic stem-cell transplantation ( HSCT ) . Posaconazole has been approved for prophylaxis in HSCT . However , it is only available orally given three times per day . We evaluated once weekly intravenous amphotericin B lipid complex ( ABLC ) , given its broad-spectrum antifungal activity and prolonged half-life ( 172 hr ) , as an alternative prophylaxis in HSCT . Methods We prospect ively r and omized allogeneic HSCT patients to receive 7.5 mg/kg of intravenous ABLC weekly or 200 mg of posaconazole orally three times per day as prophylaxis for up to 6 weeks . Endpoints were the incidence of IFI and drug-related toxicities . ABLC was discontinued if creatinine level increased to two times the baseline or greater . Results A total of 46 patients were r and omized ; 40 received at least one dose of the drug and were included in the analysis : 19 received ABLC and 21 received posaconazole . All patients received tacrolimus . Apache II score , neutropenia , and creatinine , bilirubin , and alanine aminotransferase levels were similar in both groups at baseline . One patient in the ABLC arm and none in posaconazole arm developed IFI ( 5 % vs. 0 % , P=0.48 ) . More patients in the ABLC arm doubled their serum creatinine ( 53 % vs. 5 % , P=0.001 ) necessitating discontinuation of the study drug . Conclusion High-dose prophylactic ABLC in HSCT was associated with nephrotoxicity that could be aggravated by the concomitant use of other nephrotoxic agents . Further studies are needed to evaluate the role of weekly high-dose ABLC as antifungal prophylaxis in patients at lower risk for nephrotoxicity BACKGROUND The optimal approach to cytomegalovirus ( CMV ) prevention after lung transplantation is controversial . We recently completed a prospect i ve , r and omized , placebo-controlled study of CMV prevention in lung transplantation that demonstrated the short-term efficacy and safety of extending valganciclovir prophylaxis to 12 months vs 3 months of therapy . In the current analysis , we monitored a single-center subset of patients enrolled in the CMV prevention trial to determine if extended prophylaxis conferred a sustained long-term benefit and to assess its hematologic safety . METHODS The sub- analysis included 38 r and omized patients from Duke University Medical Center . All patients underwent consistent serial serum CMV monitoring and surveillance bronchoscopies . CMV was defined by viremia ( ≥ 500 CMV DNA copies/ml ) or pneumonitis . The safety assessment included a review of all complete blood counts obtained from transplant onward . RESULTS During a mean follow-up of 3.9 years in each group , extended-course compared with short-course prophylaxis provided a sustained protective benefit with a lifetime CMV incidence of 12 % vs 55 % , respectively ( hazard ratio , 0.13 ; 95 % confidence interval , 0.03 - 0.61 ; p = 0.009 ) , an effect that persisted after adjustment for clinical risk factors . Patients in each group underwent a comparable number of peripheral blood draws and bronchoscopies . Post-transplant white blood cell , neutrophil , and platelet counts were similar between each treatment group during the course of follow-up . CONCLUSION Extending valganciclovir prophylaxis to 12 months provides a durable long-term CMV protective benefit compared with short-course therapy , without increasing adverse hematologic effects We assessed the impact of antiviral prophylaxis and preemptive therapy on the incidence and outcomes of cytomegalovirus ( CMV ) disease in a nationwide prospect i ve cohort of solid organ transplant recipients . Risk factors associated with CMV disease and graft failure‐free survival were analyzed using Cox regression models . One thous and two hundred thirty‐nine patients transplanted from May 2008 until March 2011 were included ; 466 ( 38 % ) patients received CMV prophylaxis and 522 ( 42 % ) patients were managed preemptively . Overall incidence of CMV disease was 6.05 % and was linked to CMV serostatus ( D+/R− vs. R+ , hazard ratio [ HR ] 5.36 [ 95 % CI 3.14–9.14 ] , p < 0.001 ) . No difference in the incidence of CMV disease was observed in patients receiving antiviral prophylaxis as compared to the preemptive approach ( HR 1.16 [ 95 % CI 0.63–2.17 ] , p = 0.63 ) . CMV disease was not associated with a lower graft failure‐free survival ( HR 1.27 [ 95 % CI 0.64–2.53 ] , p = 0.50 ) . Nevertheless , patients followed by the preemptive approach had an inferior graft failure‐free survival after a median of 1.05 years of follow‐up ( HR 1.63 [ 95 % CI 1.01–2.64 ] , p = 0.044 ) . The incidence of CMV disease in this cohort was low and not influenced by the preventive strategy used . However , patients on CMV prophylaxis were more likely to be free from graft failure BACKGROUND Fungal infections are still one of the most important issue in liver transplant patients , contributing considerably to both morbidity and mortality . Few studies have been published comparing antifungal protocol s for their impact on liver transplant ( OLT ) patients . The aim of this study was to evaluate the effects of liposomal amphotericin B compared with fluconazole prophylaxis on morbidity and mortality after liver transplantation . METHODS We evaluated all 44 patients undergoing OLT from January 2006 to January 2009 who were enrolled and r and omized to undergo treatment with Amphotericin B ( 3 mg/kg/d ; group A = 25 patients ) or fluconazole ( 800 mg Loading dose and thereafter 400 mg/d according to renal parameters and immunosuppressant trough levels ; group B = 18 patients ) for at least 7 to 14 days with 12 months follow-up after liver transplantation . A multivariate analysis assessed factors associated with infections and mortality . RESULTS Neither antifungal prophylaxis was associated with a fungal episode ; however , group A patients experienced fewer bacterial infectious episodes ( Mann-Whitney U test P < .05 ) . Furthermore , no renal impairment was observed in either groups . Nonetheless , patients undergoing fluconazole prophylaxis showed significant increases in immunosuppressive trough levels requiring dose adjustment . CONCLUSION We observed comparable results of fluconazole and liposomal amphotericin B to prevent invasive fungal infections throughout 12 months after surgery . The latter drug was associated with fewer bacterial infections after liver transplantation BACKGROUND The main challenge with cytomegalovirus ( CMV ) prophylaxis in IgG donor-positive/recipient-negative ( D+/R- ) kidney transplant recipients is late-onset CMV disease . We evaluated a novel protocol for the prevention of late-onset CMV infection and disease in D+/R- organ recipients . METHODS Our prospect i ve , observational , cohort study included 100 adult kidney transplant recipients . Prophylaxis with low-dose valganciclovir ( 450 mg/d , 3 times a week for 6 months ) was administered to D+/R- recipients . Risk factors for CMV infection and disease were identified . Renal function and the outcomes of CMV infection and disease were compared between D+/R- ( n = 15 ) and recipient-positive ( R+ ; n = 81 ) organ recipients . RESULTS D+/R- recipients showed significant independent risk factors with high hazard ratios for CMV infection ( 2.04 ) and disease ( 10.3 ) . The proportion of CMV infection in D+/R- and R+ recipients was 80 % and 46 % ( P = .023 ) , and that of CMV disease was 33 % and 6.2 % ( P = .008 ) , repectively . D+/R- recipients developed CMV infection and disease within 6 months after transplantation . However , both CMV infection- and disease-free survival rates beyond 1 year post-transplantation defined as late-onset were stable in D+/R- recipients . Moreover , serum creatinine levels at 1 year post-transplantation were comparable between D+/R- and R+ recipients ( 1.45 ± 0.71 vs 1.16 ± 0.35 mg/dL , P = .26 ) . CONCLUSION Our novel protocol prevented late-onset CMV infection and disease beyond 1 year post-transplantation in D+/R- recipients Preemptive therapy for cytomegalovirus ( CMV ) infection in allogeneic hematopoietic stem cell transplant ( HSCT ) patients is effective in decreasing the incidence of CMV disease . Intravenous ganciclovir is a commonly used preemptive therapy , but as we have recently shown , oral valganciclovir ( VGC ) is a useful alternative . However , the optimal dose of VGC has not been determined . We prospect ively evaluated the efficacy and toxicity of an initial low-dose of VGC ( 900 mg QD ) as preemptive therapy in 20 patients with low-level CMV antigenemia following allogeneic HSCT . Patients were screened weekly for CMV pp65 antigenemia after engraftment . Preemptive therapy with VGC ( 900 mg QD ) was initiated if more than two CMV antigen-positive cells per 50,000 leukocytes were detected . CMV antigen-positive cells disappeared from all 20 patients after 14–29 days ( median 20 days ) of VGC treatment . None of the patients developed CMV disease nor did they require more than the conventional VGC dose ( 900 mg BID ) . Neutropenia ( < 500/μL ) developed in three patients who required granulocyte-colony-stimulating factor support , but there were no other significant side effects . These observations suggest that the initial dose of VGC in preemptive therapy for CMV can be safely decreased to 900 mg QD for patients with low-level CMV antigenemia BACKGROUND Cytomegalovirus ( CMV ) is the most prevalent opportunistic infection after lung transplantation . Current strategies do not prevent CMV in most at-risk patients . OBJECTIVE To determine whether extending prophylaxis with oral valganciclovir from the st and ard 3 months to 12 months after lung transplantation is efficacious . DESIGN R and omized , clinical trial . Patients were r and omly assigned by a central automated system to treatment or placebo . Patients and investigators were blinded to treatment status . ( Clinical Trials.gov registration number : NCT00227370 ) SETTING Multicenter trial involving 11 U.S. lung transplant centers . PATIENTS 136 lung transplant recipients who completed 3 months of valganciclovir prophylaxis . INTERVENTION 9 additional months of oral valganciclovir ( n = 70 ) or placebo ( n = 66 ) . MEASUREMENTS The primary end point was freedom from CMV disease ( syndrome or tissue-invasive ) on an intention-to-treat basis 300 days after r and omization . Secondary end points were CMV disease severity , CMV infection , acute rejection , opportunistic infections , ganciclovir resistance , and safety . RESULTS CMV disease occurred in 32 % of the short-course group versus 4 % of the extended-course group ( P < 0.001 ) . Significant reductions were observed with CMV infection ( 64 % vs. 10 % ; P < 0.001 ) and disease severity ( 110 000 vs. 3200 copies/mL , P = 0.009 ) with extended treatment . Rates of acute rejection , opportunistic infections , adverse events , CMV UL97 ganciclovir-resistance mutations , and laboratory abnormalities were similar between groups . During the 6 months after study completion , a low incidence of CMV disease was observed in both groups . LIMITATION Longer-term effects of extended prophylaxis were not assessed . CONCLUSION In adult lung transplant recipients who have received 3 months of valganciclovir , extending prophylaxis by an additional 9 months significantly reduces CMV infection , disease , and disease severity without increased ganciclovir resistance or toxicity . A beneficial effect with regard to prevention of CMV disease seems to extend at least through 18 months after transplantation |
2,236 | 26,348,686 | CONCLUSIONS Different outcome measures are used in therapeutic trials on functional disorders of the upper gastrointestinal tract . | OBJECTIVES Functional disorders of the upper gastrointestinal tract are frequently diagnosed in children .
Four different clinical entities are addressed by the Rome III committee : functional dyspepsia ( FD ) , cyclic vomiting syndrome ( CVS ) , adolescent rumination syndrome ( ARS ) , and aerophagia .
Management of these disorders is often difficult leading to a wide variety in therapeutic interventions .
We hypothesize that definitions and outcome measures in these studies are heterogeneous as well .
Our aim is to systematic ally assess how these disorders and outcomes are defined in therapeutic r and omized controlled trials ( RCTs ) . | Background and Aim : Chronic abdominal pain ( AP ) is common in children . Recall of symptoms is used clinical ly to determine management , to assess treatment progress , and in drug studies to assess outcomes . Limited data exist on accuracy of AP recall in children . The aim of the present study was to assess ability to accurately recall AP in children . Methods : The study was a secondary analysis of data obtained from a double-blind , r and omized , placebo-controlled trial , evaluating amitriptyline in children with functional gastrointestinal disorders . Children ages 8 to 17 years with AP predominant functional gastrointestinal disorders based on Rome II criteria were recruited from 6 centers . Those with evidence of organic disease were excluded . Patients maintained AP diary daily for 1 month ( presence , frequency , and intensity ) . At the end of the study , patients reported the number of days of AP during previous month . Agreement between daily pain reports and recalled pain was assessed . Univariate analysis was conducted with Spearman rank correlations . Results : We recruited 63 children ( 45 girls , mean age 12.8 years ) . Sixteen percent children had perfect agreement on number of days of AP . Fifty-four percent of children recalled fewer episodes of pain . The average number of days with AP by recall was 17.7/month , whereas by diary it was 23.5/month ( P = 0.001 ) . Correlation between patient recall of the last week of symptoms ( r = 0.47 ) was no better than correlation between recall of the last 30 days of symptoms ( r = 0.48 ) . On comparing AP recall versus various pain intensities , reported AP did not reflect only AP of greater severity . Higher correlation of recall of symptoms was seen in children 11 years or younger ( r = 0.59 ) as compared with children older than 11 years ( r = 0.26 ) . Conclusions : Few children can accurately recall the episodes of AP . Children commonly recall a lower frequency of AP than that assessed by prospect i ve diary reports . Reported recall does not reflect a shorter re collection period . Recall is not related to intensity of pain . Adolescents have worse recall of symptoms Objective : Aerophagia is a functional gastrointestinal disorder characterised by repetitive air swallowing , abdominal distension , belching , and flatulence . In severe cases , it can lead to pneumoperitonium , volvulus of the colon , and intestinal perforation . Little is known about the epidemiology and clinical profile of affected children . The main objective of the present study was to assess the epidemiology of aerophagia in 10- to 16-year-olds in Sri Lanka . Methods : A school-based cross-sectional survey was conducted in 8 r and omly selected schools in 4 r and omly selected provinces in Sri Lanka . Data were collected using a pretested , self-administered question naire , which was distributed in an examination setting and collected on the same day . Trained research assistants were present during completion of the question naire , for any required clarification . Aerophagia was diagnosed using the Rome III criteria . Results : In the present study , aerophagia was seen in 163 ( 7.5 % ) of the 2163 children evaluated . The prevalence was higher in older children ( 10.5 % in 15-year-olds ) and no sex difference was observed ( boys 8.2 % vs girls 6.8 % , P > 0.05 ) . Intestinal-related ( abdominal pain , nausea , and anorexia ) and extraintestinal symptoms ( headache , limb pain , sleeping difficulty , photophobia , and lightheadedness ) were more prevalent among affected children ( P < 0.05 ) . A higher percentage of affected children were found to be exposed to stressful events when compared with controls ( P < 0.05 ) . Conclusions : The present study highlights the high prevalence of aerophagia among Sri Lankan children and adolescents . This condition is more common in those exposed to emotional stress . Intestinal-related symptoms and extraintestinal somatic symptoms are frequently seen in affected children AIM To evaluate the clinical presentation , response to prophylactic therapy and outcome of children with cyclic vomiting syndrome ( CVS ) in Shiraz , Iran . METHODS During a period of 11 years ( March 1994 to March 2005 ) , 181 consecutive children with a final diagnosis of CVS were evaluated , treated and followed in our center . Patients were r and omized to receive either amitriptyline or propranolol as prophylactic treatments . RESULTS There were 88 boys and 93 girls with mean age of onset of symptoms of 4.9 + /- 3.3 years ( range , neonatal period to 14 years ) , the mean age at final diagnosis was 6.9 years ( range , 1.5 to 14 ) , and the mean duration between the onset of the first attack and the final diagnosis of CVS was 2 + /- 1.81 years ( range , 1/6 to 8) . The mean duration of each attack was 4.26 days ( range , from few hours to 10 d ) and the mean interval between the attacks was 1.8 mo ( range , 1 wk to 12 mo ) . The time of onset of the attacks was midnight to early morning in about 70 % of cases . Amitriptyline was effective in 46 out of 81 ( 56 % ) patients ( P < 0.001 ) . Propranolol appeared to have a superior action and was effective in 74 out of 83 ( 92 % ) patients ( P < 0.0001 ) . CONCLUSION There is a significant lag time between the onset of clinical symptoms and the final diagnosis of CVS in our area . In patients with typical clinical presentations of CVS , who are examined by an experienced physician , invasive workup is not necessary . Propranolol appears more effective than amitriptyline for prophylactic use in children with CVS BACKGROUND To date , no patient reported outcomes ( PRO ) instrument is available for evaluation of treatment efficacy in functional dyspepsia (FD)/postpr and ial distress syndrome ( PDS ) . The aim of our study was to perform focus group interviews for the development of a new question naire for assessing symptom pattern and severity in PDS . METHODS R and om ambulatory patients diagnosed with FD/PDS based on Rome III criteria and no predominant gastro-esophageal reflux disease ( GERD ) symptoms were invited to participate . Focus group sessions were organized where patients reported and discussed their symptoms , facilitated by an experienced physician . After reaching saturation of identified symptom items , questions for a pilot PRO instrument were drafted and evaluated in cognitive interviews for relevance , clarity , and consistency . KEY RESULTS Of 225 screened patients , 26 patients were diagnosed with PDS without overlapping GERD as single final diagnosis . Fifteen of these ( 87 % female , 48 ± 3.2 years ) participated in one of three focus groups . All ( 100 % ) confirmed experiencing symptoms that were triggered or aggravated by ingestion of a meal , corresponding to early satiation ( 100 % ) , and postpr and ial fullness ( 100 % ) . In addition reported gastroduodenal symptoms were nausea ( 40 % , postpr and ial in all , interpr and ial in 20 % ) , upper abdominal bloating ( 33 % ) , excessive belching ( 27 % ) , and vomiting ( 13 % ) . Epigastric pain and burning were present in respectively 20 % and 13 % . Non-gastroduodenal symptoms that patients reported included heartburn ( 33 % , but mostly sporadic ) , weight loss ( 93 % , on average 5.0 ± 1.7 kg ) , and fatigue ( 67 % ) . Questions evaluating these symptoms were vali date d in 15 cognitive interviews . CONCLUSIONS & INFERENCES This focus group study confirms symptoms corresponding to postpr and ial fullness and early satiation as the key items for developing a PRO for PDS Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists AIM To look at predictors of consulting behaviour among children with recurrent abdominal pain in a rural community in Malaysia . SUBJECTS AND METHODS A sample of 1462 school-children aged between 9 and 15 years were r and omly selected from all schools in Kuala Langat , a rural district in Malaysia . Those with recurrent abdominal pain , defined according to Apley 's criteria , were recruited and divided into consulters and non-consulters . A consulter was defined as a child who had sought the help of a medical practitioner at least once in the past year for recurrent abdominal pain . A detailed clinical , social and family history was obtained in all recruited children . RESULTS A total of 161 children were recruited : 78 ( 48.4 % ) consulters , 83 ( 51.6 % ) non-consulters . Of the consulters , 40 were boys , 38 were girls ( male : female ratio = 1.1:1 ) . The two sexes did not show a significant difference in prevalence of consulters [ p=0.189 ) . Of the ethnic groups , only Indians had a significantly higher likelihood to consult a doctor ( Indians , p=0.006 ; Malays , p=0.742 ; Chinese , p=0.050 ] . Younger children ( under 12 years ) had a significantly higher chance of having been brought to see a medical practitioner ( p=0.014 ) . Children in whom age of onset of abdominal pain was below ten years were also more likely to have been seen by a doctor ( p=0.012 ) . Children who had consulted a doctor were more likely to be missing school because of abdominal pain ( p<0.001 ) . Pain severity was not a significant factor ( p=0.429 ) . Multiple logistic regression analysis revealed that the only variable that remained significantly associated with health-care consultation was school absence ( p<0.001 ) . CONCLUSIONS Children who saw their doctors for recurrent abdominal pain were also more likely to be those who missed school on account of abdominal pain . Following multiple regression analysis , other factors were no longer significant OBJECTIVES : Functional GI disorders ( FGIDs ) are common in clinical practice , but little is known about the epidemiology of these disorders in the general population . We aim ed to determine the prevalence , association with psychological morbidity , and health care seeking behavior of FGIDs in the population . METHODS : A r and om sample of subjects ( n = 4500 ) aged ≥18 yr and representative of the Australian population were mailed a vali date d question naire . For these subjects we measured all Rome I GI symptoms and physician visits over the past 12 months , as well as neuroticism , anxiety , depression , and somatic distress . RESULTS : The response rate for the study was 72 % . The prevalence of any FGID was 34.6 % , and 62.1 % of these subjects had consulted a physician . There was considerable overlap of the FGIDs ( 19.2 % had more than two disorders ) . Independent predictors for an FGID diagnosis were neuroticism , somatic distress , anxiety , bowel habit disturbance , abdominal pain frequency , and increasing age . However , psychological morbidity did not independently discriminate between consulters and nonconsulters with an FGID . CONCLUSIONS : More than one third of the general population have one or more FGIDs . There seems to be a modest link between psychological morbidity and FGIDs , although other unknown factors seem to be more important in explaining health care seeking for these disorders Objectives : Irritable bowel syndrome is a multisymptom construct , with abdominal pain ( AP ) acting as the driving symptom of patient-reported severity . The Food and Drug Administration considers a > 30 % decrease in AP as satisfactory improvement , but this has not been vali date d in children . We investigated the correspondence of 2 measures for AP assessment , ≥30 % improvement in AP and global assessment of improvement . Methods : Secondary analysis of data from 72 children who completed a r and omized clinical trial for abdominal pain – associated functional gastrointestinal disorders . Children completed daily assessment of AP intensity , functional disability inventory ( FDI ) , question regarding pain 's interference with activities , and 2 global assessment questions . We measured the extent to which ≥30 % improvement of AP and global assessment questions correlated with each other and with disability . Results : The global questions correlated with each other ( r = 0.74 ; P < 0.0001 ) and with a ≥30 % improvement in AP ( P < 0.01 ) . Global outcomes were satisfaction with treatment was inversely related to the child 's report of interference with activities ( P < 0.01 ) and symptom relief was positively associated with ≥30 % improvement in FDI scores ( P < 0.009 ) . A 30 % change in FDI scores was associated with global questions of symptom relief ( P = 0.009 ) but not with satisfaction with treatment ( P = 0.07 ) . The association of AP improvement with interference with activities ( P = 0.14 ) or change in FDI scores ( P = 0.27 ) did not reach significance . Conclusions : Currently used global assessment s are significantly associated with decreased pain intensity , decreased interference with daily activities , and a ≥30 % change in FDI scores , whereas recommended 30 % improvement in pain intensity is not as comprehensive AIM To assess the efficacy of glucomannan ( GNN ) as the sole treatment for abdominal pain-related functional gastrointestinal disorders ( FGIDs ) . METHODS We conducted a double-blind , placebo-controlled , r and omized trial . Patients were recruited among children referred to the Department of Paediatrics , Medical University of Warsaw . Included in the study were children aged 7 - 17 years with abdominal pain-related FGIDs classified according to the Rome III diagnostic criteria . The children were r and omly assigned to receive GNN , a polysaccharide of 1,4-D-glucose and D-mannose , a soluble fiber from the Japanese Konjac plant , at a dosage of 2.52 g/d ( 1 sachet of 1.26 g 2 times a day ) , or a comparable placebo ( maltodextrin ) at the same dosage . The content of each sachet was dissolved in approximately 125 mL of fluid and was consumed twice daily for 4 wk . RESULTS Of the 89 eligible children , 84 ( 94 % ) completed the study . " No pain " and " treatment success " ( defined as no pain or a decrease ≥ 2/6 points on the FACES Pain Scale Revised ) were similar in the GNN ( n = 41 ) and placebo ( n = 43 ) groups [ no pain ( 12/41 vs 6/43 , respectively ; RR = 2.1 , 95%CI : 0.87 - 5.07 ) as well as treatment success ( 23/41 vs 20/43 ; RR = 1.2 , 95%CI : 0.79 - 1.83 ) ] . No significant differences between the groups were observed in the secondary outcomes , such as abdominal cramps , abdominal bloating/gassiness , episodes of nausea or vomiting , or a changed in stool consistency . GNN demonstrated no significant influence on the number of children requiring rescue therapy , school absenteeism , or daily activities . CONCLUSION In our setting , GNN , as dosed in this study , was no more effective than the placebo in achieving therapeutic success in the management of FGIDs in children OBJECTIVES To conduct a pilot study examining whether adding biofeedback-assisted relaxation training ( BART ) to medication treatment results in better clinical outcomes than medication treatment alone for children with functional dyspepsia ( FD ) associated with duodenal eosinophilia , a subgroup of children with recurrent abdominal pain . METHODS Twenty children were r and omly assigned to receive a st and ardized medication treatment or medication plus 10 sessions of BART . Children and parents completed psychosocial functioning and quality of life measures at baseline , posttreatment , and 6 months . Children rated pain daily via PDA . Physicians provided biweekly assessment s of clinical improvement . RESULTS Children receiving medication plus BART demonstrated better outcomes on pain intensity , duration of pain episodes , and clinical improvement than children receiving medication alone . CONCLUSIONS BART is a promising adjunctive treatment for pediatric FD associated with duodenal eosinophilia . Electronic daily diaries appear to be a useful approach to assessing changes in self-reported pain ratings in this population Background and Objectives : Chronic abdominal pain ( CAP ) in children may be a precursor to irritable bowel syndrome ( IBS ) in adults . The prevalence of abnormal lactulose breath tests ( LBT ) suggesting small intestinal bacterial overgrowth ( SIBO ) has been reported as 91 % in children with CAP and 35 % in healthy controls . In addition , patients with IBS with SIBO who responded to nonabsorbable antibiotic treatment with normalization of LBT reported 75 % global improvement in symptoms . The aim of the study was to test whether treatment with a nonabsorbable antibiotic may reduce symptoms in children with CAP . Methods : Seventy-five children ages 8 to 18 years with CAP based on Rome II criteria were enrolled . Subjects underwent baseline LBT and completed symptom-based question naires . They were then r and omized in a 2:1 , double-blind fashion to receive a 10-day course of 550 mg of rifaximin or placebo 3 times per day ( t.i.d . ) . LBT and question naires were repeated 2 weeks after treatment . Results : Forty-nine children received rifaximin and 26 received placebo . There were no differences in demographics between groups . Ninety-four percent who received rifaximin and 92 % who received placebo had abnormal baseline LBT , suggesting SIBO ( not significant [ NS ] ) . There was no significant difference in symptom improvement between groups ; however , only 20 % of children treated with rifaximin achieved a normalized repeat LBT , demonstrating successful treatment of SIBO . Conclusions : Similar to adults with IBS , the prevalence of abnormal LBT suggesting SIBO in children with CAP is high ; however , treatment with 10 days of rifaximin has low efficacy in normalizing LBT in this group . Additional studies are needed to determine whether a treatment approach with higher efficacy would lead to improvement in children with CAP |
2,237 | 26,242,225 | Smoking also yields cost savings in pension payments from the premature death of smokers .
3 .
The use of pharmacotherapies such as varenicline , NRT , and Bupropion , when combined with GP counseling or other behavioral treatment interventions ( such as proactive telephone counseling and Web-based delivery ) , is both clinical ly effective and cost effective to primary health care providers .
5 .
Price-based policy measures such as increase in tobacco taxes are unarguably the most effective means of reducing the consumption of tobacco .
6 .
Smoking cessation classes are known to be most effective among community-based measures , as they could lead to a quit rate of up to 35 % , but they usually incur higher costs than other measures such as self-help quit-smoking kits .
7 .
Advertising media , telecommunications , and other technology-based interventions ( such as TV , radio , print , telephone , the Internet , PC , and other electronic media ) usually have positive synergistic effects in reducing smoking prevalence especially when combined to deliver smoking cessation messages and counseling support .
9 .
Implementing smoke-free workplaces would also produce myriads of new quitters and reduce the amount of cigarette consumption , leading to cost savings in direct medical costs to primary health care providers .
Workplace interventions are , however , likely to yield far greater economic benefits over the long term , as reduced prevalence will lead to a healthier and more productive workforce .
Conclusions We conclude that the direct costs and externalities to society of smoking far outweigh any benefits that might be accruable at least when considered from the perspective of socially desirable outcomes ( ie , in terms of a healthy population and a productive workforce ) .
However , on the balance of probabilities , most of the cessation measures review ed have not only proved effective but also cost effective in delivering the much desired cost savings and net gains to individuals and primary health care providers | Background Tobacco smoking is the cause of many preventable diseases and premature deaths in the UK and around the world .
It poses enormous health- and non-health-related costs to the affected individuals , employers , and the society at large .
The World Health Organization ( WHO ) estimates that , globally , smoking causes over US$ 500 billion in economic damage each year .
Objectives This paper examines global and UK evidence on the economic impact of smoking prevalence and evaluates the effectiveness and cost effectiveness of smoking cessation measures .
The costs of smoking can be classified into direct , indirect , and intangible costs .
About 15 % of the aggregate health care expenditure in high-income countries can be attributed to smoking .
In the US , the proportion of health care expenditure attributable to smoking ranges between 6 % and 18 % across different states .
In the UK , the direct costs of smoking to the NHS have been estimated at between £ 2.7 billion and £ 5.2 billion , which is equivalent to around 5 % of the total NHS budget each year .
As part of the indirect ( non-health-related ) costs of smoking , the total productivity losses caused by smoking each year in the US have been estimated at US$ 151 billion .
However , the outcomes on the cost effectiveness of TMT-based measures have been inconsistent , and this made it difficult to attribute results to specific media . | BACKGROUND The aim of this study was to evaluate and compare the cost-effectiveness of varenicline with nicotine replacement therapy ( NRT ) for smoking cessation in four European countries ( Belgium , France , Sweden and the UK ) . METHODS Markov simulations , using the Benefits of Smoking Cessation on Outcomes ( BENESCO ) model , were performed . We simulated the incidence of four smoking-related morbidities : lung cancer , chronic obstructive pulmonary disease , coronary heart disease and stroke . The model computes quality -adjusted life-years gained and incremental cost-effectiveness ratios . Incremental cost-utility ratios were calculated , adopting a lifetime perspective . Efficacy data were obtained from a r and omized open-label trial : Week 52 continuous abstinence rates were 26.1 % for varenicline and 20.3 % for NRT . RESULTS The analyses imply that for countries analysed , smoking cessation using varenicline versus NRT was associated with reduced smoking-related morbidity and mortality . The number of morbidities avoided , per 1000 smokers attempting to quit , ranged from 9.7 in Belgium to 6.5 in the UK . The number of quality -adjusted life-years gained , per 1000 smokers , was 23 ( Belgium ) ; 19.5 ( France ) ; 29.9 ( Sweden ) ; and 23.7 ( UK ) . In all base-case simulations ( except France ) , varenicline dominated ( more effective and cost saving ) NRT regarding costs per quality -adjusted life-year gained ; for France the incremental cost-effectiveness ratio was 2803 . CONCLUSION This cost-effectiveness analysis demonstrated that since varenicline treatment was more effective , the result was increased healthcare cost savings in Belgium , Sweden and the UK . Our results suggest that funding varenicline as a smoking cessation aid is justifiable from a healthcare re source allocation perspective Introduction : School-based smoking prevention programmes can be effective , but evidence on cost-effectiveness is lacking . We conducted a cost-effectiveness analysis of a school-based “ peer-led ” intervention . Methods : We evaluated the ASSIST ( A Stop Smoking In Schools Trial ) programme in a cluster r and omized controlled trial . The ASSIST programme trained students to act as peer supporters during informal interactions to encourage their peers not to smoke . Fifty-nine secondary schools in Engl and and Wales were r and omized to receive the ASSIST programme or usual smoking education . Ten thous and seven hundred and thirty students aged 12–13 years attended participating schools . Previous work has demonstrated that the ASSIST programme achieved a 2.1 % ( 95 % CI = 0%–4.2 % ) reduction in smoking prevalence . We evaluated the public sector cost , prevalence of weekly smoking , and cost per additional student not smoking at 24 months . Results : The ASSIST programme cost of £ 32 ( 95 % CI = £ 29.70–£33.80 ) per student . The incremental cost per student not smoking at 2 years was £ 1,500 ( 95 % CI = £ 669–£9,947 ) . Students in intervention schools were less likely to believe that they would be a smoker at age 16 years ( odds ratio [ OR ] = 0.80 ; 95 % CI = 0.66–0.96 ) . Conclusions : A peer-led intervention reduced smoking among adolescents at a modest cost . The intervention is cost-effective under realistic assumptions regarding the extent to which reductions in adolescent smoking lead to lower smoking prevalence and /or earlier smoking cessation in adulthood . The annual cost of extending the intervention to Year 8 students in all U.K. schools would be in the region of £ 38 million and could result in 20,400 fewer adolescent smokers OBJECTIVES To : evaluate the impact of smoking status on objective productivity and absenteeism measures ; evaluate the impact of smoking status on subjective measures of productivity ; and assess the correlation between subjective and objective productivity measures . DESIGN Prospect i ve cohort study in a workplace environment . SUBJECTS Approximately 300 employees ( 100 each of former , current , and never smokers ) at a reservation office of a large US airline . MAIN OUTCOME MEASURES Objective productivity and absenteeism data were supplied by the employer . Subjective assessment s of productivity were collected using a self report instrument , the Health and Work Question naire ( HWQ ) . RESULTS Current smokers had significantly greater absenteeism than did never smokers , with former smokers having intermediate values ; among former smokers , absenteeism showed a significant decline with years following cessation . Former smokers showed an increase in seven of 10 objective productivity measures as compared to current smokers , with a mean increase of 4.5 % . While objective productivity measures for former smokers decreased compared to measures for current smokers during the first year following cessation , values for former smokers were greater than those for current smokers by 1–4 years following cessation . Subjective assessment s of “ productivity evaluation by others ” and “ personal life satisfaction ” showed significant trends with highest values for never smokers , lowest for current smokers , and intermediate for former smokers . CONCLUSIONS Workplace productivity is increased and absenteeism is decreased among former smokers as compared to current smokers . Productivity among former smokers increases over time toward values seen among never smokers . Subjective measures of productivity provide indications of novel ways of productivity assessment that are sensitive to smoking status Background Although effective smoking cessation interventions exist , information is limited about their cost-effectiveness and cost-utility . Objective To assess the cost-effectiveness and cost-utility of an Internet-based multiple computer-tailored smoking cessation program and tailored counseling by practice nurses working in Dutch general practice s compared with an Internet-based multiple computer-tailored program only and care as usual . Methods The economic evaluation was embedded in a r and omized controlled trial , for which 91 practice nurses recruited 414 eligible smokers . Smokers were r and omized to receive multiple tailoring and counseling ( n=163 ) , multiple tailoring only ( n=132 ) , or usual care ( n=119 ) . Self-reported cost and quality of life were assessed during a 12-month follow-up period . Prolonged abstinence and 24-hour and 7-day point prevalence abstinence were assessed at 12-month follow-up . The trial-based economic evaluation was conducted from a societal perspective . Uncertainty was accounted for by bootstrapping ( 1000 times ) and sensitivity analyses . Results No significant differences were found between the intervention arms with regard to baseline characteristics or effects on abstinence , quality of life , and addiction level . However , participants in the multiple tailoring and counseling group reported significantly more annual health care – related costs than participants in the usual care group . Cost-effectiveness analysis , using prolonged abstinence as the outcome measure , showed that the mere multiple computer-tailored program had the highest probability of being cost-effective . Compared with usual care , in this group € 5100 had to be paid for each additional abstinent participant . With regard to cost-utility analyses , using quality of life as the outcome measure , usual care was probably most efficient . Conclusions To our knowledge , this was the first study to determine the cost-effectiveness and cost-utility of an Internet-based smoking cessation program with and without counseling by a practice nurse . Although the Internet-based multiple computer-tailored program seemed to be the most cost-effective treatment , the cost-utility was probably highest for care as usual . However , to ease the interpretation of cost-effectiveness results , future research should aim at identifying an acceptable cutoff point for the willingness to pay per abstinent participant PURPOSE To evaluate the incremental effectiveness and cost-effectiveness of a staged-based , computerized smoking cessation intervention relative to st and ard care in an urban managed care network of primary care physicians . DESIGN Decision-analytic model based on results of a r and omized clinical trial . METHODOLOGY Patient outcomes and cost estimates were derived from clinical trial data . Effectiveness was measured in terms of 7-day point-prevalence abstinence at 6 months post-intervention . Quality -adjusted life years ( QALYs ) and cost-effectiveness ( CE ) were calculated , with CE measured as cost per patient per life year saved and per quality -adjusted life years saved . CE estimates were adjusted to account for partial behavior change as measured in terms of progression in stage of readiness to quit . Sensitivity analyses were conducted to evaluate the robustness of key model assumptions . PRINCIPAL FINDINGS Intervention patients were 1.77 times more likely to be smoke-free at 6 months follow-up than those in st and ard care ( p=.078 ) . The intervention generated an additional 3.24 quitters per year . Annualized incremental costs were $ 5,570 per primary care practice , and $ 40.83 per smoker . The mean incremental cost-effectiveness ratio was $ 1,174 per life year saved ( $ 869 per QALY ) . When the intervention impact on progression in stage of readiness to quit was also considered , the mean incremental cost-effectiveness ratio declined to $ 999 per life year saved ( $ 739 per QALY ) . CONCLUSIONS From a physician 's practice perspective , the stage-based computer tailored intervention was cost-effective relative to st and ard care . Incorporation of partial behavior change into the model further enhanced favorability of the cost-effectiveness ratio Introduction : An employer-based cost-benefit analysis for varenicline versus bupropion was conducted using clinical outcomes from a recently published trial . Methods : A decision tree model was developed based on the net benefit of treatment to produce a nonsmoker at 1 year . Sensitivity analyses were conducted based on quit rates with placebo and varenicline and the cost of varenicline . Results : Estimated 12-month employer cost savings per non-smoking employee were $ 540.60 for varenicline , $ 269.80 for bupropion SR generic , $ 150.80 for bupropion SR br and , and $ 81.80 for placebo . Varenicline was more cost beneficial than placebo , which had quit rates of 16.9 % or less . The quit rate with varenicline would have to be ≤16.9 % to lose cost benefit over bupropion SR generic . Conclusions : The economic benefit of varenicline is improved over bupropion , despite the increased initial cost of varenicline There is a lack of evidence of the relative cost-effectiveness of proactive telephone counseling ( PTC ) and Web-based delivery of smoking cessation services in conjunction with pharmacotherapy . We calculated the differential cost-effectiveness of three behavioral smoking cessation modalities with varenicline treatment in a r and omized trial of current smokers from a large health system . Eligible participants were r and omized to one of three smoking cessation interventions : Web-based counseling ( n = 401 ) , PTC ( n = 402 ) , or combined PTC-Web counseling ( n = 399 ) . All participants received a st and ard 12-week course of varenicline . The primary outcome was a 7-day point prevalent nonsmoking at the 6 month follow-up . The Web intervention was the least expensive followed by the PTC and PTC-Web groups . Costs per additional 6-month nonsmoker and per additional lifetime quitter were $ 1,278 and $ 2,601 for Web , $ 1,472 and $ 2,995 for PTC , and $ 1,617 and $ 3,291 for PTC-Web . Cost per life-year ( LY ) and quality -adjusted life-year ( QALY ) saved were $ 1,148 and $ 1,136 for Web , $ 1,320 and $ 1,308 for PTC , and $ 1,450 and $ 1,437 for PTC-Web . Based on the cost per LY and QALY saved , these interventions are among the most cost-effective life-saving medical treatments . Web , PTC , and combined PTC-Web treatments were all highly cost-effective , with the Web treatment being marginally more cost-effective than the PTC or combined PTC-Web treatments BACKGROUND Employers have responded to new regulations on the effects of passive smoking by introducing a range of workplace policies . Few policies include provision of smoking cessation intervention . OBJECTIVE To estimate the cost to employers of smoking in the workplace in Scotl and to illustrate the potential gains from smoking cessation provision . Costs vary with type of smoking policy in place ; therefore , to estimate these costs results from a survey were combined with evidence drawn from a literature review . STUDY DESIGN A telephone survey of 200 Scottish workplaces , based on a stratified r and om sample of workplaces with 50 or more employees , was conducted in 1996 . Additional evidence was compiled from a review of the literature of smoking related costs and specific smoking related effects . RESULTS 167 completed responses were received , of which 156 employers ( 93 % ) operated a smoking policy , 57 ( 34 % ) operated smoke free buildings , and 89 ( 53 % ) restricted smoking to a “ smoke room ” . The research literature shows absenteeism to be higher among smokers when compared to non-smokers . The estimated cost of smoking related absence in Scotl and is £ 40 million per annum . Total productivity losses are estimated at approximately £ 450 million per annum . In addition , the re source cost in terms of losses from fires caused by smoking material s is estimated at approximately £ 4 million per annum . In addition , there are costs from smoking related deaths and smoking related damage to premises . CONCLUSION This study shows how smoking cessation interventions in the workplace can yield positive cost savings for employers , result ing in gains in productivity and workplace attendance which may outweigh the cost of any smoking cessation programme BACKGROUND Smoking cessation should be encouraged in order to increase life expectancy and reduce smoking-related healthcare costs . Results of a r and omised trial suggested that reimbursing the costs of smoking cessation treatment ( SCT ) may lead to an increased use of SCT and an increased number of quitters versus no reimbursement . OBJECTIVE To assess whether reimbursement for SCT is a cost-effective intervention ( from the Dutch societal perspective ) , we calculated the incremental costs per quitter and extrapolated this outcome to incremental costs per QALY saved versus no reimbursement . METHODS In the reimbursement trial , 1266 Dutch smokers were r and omly assigned to the intervention or control group using a r and omised double consent design . Reimbursement for SCT was offered to the intervention group for a period of 6 months . No reimbursement was offered to the control group . Prolonged abstinence from smoking was determined 6 months after the end of the reimbursement period . The QALYs gained from quitting were calculated until 80 years of age using data from the US . Costs ( year 2002 values ) were determined from the societal perspective during the reimbursement period ( May-November 2002 ) . Benefits were discounted at 4 % per annum . The uncertainty of the incremental cost-effectiveness ratios was estimated using non-parametric bootstrapping . RESULTS Eighteen participants in the control group ( 2.8 % ) and 35 participants in the intervention group ( 5.5 % ) successfully quit smoking . The costs per participant were 291 euro and 322 euro , respectively . If society is willing to pay 1000 euro or 10,000 euro for an additional 12-month quitter , the probability that reimbursement for SCT would be cost effective was 50 % or 95 % , respectively . If society is willing to pay 18,000 euro for a QALY , the probability that reimbursement for SCT would be cost effective was 95 % . However , the external validity of the extrapolation from quitters to QALYs is uncertain and several assumptions had to be made . CONCLUSION Reimbursement for SCT may be cost effective if Dutch society is willing to pay 10,000 euro for an additional quitter or 18,000 euro for a QALY BACKGROUND The 1998 UK government White Paper Smoking Kills emphasises that normal practice should be for general practitioners ( GPs ) , practice nurses , and others to offer advice and support to smokers in their efforts to stop . However , GPs are not allowed to write NHS prescriptions for nicotine-replacement therapy , even though this is the only effective pharmaceutical treatment available in the UK . We estimated the cost-effectiveness , for the NHS , of allowing GPs to prescribe transdermal nicotine patches for up to 12 weeks . METHODS We used data from a r and omised , placebo-controlled efficacy trial of nicotine patches and a survey of associated re source use in 30 GP surgeries in 15 English counties . We calculated the health benefit of nicotine-patch treatment in number of life years that would be saved by stopping smoking at various ages , and used an abstinence-contingent treatment model to calculate the incremental cost per life year saved by GP counselling with nicotine-patch treatment over GP counselling alone . Cost effectiveness was assessed on the basis that GPs would provide repeat NHS prescriptions for up to 12 weeks if the treatment was proving successful . FINDINGS If GPs were allowed to prescribe transdermal nicotine patches on the NHS , for up to 12 weeks , the incremental cost per life year saved would be : Pound Sterling 398 per person younger than 35 years ; Pound Sterling 345 for those aged 35 - 44 years ; Pound Sterling 432 for those aged 45 - 54 years ; and Pound Sterling 785 for those aged 55 - 65 years . INTERPRETATION The low cost per life year saved would make GP intervention against smoking a cost-effective life-saving treatment . The priniciples of the government White Paper could be cost-effectively extended into general practice to reduce smoking and smoking-related illnesses Tobacco smoking is a risk factor for cancer , respiratory disease , and cardiovascular disease . It is estimated that 19 % of Canadians ( approximately 5.2 million ) aged 15 years and older were smokers in 2007.1 Each year , approximately 45,000 Canadians die from smoking.2 Significantly , one-third of Canadian smokers aged 15 years or older express an intention to quit in the next 30 days.3 Nicotine , the addictive chemical component of tobacco products that attracts smokers , has consequences for personal and community health . Smoking is an addiction . Although many smokers report that they quit unaided , most smokers who try to quit without smoking cessation aids are unsuccessful in the long term . In the US and UK , 70 % of smokers intend to quit every year , 45 % try to quit , and less than 5 % are successful.4,5 The rate of relapse is high among smokers who quit without treatment . The proportion of smokers who can achieve abstinence for at least one week is 25 % to 51 % , 10 % to 20 % for those able to do it for at least three months , and only 3 % to 5 % for those able to abstain for six months.6 There are many prescribed pharmacotherapies for smoking cessation , including nicotine replacement products , bupropion , and varenicline . Smoking cessation programs often combine drug treatment and behavioural support ( such as psychological interventions , telephone support , and self-help ) . Objective The objective of the report was to : Compare the pharmacological agents ( drug-based smoking cessation aids ) to determine which of these works best ( clinical effectiveness ) at six months and 12 months after patients attempt to quit smoking . Perform an economic analysis to determine which smoking cessation therapy was the most cost-effective for patients , drug plans , and the Canadian health care system . Methods To compare pharmacological agents with or without behavioural support programs for smoking cessation in adults , a systematic review with meta-analyses and an economic evaluation were carried out . A budget impact analysis and an examination of current public funding and planning issues were also performed . For the clinical review , a total of 155 articles ( from August 1982 to June 2009 ) describing 143 trials were selected for inclusion in the clinical analyses . To meet the inclusion criteria , r and omized controlled trials ( RCTs ) must have reported biochemically vali date d measures of smoking abstinence from the study start date or from the target quit date of at least six months . Analyses were conducted using a Bayesian r and om effects model for mixed treatment comparisons meta- analysis . Continuous abstinence rates ( patients have not smoked at all since quitting ) and point prevalence abstinence rates ( patients have not smoked in the past seven days ) were analyzed separately . For the economic analysis , a decision-analytic model was constructed to assess the cost-effectiveness ( cost per additional quitter and cost per life-year gained ; cost per quality -adjusted life-year [ QALY ] gained ) of nicotine replacement therapy ( NRT ) , bupropion , and varenicline compared with no pharmacologic treatment , from the perspective of a publicly funded health care system . For the base case , the general population ( stratified by age and gender ) motivated to quit smoking was considered . Treatment strategies included one-time cessation interventions of NRT , bupropion , varenicline , and no pharmacologic treatment ; it was assumed that all patients received the same level of behavioural support . Budget impact analyses were conducted by comparing current utilization patterns of NRT , bupropion , and varenicline , with alternative scenarios reflecting the prescription patterns of these therapies OBJECTIVE To evaluate the costs and outcomes associated with the Health Education Board for Scotl and 's general public anti-smoking campaign during the developmental stage and its first year of operation . DESIGN Cost information collected retrospectively was combined with prospect ively collected effectiveness data . SUBJECTS A panel of 970 adults were recruited from a 1-in-10 r and om sample of adult callers to the telephone helpline ( Smokeline ) . Those who smoked were subsequently interviewed at three weeks , six months , and one year follow up . Information on smoking status at one year and time spent as a non-smoker was available for 587 members of the panel . MAIN OUTCOME MEASURES Intermediate outcomes in the follow-up sample included a point prevalence and period prevalence measure of smoking cessation . Long-term outcomes were measured in terms of predicted reductions in mortality as a consequence of smoking cessation . RESULTS At the 12-month point , 9.88 % of individuals in the follow-up sample reported themselves as non-smokers and as having given up for at least six months in the previous year . Estimates of the cost per life-year saved as a result of the campaign range from 304 pounds sterling to 656 pounds sterling . CONCLUSIONS Provided that the benefits of smoking cessation are broadly accurate , and the assumed level of quitting can be directly attributed to Smokeline , then this mass media-led anti-smoking campaign appears to have been cost effective 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 |
2,238 | 27,542,161 | There was considerable variability between the interventions , but they were all multifactorial , with components such as nutritional education , physical activity , family support and psychological therapy .
The number of contacts with subjects during the course of the intervention was a predictor of treatment efficacy when the groups were compared .
Conclusions Multidisciplinary interventions including family support and guided behavior modification appear to be effective methods of reducing BMI in overweight and obese adolescents | Purpose To determine what factors contribute to the efficacy of non-drug treatments design ed to promote weight loss in overweight and obese adolescents . | BACKGROUND AND OBJECTIVE : Most clinic-based weight control treatments for youth have been design ed for preadolescent children by using family-based care . However , as adolescents become more autonomous and less motivated by parental influence , this strategy may be less appropriate . This study evaluated a primary care – based , multicomponent lifestyle intervention specifically tailored for overweight adolescent females . METHODS : Adolescent girls ( N = 208 ) 12 to 17 years of age ( mean ± SD : 14.1 ± 1.4 years ) , with a mean ± SD BMI percentile of 97.09 ± 2.27 , were assigned r and omly to the intervention or usual care control group . The gender and developmentally tailored intervention included a focus on adoptable healthy lifestyle behaviors and was reinforced by ongoing feedback from the teen ’s primary care physician . Of those r and omized , 195 ( 94 % ) completed the 6-month posttreatment assessment , and 173 ( 83 % ) completed the 12-month follow-up . The primary outcome was reduction in BMI z score . RESULTS : The decrease in BMI z score over time was significantly greater for intervention participants compared with usual care participants ( −0.15 in BMI z score among intervention participants compared with −0.08 among usual care participants ; P = .012 ) . The 2 groups did not differ in secondary metabolic or psychosocial outcomes . Compared with usual care , intervention participants reported less reduction in frequency of family meals and less fast-food intake . CONCLUSIONS : A 5-month , medium-intensity , primary care – based , multicomponent behavioral intervention was associated with significant and sustained decreases in BMI z scores among obese adolescent girls compared with those receiving usual care BACKGROUND Cognitive behavioral therapy ( CBT ) teaches behavioral and cognitive strategies that focus on achieving and maintaining lifestyle changes . OBJECTIVE We examined the effectiveness of a CBT program ( CHOOSE HEALTH ) for improving body composition , diet , and physical activity in overweight and obese adolescents . DESIGN Adolescents [ 16 male , 31 female ; aged 14.5 + /- 1.6 y ; body mass index ( BMI ; in kg/m(2 ) ) 30.9 + /- 4.2 ] were block-matched into 2 groups by age , sex , Tanner stage , BMI , and hip and waist circumferences and were r and omly assigned to CBT or no treatment ( control ) . CBT consisted of 10 weekly sessions , followed by 5 fortnightly telephone sessions . RESULTS Compared with the control , over 20 wk , CBT improved ( significant group x time interactions ) BMI ( CBT , -1.3 + /- 0.4 ; control , 0.3 + /- 0.3 ; P = 0.007 ) , weight ( CBT , -1.9 + /- 1.0 kg ; control , 3.8 + /- 0.9 kg ; P = 0.001 ) , body fat ( CBT , -1.5 + /- 0.9 kg ; control , 2.3 + /- 1.0 kg ; P = 0.001 ) , and abdominal fat ( CBT , -124.0 + /- 46.9 g ; control , 50.1 + /- 53.5 g ; P = 0.008 ) . CBT showed a greater reduction in intake of sugared soft drinks as a percentage of total energy ( CBT , -4.0 + /- 0.9 % ; control , -0.3 + /- 0.9 % ; P = 0.005 for group x time interaction ) , which was related to reductions in weight ( r = 0.48 , P = 0.04 ) , BMI ( r = 0.53 , P = 0.02 ) , and waist circumference ( r = 0.54 , P = 0.02 ) . Physical activity did not change significantly . CONCLUSIONS A 10-wk CBT program followed by 10 wk of fortnightly phone contact improved body composition in overweight and obese adolescents . Changes in soft drink consumption may have contributed to this benefit OBJECTIVE A r and omized controlled trial tested the efficacy of an internet-based lifestyle behavior modification program for African-American girls over a 2-year period of intervention . RESEARCH METHODS AND PROCEDURES Fifty-seven overweight ( mean BMI percentile , 98.3 ) African-American girls ( mean age , 13.2 years ) were r and omly assigned to an interactive behavioral internet program or an internet health education program , the control condition . Overweight parents were also participants in the study . Forty adolescent-parent dyads ( 70 % ) completed the 2-year trial . Outcome data including BMI , body weight , body composition , and weight loss behaviors were collected at baseline and at 6-month intervals . A computer server tracked use of the web sites . RESULTS An intention-to-treat statistical approach was used , with the last observation carried forward . In comparison with the control condition , adolescents in the behavioral program lost more mean body fat ( BF ) ( -1.12 + /- 0.47 % vs. 0.43 + /- 0.47 % BF , p < 0.05 ) , and parents in the behavioral program lost significantly more mean body weight ( -2.43 + /- 0.66 vs. -0.35 + /- 0.64 kg , p < 0.05 ) during the first 6 months . This weight loss was regained over the next 18 months . After 2 years , differences in fat for adolescents ( -0.08 + /- 0.71 % vs. 0.84 + /- 0.72 % BF ) and weight for parents ( -1.1 + /- 0.91 vs. -0.60 + /- 0.89 kg ) did not differ between the behavioral and control programs . DISCUSSION An internet-based weight management program for African-American adolescent girls and their parents result ed in weight loss during the first 6 months but did not yield long-term loss due to reduced use of the web site over time Lifestyle modification programs ( LMP ) for weight loss in adolescents with obesity are effective but not available . Primary care may be a setting for reaching more adolescents . Two models of LMP for use in primary care were examined . Adolescents and caregivers enrolled in a 1-year r and omized trial comparing Group LMP with Self-Guided LMP . All participants ( N = 169 ) received the same treatment recommendations and met with a health coach six times in clinic . Group LMP participants had an additional 17 group sessions ; those in Self-Guided LMP followed the remainder of the program at home with parental support . The primary outcome was percentage change in initial body mass index . The mean ( SE ) 1.31 % ( 0.95 % ) reduction in Group LMP did not differ significantly from the 1.17 % ( 0.99 % ) decrease in the Self-Guided LMP ( p = 0.92 ) . Both treatments were significantly effective in reducing body mass index . Given its brevity , the Self-Guided LMP offers an innovative approach for primary care Using self-determination theory ( SDT ) as an explanatory framework , this r and omised-controlled study evaluates the effect of a motivational interviewing (MI)-based intervention as an addition to a st and ard weight loss programme ( SWLP ) on physical activity ( PA ) practice in obese adolescents over a six-month period . Fifty-four obese adolescents ( mean age = 13 years , mean BMI = 29.57 kg/m² ) were r and omly assigned to an SWLP group ( n = 28 ) or SWLP + MI group ( n = 26 ) . Both groups received two SWLP sessions , supplemented for the SWLP + MI group , by six MI sessions . Perceived autonomy support , perceived competence , motivational regulations , PA and BMI were assessed at baseline , three and six months ( i.e. the end of the programme ) . MLM analyses revealed that compared to SWLP , the SWLP + MI group had a greater BMI decrease and a greater PA practice increase over time . Moreover , the SWLP + MI group reported greater autonomy support from medical staff at the end of the programme , greater increase in integrated and identified regulations and a stronger decrease in amotivation . MI appears as an efficient counselling method as an addition to an SWLP to promote PA in the context of pediatric obesity OBJECTIVE To evaluate the efficacy of Motivational Interviewing ( MI ) as an intervention for promoting self-efficacy and weight loss in a sample of overweight and obese youth . METHODS / Design 40 participants ( aged 10 - 18 years ) were r and omly assigned to control ( social skills training ) or treatment ( MI ) group . Both groups received individual therapy ( ~30 min/month ) in addition to usual care of diet/exercise counseling . Pre- and post- ( at 6 months follow-up ) variables included measures of self-efficacy and anthropometrics . RESULTS Although significant between-group differences were not found , individuals in the MI group attended more sessions . Overall , participants in both groups showed significant increases in self-efficacy and a trend of decreased body mass index z-scores . CONCLUSIONS Health benefits from participation in individual therapy may have been accrued ; however , specific benefits attributable to MI were limited . Findings suggest that more than one type of counseling intervention ( i.e. , MI and social skills training ) may be beneficial when providing integrative treatment for obese youth OBJECTIVE : This study examined the 24-month outcomes of a r and omized controlled trial of a group-based behavioral weight control ( BWC ) program combined with either activity-based peer intervention or aerobic exercise . METHODS : At baseline , 118 obese adolescents ( 68 % female ; BMI = 31.41 ± 3.33 ) ages 13 to 16 years ( mean = 14.33 ; SD = 1.02 ) were r and omized to receive 1 of 2 weight loss interventions . Both interventions received the same 16-week group-based cognitive-behavioral treatment , combined with either aerobic exercise or peer-based adventure therapy . Eighty-nine adolescents ( 75 % of original sample ) completed the 24-month follow-up . Anthropometric and psychosocial measures were obtained at baseline , at the end of the 16-week intervention , and at 12 and 24 months following r and omization . RESULTS : An intent-to-treat mixed factor analysis of variance indicated a significant effect for time on both percent over 50th percentile BMI for age and gender and st and ardized BMI score , with no differences by intervention group . Post hoc comparisons showed a significant decrease in percent overweight at 4 months ( end of treatment ) , which was maintained at both 12- and 24-month follow-up visits . Significant improvements on several dimensions of self-concept were noted , with significant effects on physical appearance self-concept that were maintained through 24 months . CONCLUSIONS : Both BWC conditions were effective at maintaining reductions in adolescent obesity and improvements in physical appearance self-concept through 24-month follow-up . This study is one of the first to document long-term outcomes of BWC intervention among adolescents OBJECTIVE The aim was to evaluate the efficacy of a Family Weight School treatment based on family therapy in group meetings with adolescents with a high degree of obesity . METHODS Seventy-two obese adolescents aged 12 - 19 years old were referred to a childhood obesity center by pediatricians and school nurses and offered a Family Weight School therapy program in group meetings given by a multidisciplinary team . Intervention was compared with an untreated waiting list control group . Body mass index ( BMI ) and BMI z-scores were calculated before and after intervention . RESULTS Ninety percent of the intervention group completed the program ( 34 boys , 31 girls ; baseline age = 14.8 + /- 1.8 years [ mean + /- st and ard deviation , SD ] , BMI = 34 + /- 4.0 , BMI z-score = 3.3 + /- 0.4 ) . In the control group 10 boys and 13 girls ( baseline age = 14.3 + /- 1.6 , BMI = 34.1 + /- 4.8 , BMI z-score = 3.2 + /- 0.4 ) participated in the 1-year follow-up . Adolescents in the intervention group with initial BMI z-score < 3.5 ( n = 49 out of 65 , baseline mean age = 14.8 , mean BMI = 33.0 , mean BMI z-score = 3.1 ) , showed a significant decrease in BMI z-scores in both genders ( -0.09 + /- 0.04 , p = 0.039 ) compared with those in the control group with initial BMI z-score < 3.5 ( n = 17 out of 23 , mean baseline age = 14.1 , mean baseline BMI = 31.6 , mean baseline BMI z-score = 3.01 ) . No difference was found in adolescents with BMI z-scores > 3.5 . CONCLUSIONS Family Weight School treatment model might be suitable for adolescents with BMI z-score < 3.5 treated with a few sessions in a multidisciplinary program AIM This study evaluates the efficacy of the Choose Health program , a family-based cognitive behavioural lifestyle program targeting improved eating and activity habits , in improving body composition , cardiovascular fitness , eating and activity behaviours in overweight and obese adolescents . METHOD The sample comprised 29 male and 34 female overweight ( n = 15 ) or obese ( n = 48 ) adolescents aged 11.5 - 18.9 years ( M = 14.3 , SD = 1.9 ) . Participants were r and omly allocated to treatment or waitlist control conditions ; waitlist condition participants were offered treatment after 6 months . DEXA-derived and anthropometric measures of body composition ; laboratory-based cycle ergometer and field-assessed cardiovascular fitness data ; objective and self-report physical activity measures ; and self-report measures of eating habits and 7-day weighed food diaries were used to assess treatment outcome . Adherence to treatment protocol s was high . RESULTS Treatment result ed in significant ( p < .05 ) and sustained improvements in a range of body composition ( body fat , percent body fat , lean mass ) and anthropometric measures ( weight , BMI , BMI -for-age z-score and percentiles ) . Minimal improvements were seen in cardiovascular fitness . Similar results were obtained in completer and intention-to-treat analysis . Poor adherence to assessment protocol s limits conclusions that can be drawn from physical activity and dietary data . CONCLUSIONS Participation in the Choose Health program result ed in significant improvement in body composition . Longer-term follow up is required to determine the durability of intervention effects . Alternative approaches to the measurement of diet and physical activity may be required for adolescents Adolescents Committed to Improvement of Nutrition and Physical Activity ( ACTION ) was undertaken to determine feasibility of a school-based health center ( SBHC ) weight management program . Two urban New Mexico SBHCs were r and omized to deliver ACTION or st and ard care . ACTION consisted of eight visits using motivational interviewing to improve eating and physical activity behavior . An educational nutrition and physical activity DVD for students and a clinician toolkit were created for use as menu of options . St and ard care consisted of one visit with the SBHC provider who prescribed recommendations for healthy weight . Sixty nondiabetic overweight/obese adolescents were enrolled . Measures included BMI percentile , waist circumference , insulin resistance by homeostasis model assessment ( HOMA-IR ) , blood pressure , triglycerides , and HDL-C levels . Pre- to postchanges for participants were compared between groups . Fifty-one students ( mean age 15 years , 62 % female , 75 % Hispanic ) completed pre- and post measures . ACTION students ( n = 28 ) had improvements in BMI percentile ( P = 0.04 ) and waist circumference ( P = 0.04 ) as compared with students receiving st and ard care ( n = 23 ) . No differences were found between the two groups in blood pressure , HOMA-IR , triglycerides , and HDL-C. The ACTION SBHC weight management program was feasible and demonstrated improved outcomes in BMI percentile and waist circumference PURPOSE This study evaluated 24-month outcomes of a school-based intensive lifestyle weight management program targeting overweight Mexican-American adolescents . METHODS We recruited a total of 71 adolescents ( 32 males ; 45.1 % ) between the ages of 10 and 14 years , at or above the 85th percentile for body mass index ( BMI ) . Participants were r and omized to a 6-month instructor-led intervention ( ILI ) or a self-help ( SH ) program . Both interventions were aim ed at modifying eating and physical activity behaviors using behavior modification strategies . We assessed changes in participants ' st and ardized BMI and BMI percentile at baseline , 1 , and 2 years . RESULTS Repeated- measures analyses showed that ILI participants showed significantly greater decreases in st and ardized BMI at 1 and 2 years ( F = 8.58 , p < .01 ; and F = 9.27 , p < .01 , respectively ) compared with SH controls . Similar results were found for changes in BMI and BMI percentile . At 2 years , the ILI condition decreased their average BMI percentile by 3.9 percentile points , compared to an increase of 1.6 percentile points in the SH condition . CONCLUSIONS A school-based intervention result ed in improved weight outcomes in overweight Mexican-American adolescents and results were maintained over 2 years Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists OBJECTIVE To conduct a pilot study design ed to measure the impact of a healthy lifestyle intervention with or without individualized mentorship on adiposity , metabolic profile , nutrition and physical activity in overweight teens . METHODS A total of 38 overweight adolescents ( body mass index above the 85th percentile ) 12 to 16 years of age , who were enrolled in a healthy lifestyle intervention program for six months , were r and omly assigned to a nonmentored or individualized mentored intervention . RESULTS For the entire cohort ( final n=32 ) , there was a nonstatistically significant reduction in mean ( ± SD ) body mass index z score ( 2.08±0.38 to 2.01±0.47 , P=0.07 ) and waist circumference ( 98±10 cm to 96±11 cm , P=0.08 ) , and significant improvements in high-density lipoprotein level ( 1.08±0.24 mmol/L to 1.20±0.26 mmol/L , P<0.001 ) , and low-density lipoprotein/high-density lipoprotein ratio ( 2.55±0.84 to 2.26±0.87 , P<0.001 ) from baseline to the end of the intervention . Subjects consumed fewer high-calorie foods ( 3.9±1.9 to 3.0±1.5 servings/day , P=0.01 ) and snacks ( 9.7±5.5 to 6.8±4.0 servings/day , P=0.02 ) , made fewer fast food restaurant visits ( 1.4±1.3 to 0.8±0.9 visits/week , P=0.02 ) , and had less screen time ( 8.3±3.8 to 6.9±3.6 h/day , P=0.01 ) . In addition , mentorship was found to be a feasible approach to supporting weight management in obese teens . Our study was underpowered to determine treatment effect , but promising modifications to lifestyle were observed despite the absence of statistically significant improvements in outcomes . CONCLUSIONS The healthy lifestyle intervention improved subjects ' lifestyles and lipid profiles , and the addition of mentorship in this context is feasible . A larger study with a longer intervention time is required to determine whether behavioural changes are associated with clinical improvement and to determine the role of mentorship in promoting lifestyle change AIM This paper is a report of a study conducted to evaluate the effects of behaviour modification on anthropometric indices and to explore if behaviour modification could improve eating behaviour in adolescents . BACKGROUND Obesity is currently the most important nutritional disease of children and adolescents . To date , several attempts to achieve weight loss in children have been made , but little is known about their effects on improving eating behaviours . METHOD Sixty obese adolescent girls participated in a behaviour modification program which was held for 16 weeks in 2007 . The participants were r and omly selected from two different schools and were assigned to an experimental and control group ( 30 participants each ) . Anthropometric indices and eating behaviours were assessed before and after the program . Eating behaviour was assessed using the Dutch Eating Behaviour Question naire . RESULT There were statistically significant differences in changes in body weight ( -2.75 kg vs. 0.62 kg ) , body mass index ( -1.07 kg/m(2 ) vs. 0.24 kg/m(2 ) ) and arm circumference ( -2.31 cm vs. 0.5 cm ) in the experimental group in contrast to controls ( P < 0.001 ) . There were also statistically significant differences in scores for eating behaviour , emotional eating ( 0.63 , 0.17 ) , external eating ( 0.99 , 0.05 ) and restrained eating ( 0.72 , 0.03 ) in the experimental vs. the control group respectively ( P < 0.001 ) . CONCLUSION Nurses , more than other healthcare professionals , can address obesity in adolescents and they should not concentrate solely on weight reduction , but also encourage children to acquire a healthy lifestyle 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 OBJECTIVES To assess the outcomes of the Loozit adolescent weight management intervention and to evaluate the effect of additional therapeutic contact 12 months into the program . DESIGN A 24-month , 2-arm r and omized controlled trial . Results at 12 months are presented . SETTING Community health center and children 's hospital in Sydney , Australia . PARTICIPANTS A total of 151 overweight or obese 13- to 16-year-olds . INTERVENTION In the first 2 months ( phase 1 ) , participants received 7 adolescent and parent weekly sessions focused on lifestyle modification . From 2 to 24 months ( phase 2 ) , adolescents attended booster sessions once every 3 months . During phase 2 , adolescents r and omized to the additional therapeutic contact arm also received telephone coaching and electronic communications once every 2 weeks . OUTCOME MEASURES Baseline to 12-month changes in body mass index z score and waist to height ratio ( primary outcomes ) and changes in metabolic , psychosocial , and behavioral variables . RESULTS Of 151 r and omized adolescents , 82.1 % completed 12-month follow-up . Intent-to-treat analyses showed significant reductions in mean body mass index z score ( -0.09 ; 95 % CI , -0.12 to -0.06 ) , waist to height ratio ( -0.02 ; 95 % CI , -0.03 to -0.01 ) , total cholesterol level ( -4 mg/dL ; 95 % CI , -8 to 0 mg/dL ; to convert to millimoles per liter , multiply by 0.0259 ) , and triglycerides level ( geometric mean , -80 mg/dL ; 95 % CI , -88 to -71 mg/dL ; to convert to millimoles per liter , multiply by 0.0113 ) . Most psychosocial outcomes improved , including global self-worth , but there were few dietary , physical activity , or sedentary behavior changes . No difference was found in primary outcomes between participants who did or did not receive additional therapeutic contact . CONCLUSIONS The Loozit r and omized controlled trial produced a significant but modest reduction in body mass index z score and improved psychosocial outcomes at 12 months . Supplementary telephone and electronic contact provided no additional benefit at 12 months . Trial Registration anzctr.org.au Identifier : 12606000175572 The prevalence of childhood overweight has increased significantly , with the highest rates noted among Mexican Americans . Many negative health outcomes are associated with overweight ; thus , there is a need for effective weight-loss interventions tailored to this group . This study evaluated 24-month outcomes of a r and omized , controlled trial involving an intensive lifestyle-based weight maintenance program targeting overweight Mexican-American children at a charter school in Houston , Texas . A total of 60 children ( 33 males , 55 % ) between the ages of 10 and 14 at or > 85th percentile for BMI were recruited . Participants were r and omized to an instructor-led intervention ( ILI ) or a self-help ( SH ) program , both aim ed at modifying eating and physical activity behaviors using behavior modification strategies . Changes in participants ' st and ardized BMI ( z BMI ) were assessed at baseline , 1 , and 2 years . Tricep skinfold , total cholesterol , triglycerides , high-density lipoprotein cholesterol , and calculated low-density lipoprotein were assessed at baseline and 1 year . ILI participants showed significantly greater decreases in z BMI at 1 and 2 years ( F = 26.8 , P < 0.001 , F = 4.1 , P < 0.05 , respectively ) compared to SH controls . ILI participants showed greater improvements in body composition , as measured by tricep skinfold ( F = 9.75 , P < 0.01 ) . Children in the ILI condition experienced benefits with respect to total cholesterol ( F = 7.19 , P < 0.05 ) and triglycerides ( F = 4.35 , P < 0.05 ) compared to children in the SH condition . Overall , the school-based intervention result ed in improved weight and clinical outcomes in overweight Mexican-American children , and z BMI was maintained over 2 years BACKGROUND Aerobic exercise improves cardiovascular health in general , but whether the impact varies with exercise intensity is not clear . OBJECTIVE The aim of the current study was to compare the effects of a high-intensity aerobic exercise training ( HIT ) vs. a low-intensity aerobic exercise training ( LIT ) on blood pressure ( BP ) , heart rate ( HR ) and heart rate variability ( HRV ) in obese adolescents . METHODS Forty-three ( 13 - 18 years ) Tanner stage ( III-IV ) matched obese adolescents were studied in a r and omized trial of either HIT ( corresponding to the ventilatory threshold I ; n = 20 ) or LIT ( corresponding to 20 % below the ventilatory threshold I ; n = 23 ) programme for a period of 6 months . All participants also received a multidisciplinary therapy that included nutritional , psychological and clinical counselling . Both HIT and LIT sessions were isocaloric , with energy expenditure set at 350 kcal . BP , HR and HRV were measured along with markers of body adiposity and insulin resistance before and after the respective interventions . RESULTS The participants in both groups had similar physical and clinical characteristics . After the 6-month intervention , systolic , diastolic and mean BP decreased ( P < 0.05 , for all ) similarly in both groups , whereas waist circumference , HR and HRV showed beneficial changes only in the HIT group ( P < 0.05 ) . CONCLUSION Aerobic exercise training set at a high intensity compared with the low intensity appears to have additional benefits on abdominal obesity and cardiovascular health in that it enhances the parasympathetic and autonomic modulation of the heart in obese adolescents Adolescents with obesity ( N = 48 ) and their caregivers were r and omized to Multisystemic Therapy ( MST ) or a group weight-loss intervention . MST adolescents significantly reduced percents overweight and body fat , while control adolescents did not . Treatments such as MST that can intervene in the multiple systems that influence weight are worthy of further study PURPOSE To pilot motivational interviewing ( MI ) targeting weight-related behaviors in African American adolescents with body mass index ≥85th percentile . METHODS A total of 44 adolescents were r and omly assigned to MI or nutrition counseling with baseline and 3-month assessment . RESULTS MI group reported improved eating behaviors and activity motivation . CONCLUSION Brief clinic-based MI interventions merit further study in this population This paper reports the final 24-month outcomes of a r and omized controlled trial evaluating the effect of additional therapeutic contact ( ATC ) as an adjunct to a community-based weight-management program for overweight and obese 13–16-year-olds . ATC involved telephone coaching or short-message-service and /or email communication once per fortnight . Adolescents were r and omized to receive the Loozit group program — a two-phase behavioral lifestyle intervention with ( n=73 ) , or without ( n=78 ) , ATC in Phase 2 . Adolescents/parents separately attended seven weekly group sessions ( Phase 1 ) , followed by quarterly adolescent sessions ( Phase 2 ) . Assessor-blinded , 24-month changes in anthropometry and metabolic health included primary outcomes body mass index ( BMI ) z-score and waist : height ratio ( WHtR ) . Secondary outcomes were self-reported psychosocial and lifestyle changes . By 24 months , 17 adolescents had formally withdrawn . Relative to the Loozit program alone , ATC largely had no impact on outcomes . Secondary pre-post assessment of the Loozit group program showed mean ( 95 % CI ) reductions in BMI z-score ( −0.13 ( −0.20 , −0.06 ) ) and WHtR ( −0.02 ( −0.03 , −0.01 ) ) in both arms , with several metabolic and psychosocial improvements . Adjunctive ATC did not provide further benefits to the Loozit group program . We recommend that further work is needed to optimize technological support for adolescents in weight-loss maintenance . Australian New Zeal and Clinical Trials Registry Number ACTRNO12606000175572 BACKGROUND & AIMS Few studies evaluating treatment of adolescent obesity have been published . Therefore , long-term effects of the Go4it group treatment for obese adolescents were examined . METHODS Obese adolescents ( 11 - 18 years ) visiting an outpatient paediatric obesity clinic were r and omly assigned to 1 ) intervention group ( Go4it ) or 2 ) current regular care i.e. referral to a dietician in the home care setting ( controls ) . Linear mixed models analysis was performed to evaluate intervention effects . Effect modification by sex , age and ethnicity was checked . Outcome measures included body mass index st and ard deviation score ( BMI sds ) , body composition and metabolic components at 6 and 18 months follow-up . RESULTS 122 adolescents , 71 Go4it and 51 controls , with a mean BMI sds of 2.9 ± 0.5 were r and omised . At 18 months a modest significant reduction in BMI sds ( between group difference : -0.16 ; 95%CI : -0.30 , -0.02 ; p = .028 ) was observed . None of the other body composition or metabolic components showed significant treatment effects . Ethnicity was a significant effect modifier . Posthoc analysis showed a large significant reduction on BMI sds ( between group difference : -0.35 ; 95%CI : -0.64 , -0.07 ) at 18 months for obese adolescents from western descent , while no effect was observed for adolescents from non-western descent . Significant treatment effects were also observed for systolic and diastolic blood pressure , as well as HDL cholesterol level , but only for obese adolescents from western descent . CONCLUSIONS Go4it showed promising long-term effects on BMI sds compared with regular care in obese adolescents . Larger benefits were achieved for adolescents of western ethnicity . This trial was registered at www.trialregister.nl with the Netherl and s Trial Register as IS RCT N27626398 |
2,239 | 20,946,476 | When learners were involved in choosing learning re sources , SDL was more effective .
Advanced learners seemed to benefit more from SDL .
CONCLUSIONS Moderate quality evidence suggests that SDL in health professions education is associated with moderate improvement in the knowledge domain compared with traditional teaching methods and may be as effective in the skills and attitudes domains | OBJECTIVES Given the continuous advances in the biomedical sciences , health care professionals need to develop the skills necessary for life-long learning .
Self-directed learning ( SDL ) is suggested as the methodology of choice in this context .
The purpose of this systematic review is to determine the effectiveness of SDL in improving learning outcomes in health professionals . | PURPOSE To evaluate the efficacy of the e-learning course " Genetics of Epilepsies " and to assess the experiences of the participants and e-moderators with this new approach . METHODS Prospect i ve , controlled study with waiting group ( control group , n = 18 ) and e-learning group ( n = 20 ) . The control group got the same reference literature list as the e-learning group . Both groups were assessed twice : The e-learning group before and after the course ; the control group was assessed at the same times . PRIMARY OUTCOME MEASURE increase in knowledge about genetics of epilepsies using question naires based on items formulated by experts ( internal consistency , Cronbach 's alpha = 0.86 ) . Main hypothesis : greater increase of knowledge in the e-learning group compared to control group . SECONDARY OUTCOME MEASURES assessment of the educational course and learning environment by participants and by tutors/e-moderators . RESULTS Significant time x group interaction and group effect ( ANOVA , each p < 0.01 ) with regard to knowledge . At baseline , the groups did not differ with respect to knowledge about genetics of epilepsy . In contrast to the control group , the increase of knowledge in the e-learning group was highly significant ( p < 0.001 ) . The majority of the participants of the e-learning course was content with their personal learning process ( 75 % agree , 15 % strongly agree ) . Most of them reported a gain in competence in the treatment and counseling of people with epilepsy ( 38.9 % agree , 50 % strongly agree ) . All participants would recommend this course to others and all but one participant are interested in other e-learning courses . CONCLUSION The study indicates e-learning courses are an appropriate tool to improve knowledge of physicians in genetics of epilepsy BACKGROUND We evaluated the impact of expert instruction during laboratory-based basic surgical skills training on subsequent performance of more complex surgical tasks . METHODS Forty-five junior residents were r and omized to learn basic surgical skills in either a self-directed or faculty-directed fashion . Residents returned to the laboratory 2 days later and were evaluated while performing 2 tasks : skin closure and bowel anastomosis . Outcome measures included Objective Structured Assessment of Technical Skill , time to completion , final product quality , and resident perceptions . RESULTS Objective Structured Assessment of Technical Skill , time to completion , and skin esthetic ratings were not better in the faculty-directed group , although isolated improvement in anastomotic leak pressure was seen . Residents perceived faculty-directed training to be superior . CONCLUSIONS Our data provided minimal objective evidence that faculty-directed training improved transfer of learned skills to more complex tasks . Residents perceived that there was a benefit of faculty mentoring . Curriculum factors related to training of basic skills and subsequent transfer to more complex tasks may explain these contrasting results STUDY OBJECTIVE We conducted a prospect i ve , r and omized , controlled trial to test the hypothesis that a 34-minute video self-instruction ( VSI ) training program for adult CPR would yield comparable or better CPR performance than the current community st and ard , the American Heart Association Heartsaver course . METHODS Incoming freshman medical students were r and omly assigned to VSI or the Heartsaver CPR course . Two to 6 months after training , we tested subjects to determine their ability to perform CPR in a simulated cardiac arrest setting . Blinded observers used explicit criteria to assess our primary outcome , CPR performance skill . In addition , we assessed secondary outcomes including sequential performance of individual skills , ventilation and chest compression characteristics , and written tests of CPR-related knowledge and attitudes . RESULTS VSI trainees displayed superior overall performance compared with traditional trainees . Twenty of 47 traditional trainees ( 43 % ) were judged not competent in their performance of CPR , compared with only 8 of 42 VSI trainees ( 19 % ; absolute difference , 24 % ; 95 % confidence interval , 5 % to 42 % ) . CONCLUSION In a group of incoming freshman medical students , we found that a half-hour of VSI result ed in superior overall CPR performance compared with that in traditional trainees . If vali date d by further research , VSI may provide a simple , quick , and inexpensive alternative to traditional CPR instruction for health care workers and , perhaps , the general population Background To evaluate the educational effects of a clinical ly integrated e-learning course for teaching basic evidence -based medicine ( EBM ) among postgraduates compared to a traditional lecture-based course of equivalent content . Methods We conducted a cluster r and omised controlled trial in the Netherl and s and the UK involving postgraduate trainees in six obstetrics and gynaecology departments . Outcomes ( knowledge gain and change in attitude towards EBM ) were compared between the clinical ly integrated e-learning course ( intervention ) and the traditional lecture based course ( control ) . We measured change from pre- to post-intervention scores using a vali date d question naire assessing knowledge ( primary outcome ) and attitudes ( secondary outcome ) . Results There were six clusters involving teaching of 61 postgraduate trainees ( 28 in the intervention and 33 in the control group ) . The intervention group achieved slightly higher scores for knowledge gain compared to the control , but these results were not statistically significant ( difference in knowledge gain : 3.5 points , 95 % CI -2.7 to 9.8 , p = 0.27 ) . The attitudinal changes were similar for both groups . Conclusion A clinical ly integrated e-learning course was at least as effective as a traditional lecture based course and was well accepted . Being less costly than traditional teaching and allowing for more independent learning through material s that can be easily up date d , there is a place for incorporating e-learning into postgraduate EBM curricula that offer on-the-job training for just-in-time learning . Trial registration Trial registration number : ACTRN12609000022268 This study was design ed to assess whether a self- study interactive computer program is more effective than weekly seminars for teaching fundamental skills of electrocardiographic interpretation to junior medical students . Forty-two students were assigned to the computer and 41 to the seminar group . A test was given to each participant at the beginning and end of each rotation . The computer group used a computer-assisted learning program , and the seminar group met weekly with a cardiologist to review electrocardiograms . Attendance at a minimum of 80 % of the seminars or completion of 80 % of the computer-assisted learning program was required for inclusion in the statistical analysis . The mean difference in test scores before and after study was 5.69 for the computer group and 4.36 for the seminar group ( P less than .02 by one-tailed t-test ) . These results indicate that the computer group performed significantly better than the seminar group . We believe this difference to be educationally important A growing body of literature deals with the use of self-instructional methods for teaching biostatistics to medical students . The University of Tennessee Department of Community Medicine tested the hypothesis that , in controlled , r and omized situations , learning of statistical material by self-instruction is equivalent to learning identical material by the lecture method . An analysis of student performance , in terms of the grade s obtained on two separate examinations , showed that students learning by self-instruction did as well or better than their colleagues taking lectures . On the basis of these results , self-instructional biostatistics for medical students at the University of Tennessee has been selected as the major teaching method of that subject BACKGROUND Although educators agree that the approach to cancer management must be multidisciplinary , medical students usually observe cancer patients through the eyes of a single specialist at any given time . METHODS In order to teach third-year medical students that cancer management is multidisciplinary , we developed the Oncology Game , an interactive , computer-assisted board game built on the principles of self-directed learning and student-student interaction . Eight " patients " with different histologic types of cancer are distributed r and omly to 4 students , who play in teams of 2 . The object is for the team to obtain the best treatment for its patients by advancing them via a roll of dice through surgical , medical , and radiation oncology clinics in the order most logical for the patient 's particular cancer type . To test improvement in cognitive skills as a function of play , 16 students participated in a tournament taking parallel pretest and posttests before and after each round of play . RESULTS Students demonstrated a statistically significant change in the total number of questions answered correctly each time they played the Oncology Game ( F = 4.16 , P = 0.018 ; Pretest Round 1 : 8.88 + /- 0.58 ; Posttest Round 1 : 9.63 + /- 0.42 ; Pretest Round 2 : 10.75 + /- 0.62 ; Posttest Round 2 : 11.5 + /- 0.85 ) . Post hoc pairwise comparison revealed a significant improvement in student performance after playing two rounds of the Oncology Game . Based on the postgame survey , students felt they improved their underst and ing of oncologic principles ( 4.56 + /- 0.13 ) , knowledge of malignancies ( 4.50 + /- 0.13 ) , and appreciation for the multidisciplinary nature of cancer management ( 4.56 + /- 0.13 ) . CONCLUSIONS Improved test scores and postgame survey results demonstrate that third-year medical student students can learn about basic oncology principles and gain an appreciation for oncology as a multidisciplinary field of medicine through an interactive , computer-assisted board game BACKGROUND Procedural sedation guidelines were established for a tertiary care pediatric emergency department ( ED ) . We developed a pediatric procedural sedation course to disseminate these guidelines . OBJECTIVE Our objective was to evaluate the effectiveness of a sedation course in improving physicians ' knowledge of pediatric procedural sedation practice s and guidelines , relative to individual self-directed learning . METHODS We recruited emergency staff physicians and fellows as well as fourth-year pediatric residents in a tertiary care pediatric ED to participate in a r and omized , controlled , educational intervention . All consenting physicians received pediatric sedation educational material for individual study 2 weeks before a learning assessment . Participants were r and omly assigned to one of 2 groups . The self-directed learning group ( n = 24 ) completed a multiple-choice examination without receiving any formal teaching . The study group ( n= 24 ) participated in a 4-hour formal multifaceted sedation course before writing the multiple-choice examination . RESULTS The groups did not differ significantly in demographic characteristics or self-perceived knowledge of pediatric sedation . The formal teaching group 's median examination score ( 83.3 % ; range 75.8%-96.5 % ) was significantly higher ( p < 0.0001 ) than the median examination score of participants in the self-directed study group ( 73.3 % , range 43.5%-86.6 % ) . CONCLUSION The multifaceted sedation course was more effective in improving physician knowledge and underst and ing of sedation guidelines and practice s than unstructured , self-directed learning A study was undertaken to test the hypothesis that self-instructional programs in nutrition and dentistry are as effective a teaching method as traditional lectures . Five programmed self-instructional manuals accompanied by 191 slides were developed and evaluated for effectiveness , as compared to six lectures containing the same information . The study population of 83 freshmen dental students was r and omly assigned to a control ( lecture ) group and an experimental ( self-instruction ) group . Cognitive tests , performance criteria for diet counseling , and an attitudinal question naire were used to compare the two groups . The results of the analysis demonstrated that there was no significant difference in the test scores in the lecture and self-instruction groups A computer-assisted interactive videodisc instructional program , HP-RHEUM was design ed to teach clinical findings in arthritis to occupational and physical therapy students . Using the Rheumatology Image Library videodisc produced by the National Library of Medicine , HP-RHEUM consists of instructional modules which employ advance organizers , examples/nonexamples , summaries , and immediate feedback . To see if HP-RHEUM would be as effective as traditional classroom instruction , control data were collected in 1991 from 52 OT and PT students . Treatment data were collected from 61 students in 1992 when HP-RHEUM entirely replaced lectures . Identical pre- and post-tests consisted of 70 multiple choice questions , with 24 matched to slides . On the slide questions the HP-RHEUM group had significantly higher scores . Otherwise , there was no significant difference in performance between groups . HP-RHEUM provided an independent learning method and enhanced visual comprehension of rheumatologic disease concepts OBJECTIVES The GMC recommends that students become independent learners , while tutor time is an increasingly precious re source . A set of structured learning material s requiring students to undertake and reflect on practical tasks in five learning areas was developed . DESIGN The study used a r and omized control trial to evaluate the effectiveness of using these structured learning material s in place of conventional teaching for 228 third-year undergraduate students and 55 teachers , on both hospital and community based medical and general practice firms . Evaluation involved assessing student performance on an examination question and a writing task , together with a student and tutor satisfaction question naire . SETTING King 's College School of Medicine and Dentistry , London . SUBJECTS Third-year medical ( first-year clinical ) undergraduates . RESULTS No significant difference in learning outcome was found for students on community- and hospital-based medical and general practice firms between students who had used the structured material s and those who had had conventional teaching on the same topic . The packs were acceptable to tutors and students . CONCLUSIONS Such re sources represent a mid-point between formal didactic teaching and self-directed learning . They may be particularly suitable for promoting independent learning for students on traditional medical courses . They offer an appropriate way to cover certain topics in the clinical curriculum and help to protect tutor time for topics which can not be effectively taught in other ways This study evaluated 2 methods of disseminating an empirically vali date d smokeless tobacco intervention delivered during routine dental care . Twenty cities within 12 states were stratified and then r and omized to 1 of 3 groups : personalized instruction ( PI ) , self- study ( SS ) , or delayed training ( DT ) control . Dental hygienists in the SS condition were sent a manual and video . Those in the PI condition were recruited to attend a workshop . Thirty-seven percent of eligible hygienists agreed to participate . At 12 months postenrollment , hygienists in the SS and PI conditions significantly increased their " Assist " behaviors ( discuss cessation techniques , help patient set a quit date , and provide cessation material s ) and reported fewer perceived barriers to delivering the intervention as compared with hygienists in DT . An economic analysis suggests that SS is more cost-effective than PI BACKGROUND Exposure therapy is effective for phobic anxiety disorders ( specific phobias , agoraphobia , social phobia ) and panic disorder . Despite their high prevalence in the community , sufferers often get no treatment or if they do , it is usually after a long delay . This is largely due to the scarcity of healthcare professionals trained in exposure therapy , which is due , in part , to the high cost of training . Traditional teaching methods employed are labour intensive , being based mainly on role-play in small groups with feedback and coaching from experienced trainers . In an attempt to increase knowledge and skills in exposure therapy , there is now some interest in providing relevant teaching as part of pre- registration nurse education . Computers have been developed to teach terminology and simulate clinical scenarios for health professionals , and offer a potentially cost effective alternative to traditional teaching methods . OBJECTIVE To test whether student nurses would learn about exposure therapy for phobia/panic as well by computer-aided self-instruction as by face-to-face teaching , and to compare the individual and combined effects of two educational methods , traditional face-to-face teaching comprising a presentation with discussion and questions /answers by a specialist cognitive behaviour nurse therapist , and a computer-aided self-instructional programme based on a self-help programme for patients with phobia/panic called FearFighter , on students ' knowledge , skills and satisfaction . DESIGN R and omised controlled trial , with a crossover , completed in 2 consecutive days over a period of 4h per day . PARTICIPANTS Ninety-two mental health pre- registration nursing students , of mixed gender , age and ethnic origin , with no previous training in cognitive behaviour therapy study ing at one UK university . RESULTS The two teaching methods led to similar improvements in knowledge and skills , and to similar satisfaction , when used alone . Using them in t and em conferred no added benefit . Computer-aided self-instruction was more efficient as it saved teacher preparation and delivery time , and needed no specialist tutor . CONCLUSION Computer-aided self-instruction saved almost all preparation time and delivery effort for the expert teacher . When added to past results in medical students , the present results in nurses justify the use of computer-aided self-instruction for learning about exposure therapy and phobia/panic and of research into its value for other areas of health education Background : Because practice -based learning and improvement ( PBLI ) is a core competency for residents , the fundamentals of PBLI should be developed in medical school . Purpose : Evaluate the effects of a PBLI module for 1st-year students at Dartmouth Medical School in 2004–05 . Methods : Design . R and omized two-group trial ( early and late intervention ) . Intervention . One half of students received the st and ard curriculum— review ing student – patient – preceptor reports with their small-group facilitator and student colleagues . The other half received the PBLI-DMEDS module— review ing student – patient-preceptor reports and applying PBLI methods to history and physical exam skills . Analysis . The module was assessed on ( a ) core learning of PBLI ( pre- and postmodule ) ; ( b ) student self-assessed proficiency in PBLI ( pre- and postmodule ) ; ( c ) student , faculty , and course leaders ' satisfaction ; and ( d ) time costs . Results : Pretest PBLI knowledge scores were similar in both groups ; intervention students scored significantly higher after the PBLI-DMEDS module . Satisfaction of students , faculty , and course leaders was mixed . The time cost required to implement the module was excessive . Conclusions : The intervention effectively taught the basics of PBLI but did not integrate well into the core curriculum . Our multifaceted evaluation approach allowed us to amplify aspects of the intervention that worked well and discard those that did not OBJECTIVES To compare 2 educational programmes for teaching evidence -based medicine ( EBM ) . DESIGN Prospect i ve r and omised controlled trial accompanied by a qualitative evaluation . SETTING University of Oslo , Norway , 2002 - 03 . PARTICIPANTS A total of 175 students entered the study . All tenth semester medical students from 3 semesters were eligible for inclusion if they completed baseline assessment and consent forms and either attended teaching on the first day of the semester or gave reasons for their absence on the first day in advance . Interventions One intervention was based on computer-assisted , self-directed learning ( self-directed intervention ) , whilst the other was organised as workshops based on social learning theory ( directed intervention ) . Both educational interventions consisted of 5 half-day sessions . MAIN OUTCOME MEASURES The primary outcomes were knowledge about EBM and skills in critical appraisal . A secondary outcome measured attitudes to EBM . Outcomes were compared on an intention-to-treat basis using a stratified Wilcoxon rank-sum test . RESULTS There were no differences in outcomes for the 2 study groups in terms of EBM knowledge ( mean deviation 0.0 [ 95 % confidence interval - 1.0 , 1.0 ] , P = 0.8 ) , critical appraisal skills ( MD 0.1 [ 95 % CI - 0.9 , 1.1 ] , P = 0.5 ) , or attitudes to EBM ( MD - 0.3 [ 95 % CI - 1.4 , 0.8 ] , P = 0.5 ) . Follow-up rates were 96 % , 97 % and 63 % , respectively . CONCLUSIONS This trial and its accompanying qualitative evaluation suggest that self-directed , computer-assisted learning may be an alternative format for teaching EBM . However , further research is needed to confirm this and investigate alternative educational models OBJECTIVES We have developed both a computer-assisted instruction ( CAI ) multimedia program and a textbook on arterial blood gas interpretation with the same content as formal didactic instruction . A prospect i ve , r and omized study was design ed to compare the outcomes of self-learning using the software and using the textbook . METHODS 80 third-year medical students were r and omly allocated to two groups : the CAI ( n=40 ) and text group ( n=40 ) . A 30-item , type-K examination was administered as the pre-test . After the pre-test , the volunteers in the CAI group studied the software program , whereas those in the text group spent their time reading the textbook covering the same material . The post-test was held immediately at the end of a full day of study , and 3 weeks later , the final test was performed without prior notice . A P value of < 0.05 was considered to be a statistically significant difference . RESULTS Students in the text group seemed to fulfil their assignments and improved their scores post-test better than those in the CAI group . After 3 weeks , the final test scores of both groups demonstrated a significant decrease , but showed an insignificant difference between the two groups . CONCLUSION Text-based learning seems to be a convenient method of education where time is limited . However , with more time available , use of software may be as good as the conventional learning method and can be an alternative tool . The computer-assisted instruction program seems to enhance the learning process |
2,240 | 24,853,307 | Depression-screening instruments yielded relatively high false positive rates .
Overall , few studies described the reliability and /or validity of depression instruments in sub-Saharan Africa | OBJECTIVE The aim of this study was to systematic ally review the reliability and validity of instruments used to screen for major depressive disorder or assess depression symptom severity among persons with HIV in sub-Saharan Africa . | OBJECTIVES We assessed whether directly observed fluoxetine treatment reduced depression symptom severity and improved HIV outcomes among homeless and marginally housed HIV-positive adults in San Francisco , California , from 2002 to 2008 . METHODS We conducted a nonblinded , r and omized controlled trial of once-weekly fluoxetine , directly observed for 24 weeks , then self-administered for 12 weeks ( n = 137 persons with major or minor depressive disorder or dysthymia ) . Hamilton Depression Rating Scale score was the primary outcome . Response was a 50 % reduction from baseline and remission a score below 8 . Secondary measures were Beck Depression Inventory-II ( BDI-II ) score , antiretroviral uptake , antiretroviral adherence ( measured by unannounced pill count ) , and HIV-1 RNA viral suppression ( < 50 copies/mL ) . RESULTS The intervention reduced depression symptom severity ( b = -1.97 ; 95 % confidence interval [ CI ] = -0.85 , -3.08 ; P < .001 ) and increased response ( adjusted odds ratio [ AOR ] = 2.40 ; 95 % CI = 1.86 , 3.10 ; P < .001 ) and remission ( AOR = 2.97 ; 95 % CI = 1.29 , 3.87 ; P < .001 ) . BDI-II results were similar . We observed no statistically significant differences in secondary HIV outcomes . CONCLUSIONS Directly observed fluoxetine may be an effective depression treatment strategy for HIV-positive homeless and marginally housed adults , a vulnerable population with multiple barriers to adherence Spiritual models of illness causation are common in Africa . This article reports an investigation of some clinical correlates of patients who believe that their problem has a spiritual cause . A cross‐sectional survey of r and om attenders at primary health care clinics and traditional medical practitioners ( TMP ) in Harare ( n= 302 ) was performed . Interviews included eliciting of explanatory models , indigenous and etic psychiatric measures . Spiritual models of illness were held by half the subjects . Patients who hold this model had higher levels of mental disorder and were more likely to have a mental illness as judged by the patient , care provider and psychiatric measures . The symptoms of such patients resemble the construct of anxiety . Such patients are more likely to consult TMP and to have a chronic illness . Spiritual models of illness may represent an indigenous model to explain the distressing symptoms of nonpsychotic mental illness . Including them in training of primary health care providers may improve the recognition of mental illness CONTEXT Depression strongly predicts nonadherence to human immunodeficiency virus ( HIV ) antiretroviral therapy , and adherence is essential to maintaining viral suppression . This suggests that pharmacologic treatment of depression may improve virologic outcomes . However , previous longitudinal observational analyses have inadequately adjusted for time-varying confounding by depression severity , which could yield biased estimates of treatment effect . Application of marginal structural modeling to longitudinal observation data can , under certain assumptions , approximate the findings of a r and omized controlled trial . OBJECTIVE To determine whether antidepressant medication treatment increases the probability of HIV viral suppression . DESIGN Community-based prospect i ve cohort study with assessment s conducted every 3 months . SETTING Community-based research field site in San Francisco , California . PARTICIPANTS One hundred fifty-eight homeless and marginally housed persons with HIV who met baseline immunologic ( CD4 + T-lymphocyte count , < 350/μL ) and psychiatric ( Beck Depression Inventory II score , > 13 ) inclusion criteria , observed from April 2002 through August 2007 . MAIN OUTCOME MEASURES Probability of achieving viral suppression to less than 50 copies/mL. Secondary outcomes of interest were probability of being on an antiretroviral therapy regimen , 7-day self-reported percentage adherence to antiretroviral therapy , and probability of reporting complete ( 100 % ) adherence . RESULTS Marginal structural models estimated a 2.03 greater odds of achieving viral suppression ( 95 % confidence interval [ CI ] , 1.15 - 3.58 ; P = .02 ) result ing from antidepressant medication treatment . In addition , antidepressant medication use increased the probability of antiretroviral uptake ( weighted odds ratio , 3.87 ; 95 % CI , 1.98 - 7.58 ; P < .001 ) . Self-reported adherence to antiretroviral therapy increased by 25 percentage points ( 95 % CI , 14 - 36 ; P < .001 ) , and the odds of reporting complete adherence nearly doubled ( weighted odds ratio , 1.94 ; 95 % CI , 1.20 - 3.13 ; P = .006 ) . CONCLUSIONS Antidepressant medication treatment increases viral suppression among persons with HIV . This effect is likely attributable to improved adherence to a continuum of HIV care , including increased uptake and adherence to antiretroviral therapy Background This study was conducted to evaluate the diagnostic accuracy and determine the optimum cut-off scores for clinical use of the Center for Epidemiological Studies Depression scale ( CES-D ) and Alcohol Use Disorders Identification Test ( AUDIT ) against a reference psychiatric diagnostic interview , in TB and anti-retroviral therapy ( ART ) patients in primary care in Zambia . Methods This was a cross-sectional study in 16 primary level care clinics . Consecutive sampling was used to select 649 participants who started TB treatment or ART in the preceding month . Participants were first interviewed using the CES-D and AUDIT , and subsequently with a psychiatric diagnostic interview for current major depressive disorder ( MDD ) and alcohol use disorders ( AUDs ) using the Mini-International Neuropsychiatric Interview ( MINI ) . The diagnostic accuracy was calculated using the Area Under the Receiver Operating Characteristic curve ( AUROC ) . The optimum cut-off scores for clinical use were calculated using sensitivity and positive predictive value ( PPV ) . Results The CES-D and AUDIT had high internal consistency ( Cronbach 's alpha = 0.84 ; 0.98 respectively ) . Confirmatory factor analysis showed that the four-factor CES-D model was not a good fit for the data ( Tucker-Lewis Fit Index ( TLI ) = 0.86 ; st and ardized root-mean square residual ( SRMR ) = 0.06 ) while the two-factor AUDIT model fitted the data well ( TFI = 0.99 ; SRMR = 0.04 ) . Both the CES-D and AUDIT demonstrated good discriminatory ability in detecting MINI-defined current MDDs and AUDs ( AUROC for CES-D = 0.78 ; AUDIT = 0.98 for women and 0.75 for men ) . The optimum CES-D cut-off score in screening for current MDD was 22 ( sensitivity 73 % , PPV 76 % ) while that of the AUDIT in screening for AUD was 24 for women ( sensitivity 60 % , PPV 60 % ) , and 20 for men ( sensitivity 55 % , PPV 50 % ) . Conclusions The CES-D and AUDIT showed high discriminatory ability in measuring MINI-defined current MDD and AUD respectively . They are suitable mental health screening tools for use among TB and ART patients in primary care in Zambia OBJECTIVE To assess the feasibility of using community health workers to administer short or ultra-short screening instruments during routine community-based prenatal outreach for detecting probable depression at 12 weeks postpartum . METHODS During pregnancy and at 12 weeks postpartum , the 10-item Edinburgh Postnatal Depression Scale ( EPDS-10 ) was administered to 249 Xhosa-speaking black African women living in Khayelitsha , South Africa . We compared the operating characteristics of the prenatal EPDS-10 , as well as 4 short and ultra-short subscales , with the criterion st and ard of probable postpartum depression . RESULTS Seventy-nine ( 31.7 % ) women were assessed as having probable postpartum depression . A prenatal EPDS-10 score of 13 or higher had 0.67 sensitivity and 0.67 specificity for detecting probable postpartum depression . Briefer subscales performed similarly . CONCLUSION Community health workers successfully conducted community-based screening for depression in a re source -limited setting using short or ultra-short screening instruments . However , overall feasibility was limited because prenatal screening failed to accurately predict probable depression during the postpartum period The authors ’ objective was to estimate the prevalence of major depressive disorder among Rw and ans 5 years after the 1994 genocidal civil war . They interviewed a community-based r and om sample of adults in a rural part of Rw and a using the Hopkins Symptom Checklist and a locally developed functional impairment instrument . The authors estimated current rates of major depression using an algorithm based on the DSM-IV symptom criteria ( A ) , distress/functional impairment criteria ( C ) , and bereavement exclusionary criteria ( E ) . They also examined the degree to which depressive symptoms compromise social and occupational functioning . Three hundred sixty-eight adults were interviewed , of whom 15.5 % met Criteria A , C , and E for current major depression . Depressive symptoms were strongly associated with functional impairment in most major roles for men and women . The authors conclude that a significant part of this population has seriously disabling depression . Work on appropriate , feasible , safe , and effective mental health interventions should be a priority for this population Depressed mood has been associated with HIV transmission risk behavior . To determine whether effective depression treatment could reduce the frequency of sexual risk behavior , we analyzed secondary outcome data from a 36-week , two-arm , parallel- design , r and omized controlled trial , in which homeless and marginally housed , HIV-infected persons with comorbid depressive disorders were r and omized to receive either : ( a ) directly observed treatment with the antidepressant medication fluoxetine , or ( b ) referral to a local public mental health clinic . Self-reported sexual risk outcomes , which were measured at 3 , 6 , and 9 months , included : total number of sexual partners , unprotected sexual intercourse , unprotected sexual intercourse with an HIV-uninfected partner or a partner of unknown serostatus , and transactional sex . Estimates from generalized estimating equations regression models did not suggest consistent reductions in sexual risk behaviors result ing from treatment . Mental health interventions may need to combine depression treatment with specific skills training in order to achieve durable impacts on HIV prevention outcomes The purpose of this study is to evaluate empirical criticism of the psychometric properties of the Hamilton Depression Rating Scale ( HDRS ) by undertaking an " internal construct validity " evaluation . Individual symptom responses for the HDRS were obtained from 370 patients meeting Research Diagnostic Criteria for major depression . A multidimensional normal item response theory ( IRT ) model was used to assess the dimensionality of the HDRS and estimate corresponding item parameters which were then expressed as factor loadings and item thresholds . The analysis yielded a five-dimensional solution . The first dimension ( depressed mood , guilt , suicide , work and interests , agitation , psychic anxiety , somatic anxiety , and loss of libido ) appeared to define global depression severity . These results are consistent with other published factor analytic studies and provide further justification for thinking that the HDRS total score is a weak index of depressive syndrome severity . The findings provide a benchmark by which the adequacy of future results may be judged , because the multidimensional IRT model does not suffer from the statistical limitations that arise when applying traditional factor analytic methods to discrete symptom ratings The objective of this study was to develop an indigenous measure of common mental disorders ( CMD ) in the Shona language in Zimbabwe . Ethnographic and qualitative studies elicited idioms of distress of mental disorder leading to the preliminary Shona Symptom Question naire ( SSQ ) , and items from the Self‐Report Question naire ( SRQ ) were added to it . The 56‐item Preliminary Shona Symptom Question naire ( PSSQ ) was administered to 302 r and omly selected primary care attenders , of whom 100 were classified as cases on the basis of agreement between care provider assessment and a psychiatric interview . Discriminant analysis identified 14 items that were the strongest predictors of mental disorder . The 14‐item SSQ has a high level of internal consistency ( Cronbach 's alpha=0.85 ) . The items are a mixture of emic and etic phenomena . The total score correlates strongly with patients ' self‐ assessment of the emotional nature of their illness . Satisfactory specificity and sensitivity occurred at a cut‐off point of 7/8 . The SSQ is the first indigenous measure of mental disorder developed in sub‐Saharan Africa to have included idioms of distress of primary care attenders and involved patients consulting traditional medical practitioners . It promises to be a useful instrument for epidemiological and clinical research . The methodology used is an innovative way of combining etic and emic methods in the evaluation of CMD Objective : To determine whether earlier initiation of antiretroviral therapy ( ART ) is associated with better economic outcomes . Design : Prospect i ve cohort study of HIV-positive patients on ART in rural Ug and a. Methods : Patients initiating ART at a regional referral clinic in Ug and a were enrolled in the Ug and a AIDS Rural Treatment Outcomes study starting in 2005 . Data on labor force participation and asset ownership were collected on a yearly basis , and CD4 + cell counts were collected at pre-ART baseline . We fitted multivariable regression models to assess whether economic outcomes at baseline and in the 6 years following ART initiation varied by baseline CD4 + cell count . Results : Five hundred and five individuals , followed up to 6 years , formed the estimation sample . Participants initiating ART at CD4 + cell count at least 200 cells/&mgr;l were 13 percentage points more likely to be working at baseline ( P < 0.01 , 95 % confidence interval 0.06–0.21 ) than those initiating below this threshold . Those in the latter group achieved similar labor force participation rates within 1 year of initiating ART ( P < 0.01 on the time indicators ) . Both groups had similar asset scores at baseline and demonstrated similar increases in asset scores over the 6 years of follow-up . Conclusion : ART helps participants initiating therapy at CD4 + cell count below 200 cells/&mgr;l rejoin the labor force , though the findings for participants initiating with higher CD4 + cell counts suggests that pretreatment declines in labor supply may be prevented altogether with earlier therapy . Baseline similarities in asset scores for those with early and advanced disease suggest that mechanisms other than morbidity may help drive the relationship between HIV infection and economic outcomes HIV/AIDS and food insecurity are two of the leading causes of morbidity and mortality in sub-Saharan Africa , with each heightening the vulnerability to , and worsening the severity of , the other . Less research has focused on the social determinants of food insecurity in re source -limited setting s , including social support and HIV-related stigma . In this study , we analyzed data from a cohort of 456 persons from the Ug and a AIDS Rural Treatment Outcomes study , an ongoing prospect i ve cohort of persons living with HIV/AIDS ( PLWHA ) initiating HIV antiretroviral therapy in Mbarara , Ug and a. Quarterly data were collected by structured interviews . The primary outcome , food insecurity , was measured with the Household Food Insecurity Access Scale . Key covariates of interest included social support , internalized HIV-related stigma , HIV-related enacted stigma , and disclosure of HIV serostatus . Severe food insecurity was highly prevalent overall ( 38 % ) and more prevalent among women than among men . Social support , HIV disclosure , and internalized HIV-related stigma were associated with food insecurity ; these associations persisted after adjusting for household wealth , employment status , and other previously identified correlates of food insecurity . The adverse effects of internalized stigma persisted in a lagged specification , and the beneficial effect of social support further persisted after the inclusion of fixed effects . International organizations have increasingly advocated for addressing food insecurity as part of HIV/AIDS programming to improve morbidity and mortality . This study provides quantitative evidence on social determinants of food insecurity among PLWHA in re source -limited setting s and suggests points of intervention . These findings also indicate that structural interventions to improve social support and /or decrease HIV-related stigma may also improve the food security of PLWHA CONTEXT The impact of depression on morbidity and mortality among women with human immunodeficiency virus ( HIV ) has not been examined despite the fact that women with HIV have substantially higher rates of depression than their male counterparts . OBJECTIVE To determine the association of depressive symptoms with HIV-related mortality and decline in CD4 lymphocyte counts among women with HIV . DESIGN The HIV Epidemiologic Research Study , a prospect i ve , longitudinal cohort study conducted from April 1993 through January 1995 , with follow-up through March 2000 . SETTING Four academic medical centers in Baltimore , Md ; Bronx , NY ; Providence , RI ; and Detroit , Mich. PARTICIPANTS A total of 765 HIV-seropositive women aged 16 to 55 years . MAIN OUTCOME MEASURES HIV-related mortality and CD4 cell count slope decline over a maximum of 7 years , compared among women with limited or no depressive symptoms , intermittent depressive symptoms , or chronic depressive symptoms , as measured using the self-report Center for Epidemiologic Studies Depression Scale . RESULTS In multivariate analyses controlling for clinical , treatment , and other factors , women with chronic depressive symptoms were 2 times more likely to die than women with limited or no depressive symptoms ( relative risk [ RR ] , 2.0 ; 95 % confidence interval [ CI ] , 1.0 - 3.8 ) . Among women with CD4 cell counts of less than 200 x 10(6)/L , HIV-related mortality rates were 54 % for those with chronic depressive symptoms ( RR , 4.3 ; 95 % CI , 1.6 - 11.6 ) and 48 % for those with intermittent depressive symptoms ( RR , 3.5 ; 95 % CI , 1.1 - 10.5 ) compared with 21 % for those with limited or no depressive symptoms . Chronic depressive symptoms were also associated with significantly greater decline in CD4 cell counts after controlling for other variables in the model , especially among women with baseline CD4 cell counts of less than 500 x 10(6)/L and baseline viral load greater than 10 000 copies/microL. CONCLUSIONS Our results indicate that depressive symptoms among women with HIV are associated with HIV disease progression , controlling for clinical , substance use , and sociodemographic characteristics . These results highlight the importance of adequate diagnosis and treatment of depression among women with HIV . Further research is needed to determine if treatment of depression can not only enhance the mental health of women with HIV but also impede disease progression and mortality BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects DESCRIPTION After HIV diagnosis , timely entry into HIV medical care and retention in that care are essential to the provision of effective antiretroviral therapy ( ART ) . Adherence to ART is among the key determinants of successful HIV treatment outcome and is essential to minimize the emergence of drug resistance . The International Association of Physicians in AIDS Care convened a panel to develop evidence -based recommendations to optimize entry into and retention in care and ART adherence for people with HIV . METHODS A systematic literature search was conducted to produce an evidence base restricted to r and omized , controlled trials and observational studies with comparators that had at least 1 measured biological or behavioral end point . A total of 325 studies met the criteria . Two review ers independently extracted and coded data from each study using a st and ardized data extraction form . Panel members drafted recommendations based on the body of evidence for each method or intervention and then grade d the overall quality of the body of evidence and the strength for each recommendation . RECOMMENDATIONS Recommendations are provided for monitoring entry into and retention in care , interventions to improve entry and retention , and monitoring of and interventions to improve ART adherence . Recommendations cover ART strategies , adherence tools , education and counseling , and health system and service delivery interventions . In addition , they cover specific issues pertaining to pregnant women , incarcerated individuals , homeless and marginally housed individuals , and children and adolescents , as well as substance use and mental health disorders . Recommendations for future research in all areas are also provided Background : Major depressive disorder is highly prevalent among HIV-infected persons , and depression symptom severity improves during the course of HIV antiretroviral therapy ( ART ) . The potential biologic pathways explaining these phenomena remain unclear . We investigated the extent to which ART-mediated suppression of the kynurenine pathway of tryptophan catabolism ( via indoleamine 2,3-dioxygenase-1 and potentially other sources ) may correlate with improvements in depression symptom severity in this setting . Method : We used the first year of data from the Ug and a AIDS Rural Treatment Outcomes Study , a prospect i ve cohort of 504 HIV-infected individuals initiating their first ART regimen in rural Ug and a. We fitted r and om-effects regression models to estimate the associations between plasma tryptophan , plasma kynurenine , dietary diversity , and self-reported depression symptom severity . Results : Greater depressive symptoms were associated with both lower plasma tryptophan and higher plasma kynurenine/tryptophan ( KT ) ratio over 12-month follow-up . In multivariable-adjusted models , declines in KT ratio and increases in plasma tryptophan levels partially explained ART-mediated improvements in depressive symptom severity . The association between KT ratio and depression symptom severity was stronger among persons with protein-deficient diets than among those with protein-rich diets . Conclusions : Indoleamine 2,3-dioxygenase-1-mediated tryptophan catabolism may contribute to depression symptom severity among HIV-infected individuals , particularly among those with poor dietary protein intake . ART-mediated improvements in depressive symptom severity may also be at least partially mediated by immunologic mechanisms . Interventions to reduce immune activation , and dietary protein supplementation , may be promising strategies to further reduce depression in this setting Abstract . Background : We sought to assess the prevalence of major depression in a region of sub-Saharan Africa severely affected by HIV , using symptom and functional criteria as measured with locally vali date d instruments . Method : Six hundred homes in the Masaka and Rakai districts of southwest Ug and a were selected by weighted systematic r and om sampling . A locally vali date d version of the depression section of the Hopkins Symptom Check List ( DHSCL ) and a community-generated index of functional impairment were used to interview 587 respondents . Results : Of respondents,21 % were diagnosed with depression using three of the five DSM-IV criteria ( including function impairment ) compared with 24.4 % using symptom criteria alone . Increased age and lower educational levels are associated with a greater risk for depression ; however , a gender effect was not detected . Conclusions : Most community-based assessment s of depression in sub-Saharan Africa based on the DSM-IV have used symptom criteria only . We found that exp and ing criteria to more closely match the complete DSM-IV is feasible , thereby making more accurate assessment s of prevalence possible . This approach suggests that major depression and associated functional impairment are a substantial problem in this population OBJECTIVE To investigate whether high levels of depressive symptomatology at baseline predict more rapid decline of CD4 lymphocyte counts and progression of clinical disease in persons infected with the human immunodeficiency virus ( HIV ) . DESIGN Prospect i ve cohort study with semiannual data collection waves and up to 66 months of follow-up . SETTING Population -based probability sample of single men in areas of San Francisco with high case rates of the acquired immunodeficiency syndrome ( AIDS ) . SUBJECTS All 330 homosexual or bisexual men who by January 1985 had serological evidence of HIV infection but had not had an AIDS diagnosis . Analysis of CD4 lymphocyte change was performed for 277 subjects ( 83.9 % ) who had three or more CD4 lymphocyte counts recorded during the study period January 1985 through July 1990 . OUTCOME MEASURES Depressive symptoms were assessed using the Center for Epidemiologic Studies -Depression scale ( CES-D ) . All subjects were classified according to two indicators of depression : ( 1 ) as overall depressed using a cut point of 16 or higher on the complete CES-D , and ( 2 ) as affectively depressed using a cut point of more than 1 SD above the mean on a subscale of the CES-D measuring affective depression . Laboratory and symptom measures , antiretroviral use , demographics , and behavioral measures were also used . The primary outcome measure was the rate of change of the CD4 lymphocyte count . Secondary outcomes were AIDS-free survival and mortality . RESULTS At baseline 65 subjects ( 19.7 % ) were classified as depressed on the overall scale and 53 ( 16.1 % ) were classified as depressed on the affective scale . The unadjusted mean rate of CD4 change was 38 % greater for overall depressed subjects than for the overall nondepressed ( -0.0812 vs -0.0588 x 10(9)/L [ -81.2 vs -58.8/microL per year ; P = .07 ) and 34 % greater for affectively depressed subjects than for the affectively nondepressed ( -0.0804 vs -0.0598 x 10(9)/L per year ; P = .06 ) . In hierarchical multivariate analysis controlling for antiretroviral use , symptoms , and other predictors , baseline overall depression was associated with an excess decline in CD4 count of -0.0285 x 10(9)/L per year ( 95 % confidence interval , -0.0496 to -0.0073 ) , and baseline affective depression was associated with an excess decline in CD4 count of -0.0236 x 10(9)/L per year ( 95 % confidence interval , -0.0464 to -0.0008 ) . Neither overall depression nor affective depression was significantly associated with earlier AIDS diagnosis or earlier mortality . CONCLUSIONS Overall depression and affective depression predicted a more rapid decline in CD4 lymphocyte counts ; this association was not attributable to baseline physiological differences . While the mechanism of the association remains unknown and can not be addressed directly by this study , the data suggest that it can be explained neither as simply a reflection of perceived somatic symptoms nor as the result of differences in recreational drug and alcohol use . Further study is necessary to determine whether treating depression can alter the course of HIV infection |
2,241 | 23,899,569 | Conclusions : Short-term metformin treatment appears to moderately affect weight reduction in severely obese children and adolescents , with a concomitant improvement in fasting insulin sensitivity . | Objective : Childhood obesity has become epidemic and has been accompanied by an increase in prevalence of type 2 diabetes ( T2DM ) in youth .
Addressing obesity and insulin resistance by drug treatment represents a rational strategy for the prevention of T2DM .
A systematic review was performed to evaluate the effectiveness of metformin in reducing weight and ameliorating insulin resistance in obese nondiabetic children . | Objectives . The prevalence of type 2 diabetes in American adolescents has increased markedly during the past generation . Although the factors that contribute to the development of type 2 diabetes are complex and not wholly eluci date d , the triad of severe obesity , hyperinsulinemia , and a family history of type 2 diabetes places a child at an increased risk for development of the disease . Current approaches to the prevention of type 2 diabetes , including dietary counseling and exercise , have had limited success . We reasoned that drugs that increase glucose tolerance in diabetic patients might prove useful in preventing the progression to glucose intolerance in high-risk patients . To that end , we conducted a double-blind , placebo-controlled study of the effects of metformin on body mass index ( BMI ) , serum leptin , glucose tolerance , and serum lipids in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes . Methods . The study population consisted of 29 white and black adolescents aged 12 to 19 years . All had BMI s exceeding 30 kg/m2 . Criteria for enrollment included : 1 ) a fasting insulin concentration exceeding 15 μU/mL ; and 2 ) at least 1 first- or second-degree relative with type 2 diabetes . All patients had fasting plasma glucose concentrations < 110 mg% and hemoglobin A1c concentrations ≤6.0 % . All had normal linear growth and sexual development for age , with no marked hirsutism , severe acne , or menstrual irregularities characteristic of polycystic ovary syndrome . Eight participants had acanthosis nigricans . After baseline laboratory studies including a rapidly sample d intravenous glucose tolerance test , patients were r and omized to receive metformin ( 500 mg twice daily ) or a placebo for a total of 6 months . The effects of metformin on BMI st and ard deviation score , serum leptin , glucose tolerance , and serum lipids were analyzed . The study was double-blinded and included no specific dietary restrictions . Results . Metformin caused a decline of 0.12 st and ard deviation in BMI in study participants ( −1.3 % from baseline ) , and a 5.5 % reduction in serum leptin in girls . In contrast , BMI and serum leptin rose 0.23 st and ard deviation ( 2.3 % ) and 16.2 % , respectively , in the placebo group during the treatment period . Metformin caused a progressive decline in fasting blood glucose ( from a mean of 84.9 to 75.1 mg% ) and a reduction in fasting insulin levels ( from 31.3 to 19.3 μU/mL ) . In contrast , fasting glucose levels in the placebo group rose slightly from 77.2 to 82.3 mg% , and fasting insulin levels did not change . Insulin sensitivity , as assessed by the ratio of fasting insulin to glucose concentrations and the quantitative insulin sensitivity check index ( 1/[log fasting insulin + log fasting glucose ] ) and homeostasis model assessment insulin resistance index ( fasting insulin × fasting glucose/22.5 ) indices , increased slightly in the metformin-treated participants . However , the insulin sensitivity measured using Bergman 's minimal model did not change . There were also no significant changes in glucose effectiveness , hemoglobin A1c , serum lipids , or serum lactate in the metformin or placebo groups . Metformin was tolerated well by the majority of patients . Transient abdominal discomfort or diarrhea occurred in 40 % of treated participants ; there were no episodes of vomiting or lactic acidosis . Conclusions . The treatment of obesity and insulin resistance in adults often proves ineffective because the vicious cycle leading to type 2 diabetes may have become entrenched and , to some extent , may be irreversible . Early detection and therapy of the obese adolescent with a family history of type 2 diabetes may interrupt the cycle of weight gain and insulin resistance that leads to glucose intolerance in adulthood . Through its ability to reduce fasting blood glucose and insulin concentrations and to moderate weight gain , metformin might complement the effects of dietary and exercise counseling and reduce the risk of type 2 diabetes in selected patients Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors . The " gold st and ard " glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo , but neither is easily implemented in large studies . Thus , it is of interest to develop a simple , accurate method for assessing insulin sensitivity that is useful for clinical investigations . We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sample d iv glucose tolerance tests on 28 nonobese , 13 obese , and 15 type 2 diabetic subjects . We obtained correlations between indexes of insulin sensitivity from glucose clamp studies ( SI(Clamp ) ) and minimal model analysis ( SI(MM ) ) that were comparable to previous reports ( r = 0.57 ) . We performed a sensitivity analysis on our data and discovered that physiological steady state values [ i.e. fasting insulin ( I(0 ) ) and glucose ( G(0 ) ) ] contain critical information about insulin sensitivity . We defined a quantitative insulin sensitivity check index ( QUICKI = 1/[log(I(0 ) ) + log(G(0 ) ) ] ) that has substantially better correlation with SI(Clamp ) ( r = 0.78 ) than the correlation we observed between SI(MM ) and SI(Clamp ) . Moreover , we observed a comparable overall correlation between QUICKI and SI(Clamp ) in a totally independent group of 21 obese and 14 nonobese subjects from another institution . We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research OBJECTIVE Metformin can decrease adiposity and ameliorate obesity-related comorbid conditions , including abnormalities in glucose homeostasis in adolescents , but there are few data evaluating the efficacy of metformin among younger children . Our objective was to determine whether metformin treatment causes weight loss and improves obesity-related comorbidities in obese children , who are insulin-resistant . RESEARCH DESIGN AND METHODS This study was a r and omized double-blind placebo-controlled trial consisting of 100 severely obese ( mean BMI 34.6 ± 6.6 kg/m2 ) insulin-resistant children aged 6–12 years , r and omized to 1,000 mg metformin ( n = 53 ) or placebo ( n = 47 ) twice daily for 6 months , followed by open-label metformin treatment for 6 months . All children and their parents participated in a monthly dietitian-administered weight-reduction program . RESULTS Eighty-five percent completed the 6-month r and omized phase . Children prescribed metformin had significantly greater decreases in BMI ( difference −1.09 kg/m2 , CI −1.87 to −0.31 , P = 0.006 ) , body weight ( difference −3.38 kg , CI −5.2 to −1.57 , P < 0.001 ) , BMI Z score ( difference between metformin and placebo groups −0.07 , CI −0.12 to −0.01 , P = 0.02 ) , and fat mass ( difference −1.40 kg , CI −2.74 to −0.06 , P = 0.04 ) . Fasting plasma glucose ( P = 0.007 ) and homeostasis model assessment ( HOMA ) insulin resistance index ( P = 0.006 ) also improved more in metformin-treated children than in placebo-treated children . Gastrointestinal symptoms were significantly more prevalent in metformin-treated children , which limited maximal tolerated dosage in 17 % . During the 6-month open-label phase , children treated previously with placebo decreased their BMI Z score ; those treated continuously with metformin did not significantly change BMI Z score further . CONCLUSIONS Metformin had modest but favorable effects on body weight , body composition , and glucose homeostasis in obese insulin-resistant children participating in a low-intensity weight-reduction program OBJECTIVE To study whether metformin reduces obesity , homeostasis model assessment for insulin resistance index ( HOMA-IR ) , and the metabolic syndrome ( MtS ) in obese European adolescents in addition to previous unsuccessful lifestyle intervention . DESIGN AND METHODS After 6 months of multiprofessional lifestyle intervention , 70 out of 86 adolescents without improvement in body mass index ( BMI ) and HOMA-IR were r and omized into either the placebo ( n=34 ) or the metformin group ( 2 × 500 mg/day , n=36 ) in addition to ongoing lifestyle intervention for another 6 months . RESULTS Age was 13.8 years , BMI was 33.1 kg/m(2 ) , 65 % were female , and 89 % were Caucasians . During lifestyle intervention alone , BMI and HOMA-IR deteriorated significantly . In the subsequent medication period , HOMA-IR and fasting insulin improved similarly in the placebo and metformin groups ( HOMA-IR decreased 73 vs 54 % respectively in metformin versus placebo ; P=0.048 ) , but BMI remained unchanged . The insulin sensitivity index , however , only improved in the metformin group . High fasting insulin is correlated with a subsequent BMI increase irrespective of the medication . MtS remained unchanged . CONCLUSIONS Obese European adolescents ' insulin sensitivity improved without weight change during placebo or metformin intervention in addition to lifestyle intervention . Most differences did not reach statistical significance , probably due to improved compliance with lifestyle intervention as a placebo effect . In addition , the metformin dose may be too low Background The efficacy of pharmacological treatment in controlling childhood obesity is controversial . We aim ed to compare the effects of three types of drug regimens and placebo on generalized and abdominal obesity among obese children and adolescents who did not succeed to lose weight 3 months after lifestyle modification ( diet and exercise ) . Methods This triple-masked r and omized clinical trial was conducted among 180 participants aged 10–16 years . They were assigned r and omly to 4 groups of equal number to receive metformin , fluoxetine , a combination of the two drugs , or placebo . The trial lasted for 12 weeks and participants were followed up for an additional 12-week period . Results Overall , 91.1 % ( n=164 ) of the enrolled participants completed the trial . After the 12-week trial , the body mass index decreased significantly in all groups receiving medications [ approximately −1.2 ( 0.2 ) kg/m2 , P<0.05 ] . This decrease was not significant in the placebo group . Waist circumference decreased significantly in the groups receiving metformin [ −2.1 ( 0.4 ) cm , P=0.03 ) ] as well as in the group receiving a combination therapy of metformin and fluoxetine [ −2.5 ( 0.4 ) cm , P=0.01 ) ] . In the 24-week follow-up study , these anthropometric indexes were lower than the baseline in the group that had received a combination therapy of metformin and fluoxetine . No serious drug side-effects were reported . Conclusions A limited period of such treatment may help weight control , and might be used to encourage those children who have been refractory to weight loss for continuing the non-pharmacological programs . Our findings should be confirmed in future studies with a longer follow-up period BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P<0.001 ) in the intervention group . The reduction in the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects BACKGROUND Despite the increasing prevalence of type 2 diabetes in youth , there are few data to guide treatment . We compared the efficacy of three treatment regimens to achieve durable glycemic control in children and adolescents with recent-onset type 2 diabetes . METHODS Eligible patients 10 to 17 years of age were treated with metformin ( at a dose of 1000 mg twice daily ) to attain a glycated hemoglobin level of less than 8 % and were r and omly assigned to continued treatment with metformin alone or to metformin combined with rosiglitazone ( 4 mg twice a day ) or a lifestyle-intervention program focusing on weight loss through eating and activity behaviors . The primary outcome was loss of glycemic control , defined as a glycated hemoglobin level of at least 8 % for 6 months or sustained metabolic decompensation requiring insulin . RESULTS Of the 699 r and omly assigned participants ( mean duration of diagnosed type 2 diabetes , 7.8 months ) , 319 ( 45.6 % ) reached the primary outcome over an average follow-up of 3.86 years . Rates of failure were 51.7 % ( 120 of 232 participants ) , 38.6 % ( 90 of 233 ) , and 46.6 % ( 109 of 234 ) for metformin alone , metformin plus rosiglitazone , and metformin plus lifestyle intervention , respectively . Metformin plus rosiglitazone was superior to metformin alone ( P=0.006 ) ; metformin plus lifestyle intervention was intermediate but not significantly different from metformin alone or metformin plus rosiglitazone . Prespecified analyses according to sex and race or ethnic group showed differences in sustained effectiveness , with metformin alone least effective in non-Hispanic black participants and metformin plus rosiglitazone most effective in girls . Serious adverse events were reported in 19.2 % of participants . CONCLUSIONS Monotherapy with metformin was associated with durable glycemic control in approximately half of children and adolescents with type 2 diabetes . The addition of rosiglitazone , but not an intensive lifestyle intervention , was superior to metformin alone . ( Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others ; TODAY Clinical Trials.gov number , NCT00081328 . ) Abstract Objective : To determine if metformin improves markers of inflammation , thrombosis , and intrahepatic fat contents in children with uncomplicated obesity . Methods : Obese children with normal glucose tolerance but elevated highly sensitive C-reactive protein ( hsCRP ) and /or fibrinogen concentrations ( > 2 st and ard deviations ) were r and omized to structured diet/exercise or diet/exercise and metformin for 6 months . Blood sample s , dual energy X-ray absorptiometry data , and liver magnetic resonance images were obtained . Results : Forty-two of 66 recruited children ( 7–18 years ) completed 6 months . Weight loss was modest but more pronounced in the metformin group ( –4.9±1.0 kg ) than in the diet/exercise group ( –1.7±1.1 kg , p<0.03 ) , whereas hsCRP and fibrinogen decreased more in the diet/exercise pubertal group . Baseline intrahepatic fat was high but decreased only in the diet/exercise ( not metformin ) pubertal group . Conclusions : Six months of metformin therapy improved weight loss and reduced abdominal adiposity , but did not enhance the beneficial effect of diet and exercise on markers related to inflammation , thrombosis , or hepatic fat in obese children with normal glucose tolerance PURPOSE Obesity in adolescence increases the risk for early adult cardiovascular disease . We recently showed that 6 months of diet , exercise , and metformin result ed in reductions in adiposity and that diet/exercise alone reduced proinflammatory factors and intrahepatic fat in pubertal children with uncomplicated obesity . The purpose of the present study was to determine whether changes in cardiorespiratory fitness ( CRF ) after 6 months of structured diet and exercise ( DE ) or DE plus metformin are related to the previously observed changes in adiposity , markers of inflammation , and intrahepatic fat . METHODS Sixteen obese pubertal adolescents between the ages of 10 and 17 were r and omized into a structured lifestyle program consisting of DE or DE plus metformin . Subjects performed aerobic and resistance exercise 3 d·wk⁻¹ , 30 min per session . Cycle ergometer maximal oxygen consumption ( V˙O2max ) , body composition , blood markers ( glucose , insulin , homeostatic model assessment -insulin resistance , interleukin-6 , hsCRP ) , and intrahepatic fat were measured at baseline and 6 months . RESULTS In the cohort , as whole-body weight decreased by 4.0 % ( P = 0.009 ) , body mass index decreased by 4.9 % ( P = 0.003 ) , percent body fat decreased by 8.8 % ( P < 0.001 ) , and V˙O2max improved in 10 of 16 subjects . The addition of metformin provided no further effect on body composition , CRF , or inflammatory factors . More favorable changes in adiposity , adiponectin , and a trend toward blood glucose and interleukin-6 concentrations ( P = 0.07 ) were observed in subjects who increased V˙O2max at 6 months ( n = 10 ) compared with no change in these variables in those who did not improve V˙O2max . CONCLUSIONS Metformin did not provide benefits above lifestyle modification for improving CRF in obese adolescents . Improvements in V˙O2max seem to be associated with more favorable metabolic outcomes CONTEXT Childhood obesity is increasingly associated with type 2 diabetes ( T2D ) . Metformin reduces the risk for T2D in adult obese nondiabetic patients , but the evidence in obese children and young people is inconclusive . OBJECTIVE The objective of the study was to assess the effect of metformin on body mass index sd score ( BMI -SDS ) , metabolic risk factors , and adipokines . DESIGN This was a prospect i ve , r and omized , double-blind , placebo-controlled trial . SETTING The study was conducted at six pediatric endocrine centers in the United Kingdom . PARTICIPANTS One hundred fifty-one obese children and young people with hyperinsulinemia and /or impaired fasting glucose or impaired glucose tolerance ( metformin : 74 , placebo : 77 ) . The study was comprised of 67.5 % females , 65.6 % postpubertal individuals , and 23.8 % British Asian or Afro-Caribbean participants . The age range was 8 - 18 yr , the mean age was 13.7 ( SD 2.3 ) yr , and the mean BMI -SDS was + 3.4 ( SD 0.5 ) . INTERVENTIONS The intervention included metformin 1 g in the morning and 500 mg in the evening vs. placebo for 6 months . MAIN OUTCOME MEASURE The main outcome measure was a reduction in BMI -SDS at 6 months . Secondary outcomes included insulin and glucose levels from oral glucose tolerance tests , alanine aminotransferase ( ALT ) , and adiponectin to leptin ratio ( ALR ) at 3 and 6 months . RESULTS Metformin was associated with a significant reduction in BMI -SDS compared with placebo at 6 months [ mean difference -0.1 SD ( 95 % confidence interval -0.18 to -0.02 ) , P = 0.02 ] . Significant improvements at 3 months were found in the metformin group : fasting glucose , -0.16 mmol/liter ( -0.31 to -0.00 ) , P = 0.047 ; ALT , 19 % ( 5 - 36 % ) , P = 0.008 ; and ALR , 32 % ( 4 - 67 % ) , P = 0.02 . CONCLUSIONS Metformin therapy has a beneficial treatment effect over placebo for BMI -SDS , fasting glucose , ALT , and ALR ratio at 3 months , with changes in BMI -SDS sustained at 6 months 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 OBJECTIVE To evaluate whether metformin , when added to a program of personal goal setting , improves weight loss and clinical status in obese adolescents . STUDY DESIGN In a r and omized double-blind placebo controlled trial , 85 adolescents with insulin resistance were r and omized to receive metformin ( 70 % ) or placebo ( 30 % ) , along with monthly goal setting for diet and exercise modification . Anthropometric measures , fasting blood analysis , and glucose tolerance tests were performed at baseline and 6 months . RESULTS Mean age was 15.7 years . Mean body mass index ( BMI ) was 39.7 kg/m(2 ) . 71 % were female , 58 % were Hispanic , and 34 % were African-American . 76 % of participants completed the study . Goal setting alone did not result in significant weight loss . In addition , there were no group differences between metformin and placebo in weight loss or measures of glucose metabolism . However , among females taking metformin , there was a significant decrease in BMI not seen in the placebo group . Furthermore , metformin adherence , when accompanied by lifestyle change , was a predictor of BMI decrease of 5 % or more . 60 % of 10 subjects who adhered to metformin and decreased portion size decreased BMI by > 5 % . CONCLUSIONS In this group of predominately minority adolescents , monthly goal setting alone did not lead to weight loss . Although the addition of metformin had no effect on weight loss overall , the agent did significantly increase weight loss among females and weight loss was predicted by degree of metformin adherence . However , weight loss was only found in those participants also reporting lifestyle change , particularly a decrease in portion sizes . These results suggest that metformin may be a useful agent to promote short-term weight loss among girls making modest lifestyle changes Hyperinsulinemia and insulin resistance are common features of obesity in humans and experimental animals . It has been demonstrated that metformin , an antihyperglycemic agent , decreases hyperinsulinemia and insulin resistance leading to decreased adiposity in obese and non-insulin-dependent diabetes mellitus ( NIDDM ) adults . To evaluate the antiobesity effect of metformin , we conducted a r and omized double-blind placebo controlled trial in 24 hyperinsulinemic nondiabetic obese adolescents ( body mass index [ BMI ] > 30 kg/m(2 ) ) . All subjects were placed on a low-calorie ( 1,500 kcal for women and 1,800 kcal for men ) meal plan . After an initial 1-week lead-in period , 12 subjects ( mean + /- SE for age and BMI , 15.6 + /- 0.4 and 41.2 + /- 1.8 , respectively ) received metformin ( 850 mg twice daily ) for 8 weeks , and 12 subjects ( mean + /- SE for age and BMI , 15.7 + /- 0.5 and 40.8 + /- 1.4 , respectively ) received placebo . Compared to the placebo group , the metformin group had greater weight loss ( 6.5 % + /- 0.8 % v 3.8 + /- 0.4 % , P < .01 ) , greater decrease in body fat ( P < .001 ) , greater increase in fat-free mass to body fat ratio ( P < .005 ) , and greater attenuation of area under the curve ( AUC ) insulin response to an oral glucose tolerance test ( P < .001 ) . This was associated with enhanced insulin sensitivity , as determined by the fasting plasma glucose : insulin , 2-hour glucose : insulin , and AUC glucose : AUC insulin ratios , in the metformin group compared to controls ( P < .01 ) . This corresponded to a significant reduction in plasma leptin ( P < .005 ) , cholesterol , triglycerides , and free fatty acid ( FFA ) levels ( P < .05 ) only in the metformin-treated subjects . Combined metformin treatment and low-calorie diet had a significant antiobesity effect in hyperinsulinemic obese adolescents compared to a low-calorie diet alone BACKGROUND Metformin has been proffered as a therapy for adolescent obesity , although long-term controlled studies have not been reported . OBJECTIVE To test the hypothesis that 48 weeks of daily metformin hydrochloride extended release ( XR ) therapy will reduce body mass index ( BMI ) in obese adolescents , as compared with placebo . DESIGN Multicenter , r and omized , double-blind , placebo-controlled clinical trial . SETTING The 6 centers of the Glaser Pediatric Research Network from October 2003 to August 2007 . PARTICIPANTS Obese ( BMI > or = 95th percentile ) adolescents ( aged 13 - 18 years ) were r and omly assigned to the intervention ( n = 39 ) or placebo groups . Intervention Following a 1-month run-in period , subjects following a lifestyle intervention program were r and omized 1:1 to 48 weeks ' treatment with metformin hydrochloride XR , 2000 mg once daily , or an identical placebo . Subjects were monitored for an additional 48 weeks . Main Outcome Measure Change in BMI , adjusted for site , sex , race , ethnicity , and age and metformin vs placebo . RESULTS After 48 weeks , mean ( SE ) adjusted BMI increased 0.2 ( 0.5 ) in the placebo group and decreased 0.9 ( 0.5 ) in the metformin XR group ( P = .03 ) . This difference persisted for 12 to 24 weeks after cessation of treatment . No significant effects of metformin on body composition , abdominal fat , or insulin indices were observed . CONCLUSION Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program . TRIAL REGISTRATION clinical trials.gov Identifiers : NCT00209482 and NCT00120146 CONTEXT Metformin therapy for adults and children with type 2 diabetes is well established . However , its role in the treatment of insulin resistance and obesity in children and adolescents is less clearly defined . OBJECTIVE We assessed the effect of metformin on body composition and insulin sensitivity in pediatric subjects with exogenous obesity . DESIGN AND SETTING Patients referred to a pediatric endocrine clinic were enrolled in a r and omized , double-blind , crossover trial . PATIENTS Twenty-eight patients ( 13 males ) aged 9 - 18 yr participated in the study . INTERVENTION Patients received metformin ( 1 g twice daily ) and placebo for 6 months , each with a 2-wk washout period . MAIN OUTCOME MEASURES Body composition ( anthropometry , dual-energy x-ray absorptiometry , and abdominal magnetic resonance imaging ) , and insulin sensitivity ( Si ; minimal model , fasting insulin and glucose ) were measured at baseline and 6 and 12 months . RESULTS Mean age of subjects at baseline was 12.5 + /- 2.2 yr , median body mass index z-score 2.54 ( range , 1.93 - 2.85 ) . Metformin had a greater treatment effect over placebo for weight ( -4.35 kg , P = 0.02 ) , body mass index ( -1.26 kg/m(2 ) , P = 0.002 ) , waist circumference ( -2.8 cm , P = 0.003 ) , sc abdominal adipose tissue ( -52.5 cm(2 ) , P = 0.002 ) , and fasting insulin ( -2.2 mU/liter , P = 0.011 ) . Si improved in 45 % of subjects while on metformin and 27 % of subjects while on placebo ( P = 0.21 ) . CONCLUSIONS Metformin therapy for obese insulin-resistant pediatric patients results in significant improvement in body composition and fasting insulin . Although improvement in Si was noted in many individuals , Si was a less useful parameter for analysis of group data , possibly because of effects of variable compliance and changing Si during puberty OBJECTIVE Several methods have been proposed to evaluate insulin sensitivity from the data obtained from the oral glucose tolerance test ( OGTT ) . However , the validity of these indices has not been rigorously evaluated by comparing them with the direct measurement of insulin sensitivity obtained with the euglycemic insulin clamp technique . In this study , we compare various insulin sensitivity indices derived from the OGTT with whole-body insulin sensitivity measured by the euglycemic insulin clamp technique . RESEARCH DESIGN AND METHODS In this study , 153 subjects ( 66 men and 87 women , aged 18 - 71 years , BMI 20 - 65 kg/m2 ) with varying degrees of glucose tolerance ( 62 subjects with normal glucose tolerance , 31 subjects with impaired glucose tolerance , and 60 subjects with type 2 diabetes ) were studied . After a 10-h overnight fast , all subjects underwent , in r and om order , a 75-g OGTT and a euglycemic insulin clamp , which was performed with the infusion of [3 - 3H]glucose . The indices of insulin sensitivity derived from OGTT data and the euglycemic insulin clamp were compared by correlation analysis . RESULTS The mean plasma glucose concentration divided by the mean plasma insulin concentration during the OGTT displayed no correlation with the rate of whole-body glucose disposal during the euglycemic insulin clamp ( r = -0.02 , NS ) . From the OGTT , we developed an index of whole-body insulin sensitivity ( 10,000/square root of [ fasting glucose x fasting insulin ] x [ mean glucose x mean insulin during OGTT ] ) , which is highly correlated ( r = 0.73 , P < 0.0001 ) with the rate of whole-body glucose disposal during the euglycemic insulin clamp . CONCLUSIONS Previous methods used to derive an index of insulin sensitivity from the OGTT have relied on the ratio of plasma glucose to insulin concentration during the OGTT . Our results demonstrate the limitations of such an approach . We have derived a novel estimate of insulin sensitivity that is simple to calculate and provides a reasonable approximation of whole-body insulin sensitivity from the OGTT |
2,242 | 28,038,460 | No significant difference were noted between the groups regarding intraoperative complications , TME completeness and harvesting of lymph nodes .
Regarding the long-term survival data , the laparoscopic group was not inferior to laparotomy .
Some pooled data , such as 3-year DFS , 5-year OS and 5-year local recurrence were even superior for the laparoscopic group . | BACKGROUND Laparoscopic-assisted radical resection of rectal cancer was reported as advantageous compared to laparotomy resection .
However , this finding remains controversial , especially given the two recent r and omized controlled trials published on The Journal of the American Medical Association ( JAMA ) .
OBJECTIVE To perform a meta- analysis that compares the short-term and long-term outcomes of laparoscopic and open surgery for rectal cancer . | Background The role of laparoscopic resection ( LR ) in the management of extraperitoneal rectal cancer still is unclear . This study aim ed to compare perioperative and long-term results of laparoscopic and open resection ( OR ) for low and midrectal cancer . Methods A prospect i ve nonr and omized trial comparing patients su bmi tted to OR or LR for low and midrectal cancer at a single institution was conducted . Results The study included 191 consecutive patients : 98 patients who underwent LR and 93 who underwent OR . The mean follow-up period was 46.3 months for LR and 49.7 months for OR . The conversion rate for LR was 18.4 % . With the use of LR , the mean time for complete patient mobilization was shorter ( 1.7 vs 3.3 days ; p < 0.001 ) and patients were earlier in passing flatus ( 2.6 vs 3.9 days ; p < 0.001 ) and stools ( 3.8 vs 4.7 days ; p < 0.01 ) , and in resuming oral intake ( 3.4 vs 4.8 days ; p < 0.001 ) . The mean hospital stay was shorter for LR , but the difference did not reach significance ( 11.4 vs 13 days ) . Morbidity and mortality rates were similar : LR ( 24.4 % and 1 % ) and OR ( 23.6 % and 2.2 % ) . Laparoscopic patients presented a higher rate of anastomotic fistulas ( 13.5 % vs 5.1 % ) and reoperations ( 6.1 % vs 3.2 % ) but the difference was statistically nonsignificant . Laparoscopic resection presented a significantly lower local recurrence rate ( 3.2 % vs 12.6 % ; p < 0.05 ) . The cumulative survival and disease-free rates at 5 years were , respectively , 80 % and 65.4 % after LR and 68.9 % and 58.9 % after OR ( nonsignificant difference ) . Stage-by-stage comparison showed prolonged cumulative survival for stages III and IV cancer in LR ( 82.5 % vs 40.5 % ; p = 0.006 and 15.8 % vs 0 % ; p = 0.013 , respectively ) and a reduced rate of cancer-related death for stage III in LR ( 11.4 % vs 51.9 % ; p = 0.001 ) . Conclusions As compared with conventional open surgery , LR for low and midrectal cancer is characterized by a faster recovery and similar overall morbidity ( but a higher rate of anastomotic leakages ) , and does not present any adverse oncologic effect BACKGROUND Laparoscopic surgery as an alternative to open surgery in patients with rectal cancer has not yet been shown to be oncologically safe . The aim in the COlorectal cancer Laparoscopic or Open Resection ( COLOR II ) trial was to compare laparoscopic and open surgery in patients with rectal cancer . METHODS A non-inferiority phase 3 trial was undertaken at 30 centres and hospitals in eight countries . Patients ( aged ≥18 years ) with rectal cancer within 15 cm from the anal verge without evidence of distant metastases were r and omly assigned to either laparoscopic or open surgery in a 2:1 ratio , stratified by centre , location of tumour , and preoperative radiotherapy . The study was not masked . Secondary ( short-term ) outcomes -including operative findings , complications , mortality , and results at pathological examination-are reported here . Analysis was by modified intention to treat , excluding those patients with post-r and omisation exclusion criteria and for whom data were not available . This study is registered with Clinical Trials.gov , number NCT00297791 . FINDINGS The study was undertaken between Jan 20 , 2004 , and May 4 , 2010 . 1103 patients were r and omly assigned to the laparoscopic ( n=739 ) and open surgery groups ( n=364 ) , and 1044 were eligible for analyses ( 699 and 345 , respectively ) . Patients in the laparoscopic surgery group lost less blood than did those in the open surgery group ( median 200 mL [ IQR 100 - 400 ] vs 400 mL [ 200 - 700 ] , p<0·0001 ) ; however , laparoscopic procedures took longer ( 240 min [ 184 - 300 ] vs 188 min [ 150 - 240 ] ; p<0·0001 ) . In the laparoscopic surgery group , bowel function returned sooner ( 2·0 days [ 1·0 - 3·0 ] vs 3·0 days [ 2·0 - 4·0 ] ; p<0·0001 ) and hospital stay was shorter ( 8·0 days [ 6·0 - 13·0 ] vs 9·0 days [ 7·0 - 14·0 ] ; p=0·036 ) . Macroscopically , completeness of the resection was not different between groups ( 589 [ 88 % ] of 666 vs 303 [ 92 % ] of 331 ; p=0·250 ) . Positive circumferential resection margin ( < 2 mm ) was noted in 56 ( 10 % ) of 588 patients in the laparoscopic surgery group and 30 ( 10 % ) of 300 in the open surgery group ( p=0·850 ) . Median tumour distance to distal resection margin did not differ significantly between the groups ( 3·0 cm [ IQR 2·0 - 4·8 ] vs 3·0 cm [ 1·8 - 5·0 ] , respectively ; p=0·676 ) . In the laparoscopic and open surgery groups , morbidity ( 278 [ 40 % ] of 697 vs 128 [ 37 % ] of 345 , respectively ; p=0·424 ) and mortality ( eight [ 1 % ] of 699 vs six [ 2 % ] of 345 , respectively ; p=0·409 ) within 28 days after surgery were similar . INTERPRETATION In selected patients with rectal cancer treated by skilled surgeons , laparoscopic surgery result ed in similar safety , resection margins , and completeness of resection to that of open surgery , and recovery was improved after laparoscopic surgery . Results for the primary endpoint-locoregional recurrence-are expected by the end of 2013 . FUNDING Ethicon Endo-Surgery Europe , Swedish Cancer Foundation , West Gothia Region , Sahlgrenska University Hospital BACKGROUND Compared with open resection , laparoscopic resection of rectal cancers is associated with improved short-term outcomes , but high-level evidence showing similar long-term outcomes is scarce . We aim ed to compare survival outcomes of laparoscopic surgery with open surgery for patients with mid-rectal or low-rectal cancer . METHODS The Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy ( COREAN ) trial was an open-label , non-inferiority , r and omised controlled trial done between April 4 , 2006 , and Aug 26 , 2009 , at three centres in Korea . Patients ( aged 18 - 80 years ) with cT3N0 - 2M0 mid-rectal or low-rectal cancer who had received preoperative chemoradiotherapy were r and omly assigned ( 1:1 ) to receive either open or laparoscopic surgery . R and omisation was stratified by sex and preoperative chemotherapy regimen . Investigators were masked to the r and omisation sequence ; patients and clinicians were not masked to the treatment assignments . The primary endpoint was 3 year disease-free survival , with a non-inferiority margin of 15 % . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00470951 . FINDINGS We r and omly assigned 340 patients to receive either open surgery ( n=170 ) or laparoscopic surgery ( n=170 ) . 3 year disease-free survival was 72·5 % ( 95 % CI 65·0 - 78·6 ) for the open surgery group and 79·2 % ( 72·3 - 84·6 ) for the laparoscopic surgery group , with a difference that was lower than the prespecified non-inferiority margin ( -6·7 % , 95 % CI -15·8 to 2·4 ; p<0·0001 ) . 25 ( 15 % ) patients died in the open group and 20 ( 12 % ) died in the laparoscopic group . No deaths were treatment related . INTERPRETATION Our results show that laparoscopic resection for locally advanced rectal cancer after preoperative chemoradiotherapy provides similar outcomes for disease-free survival as open resection , thus justifying its use . FUNDING National Cancer Center , South Korea Purpose Laparoscopic surgery of colon cancer has been accepted to be oncologically adequate compared with open resection . However , the situation in rectal cancer remains unclear , because anatomy and complex surgical procedures might specifically influence the long-term outcome . This study was design ed to analyze perioperative and long-term outcome of patients with rectal cancer after laparoscopic vs. open access surgery . Methods A total of 389 patients ( 1998–2005 ) were prospect ively analyzed ; 114 patients had laparoscopic beginning , and 25 patients had conversion and were separately analyzed . Eighty-nine patients remained in the laparoscopic group and 275 had open access surgery . Results Both groups were comparable regarding age , gender , tumor localization , stage , and complications . Differences were found in harvested lymph nodes ( laparoscopic 13.5/open access 16.9 ; P = 0.001 ) and hospitalization ( 15.1/18.7 days ; P = 0.037 ) . Local recurrence rate and metachronous metastasis were comparable . In patients with deep anterior resection with total mesenteric excision , favorable long-term survival in the laparoscopic group was found ( P = 0.035 , log-rank ) . Conclusions Minimally invasive surgery is equivalent in the treatment of rectal cancer and shows advantages of shorter hospitalization and faster recovery . Especially in patients with low rectal cancer , minimally invasive surgery with exact preparation of the total mesenteric excision seems to be favorable compared with open access surgery BACKGROUND Laparoscopic resection of colorectal cancer is widely used . However , robust evidence to conclude that laparoscopic surgery and open surgery have similar outcomes in rectal cancer is lacking . A trial was design ed to compare 3-year rates of cancer recurrence in the pelvic or perineal area ( locoregional recurrence ) and survival after laparoscopic and open resection of rectal cancer . METHODS In this international trial conducted in 30 hospitals , we r and omly assigned patients with a solitary adenocarcinoma of the rectum within 15 cm of the anal verge , not invading adjacent tissues , and without distant metastases to undergo either laparoscopic or open surgery in a 2:1 ratio . The primary end point was locoregional recurrence 3 years after the index surgery . Secondary end points included disease-free and overall survival . RESULTS A total of 1044 patients were included ( 699 in the laparoscopic-surgery group and 345 in the open-surgery group ) . At 3 years , the locoregional recurrence rate was 5.0 % in the two groups ( difference , 0 percentage points ; 90 % confidence interval [ CI ] , -2.6 to 2.6 ) . Disease-free survival rates were 74.8 % in the laparoscopic-surgery group and 70.8 % in the open-surgery group ( difference , 4.0 percentage points ; 95 % CI , -1.9 to 9.9 ) . Overall survival rates were 86.7 % in the laparoscopic-surgery group and 83.6 % in the open-surgery group ( difference , 3.1 percentage points ; 95 % CI , -1.6 to 7.8 ) . CONCLUSIONS Laparoscopic surgery in patients with rectal cancer was associated with rates of locoregional recurrence and disease-free and overall survival similar to those for open surgery . ( Funded by Ethicon Endo-Surgery Europe and others ; COLOR II Clinical Trials.gov number , NCT00297791 . ) Purpose This study was design ed to evaluate the impact of laparoscopic rectal resection on short-term postoperative morbidity and costs . Methods A total of 168 patients with rectal cancer were r and omly assigned to laparoscopic ( n = 83 ) or open ( n = 85 ) resection . Outcome parameters were : postoperative morbidity , length of hospital stay , quality of life , long-term survival , and local recurrences . The mean follow-up period was 53.6 months . Cost-benefit analysis was based on hospital costs . Results Operative time was 53 minutes longer in the laparoscopic group ( P < 0.0001 ) . Postoperative morbidity rate was 28.9 percent in the laparoscopic vs. 40 percent in the open group ( P = 0.18 ) . The mean length of hospital stay was 10 ( 4.9 ) days in the laparoscopic group and 13.6 ( 10 ) days in the open group ( P = 0.004 ) . Local recurrence rate and five-year survival were similar in both groups ; however , the limited number of patients does not allow firm conclusions . Quality of life was better in the laparoscopic group only in the first year after surgery ( P < 0.0001 ) . The additional charge in the laparoscopic group was $ 1,748 per patient r and omized ( $ 1,194 the result of surgical instruments and $ 554 the result of longer operative time ) . The saving in the laparoscopic group was $ 1,396 per patient r and omized ( $ 647 the result of shorter length of hospital stay and $ 749 the result of the lower cost of postoperative complications ) . The net balance result ed in $ 351 extra cost per patient r and omly allocated to the laparoscopic group . Conclusions Short-term postoperative morbidity was similar in the two groups . Laparoscopic resection reduced length of hospital stay , improved first-year quality of life , and slightly increased hospital costs IMPORTANCE Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete , particularly for patients with more advanced-stage disease . OBJECTIVE To determine whether laparoscopic resection is noninferior to open resection , as determined by gross pathologic and histologic evaluation of the resected proctectomy specimen . DESIGN , SETTING , AND PARTICIPANTS A multicenter , balanced , noninferiority , r and omized trial enrolled patients between October 2008 and September 2013 . The trial was conducted by credentialed surgeons from 35 institutions in the United States and Canada . A total of 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were r and omized after completion of neoadjuvant therapy to laparoscopic or open resection . INTERVENTIONS St and ard laparoscopic and open approaches were performed by the credentialed surgeons . MAIN OUTCOMES AND MEASURES The primary outcome assessing efficacy was a composite of circumferential radial margin greater than 1 mm , distal margin without tumor , and completeness of total mesorectal excision . A 6 % noninferiority margin was chosen according to clinical relevance estimation . RESULTS Two hundred forty patients with laparoscopic resection and 222 with open resection were evaluable for analysis of the 486 enrolled . Successful resection occurred in 81.7 % of laparoscopic resection cases ( 95 % CI , 76.8%-86.6 % ) and 86.9 % of open resection cases ( 95 % CI , 82.5%-91.4 % ) and did not support noninferiority ( difference , -5.3 % ; 1-sided 95 % CI , -10.8 % to ∞ ; P for noninferiority = .41 ) . Patients underwent low anterior resection ( 76.7 % ) or abdominoperineal resection ( 23.3 % ) . Conversion to open resection occurred in 11.3 % of patients . Operative time was significantly longer for laparoscopic resection ( mean , 266.2 vs 220.6 minutes ; mean difference , 45.5 minutes ; 95 % CI , 27.7 - 63.4 ; P < .001 ) . Length of stay ( 7.3 vs 7.0 days ; mean difference , 0.3 days ; 95 % CI , -0.6 to 1.1 ) , readmission within 30 days ( 3.3 % vs 4.1 % ; difference , -0.7 % ; 95 % CI , -4.2 % to 2.7 % ) , and severe complications ( 22.5 % vs 22.1 % ; difference , 0.4 % ; 95 % CI , -4.2 % to 2.7 % ) did not differ significantly . Quality of the total mesorectal excision specimen in 462 operated and analyzed surgeries was complete ( 77 % ) and nearly complete ( 16.5 % ) in 93.5 % of the cases . Negative circumferential radial margin was observed in 90 % of the overall group ( 87.9 % laparoscopic resection and 92.3 % open resection ; P = .11 ) . Distal margin result was negative in more than 98 % of patients irrespective of type of surgery ( P = .91 ) . CONCLUSIONS AND RELEVANCE Among patients with stage II or III rectal cancer , the use of laparoscopic resection compared with open resection failed to meet the criterion for noninferiority for pathologic outcomes . Pending clinical oncologic outcomes , the findings do not support the use of laparoscopic resection in these patients . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00726622 AIM To evaluate the feasibility of laparoscopic resection of rectal carcinoma and to compare the short-term outcome of laparoscopic procedure with conventional open surgery for rectal cancer . METHODS Thirty-eight patients with rectal cancer were included in a prospect i ve non-r and omized study . The patients were assigned to laparoscopic ( n=18 ) or open ( n=18 ) colorectal resection . Case selection , surgical technique , and clinical and pathological results were review ed . RESULTS The operative time was longer in laparoscopic resection group ( LAP ) than in open resection group ( 189+/-18 min vs 146+/-22 min , P<0.05 ) . Intraoperative blood loss and postoperative complications were less in LAP resection group than in open resection group . An earlier return of bowel motility was observed after laparoscopic surgery . The overall postoperative morbidity was 5.6 % in the LAP resection group and 27.8 % in open resection group ( P<0.05 ) . No anastomotic leakage was found in both groups . The pathologic examination showed that the length of the resected specimen , the mean number of harvested lymph nodes in laparoscopic resection group were comparable to those in open resection group . CONCLUSION Laparoscopic total mesorectal excision ( TME ) for rectal cancer is a feasible but technically dem and ing procedure . The present study demonstrates the safety of the procedure , while oncologic results are comparable to the open surgery , with a favorable short-term outcome Purpose This study was design ed to compare the outcomes of laparoscopic anterior resection with open operation for mid and upper rectal cancer . Methods A total of 265 patients who underwent elective laparoscopic or open anterior resection for cancer of the mid and upper rectum from June 2000 to December 2004 were included . Data about the patients ’ demographics , operative details , postoperative outcome , and disease status were collected prospect ively . Comparison of the outcome between laparoscopic and open resection was performed . Results The median age of the 265 patients was 69 ( range , 27–91 ) years , and laparoscopic anterior resection was performed in 98 patients ( 37 percent ) . There was no difference in the age , gender , comorbidities , and level of tumor between the two groups . The operating time was longer in the laparoscopic group ( 200 vs. 127 minutes ; P < 0.01 ) , but the blood loss was less ( 200 vs. 250 ml ; P = 0.027 ) . The overall operative mortality was 1.8 percent , and the complication rate was 27.9 percent . Significantly more patients with early diseases ( Stage I and Stage II ) were operated with laparoscopic approach . There was no difference in the mortality or morbidity between the two groups . Anastomotic leakage occurred in five patients with open resection and one with laparoscopic resection ( P = 0.418 ) . Patients with laparoscopic resection had an earlier return of bowel function and earlier resumption of diet as well as a shorter median hospital stay ( 7 vs. 8 days ; P < 0.001 ) . With the median follow-up of the surviving patients for 21.2 months , the three-year local recurrence rates for those with open and laparoscopic resection were 4.9 and 3.3 percent , respectively ( P = 0.513 ) . In patients with Stage I and Stage II disease , the three-year cancer-specific survivals for open and laparoscopic resection were 89.8 and 88.6 percent , respectively ( P = 0.882 ) , whereas those of patients with Stage III disease were 65.6 and 55.5 percent , respectively ( P = 0.911 ) . Conclusions Laparoscopic anterior resection for mid and proximal rectal cancer is a safe option with short-term advantages compared with open operation . The oncologic outcomes of patients who underwent laparoscopic anterior resection were not compromised , with similar local recurrence rate and the cancer-specific survival rate as patients who underwent open resection Background : Laparoscopic resection of the rectum is still under scrutiny for its adequacy of oncological clearance . Aim : To assess lymph node yield after laparoscopic total mesorectal excision ( TME ) for rectal cancer as compared to the open approach . Methods : 74 patients with middle and low rectal cancer were prospect ively r and omized in two groups . Group A included 39 patients who had an open TME ( 35 with low anterior resection of the rectum ( LARR ) and 4 with abdominoperineal resection of the rectum ( APR ) ) . In group B , there were 34 patients who had a laparoscopic TME ( 27 with LARR and 7 with APR ) . 10 of the LARR patients in group A and 14 of the LARR patients in group B had a defunctioning ileostomy . All operations were performed by one surgeon or under his supervision . Results : Gender and age distribution were similar for both groups ( group A : 23 males ; mean age 69 ( 41–85 ) ; group B : 20 males ; mean age 72 ( 31–84 ) ) . The mean distance of the tumor from the dentate line was 7.6 cm ( 1–12 cm ) for group A and 6.1 cm ( 1–12 cm ) for group B. Anastomosis was formed at a mean distance of 5.5 cm ( 1.5–8.5 cm ) from the dentate line in group A and 3.5 cm ( 1–4.5 cm ) in group B. At histology , in group A there were 5 T4 tumors , 9 T3 , 10 T3 + ( < 1 mm distance from the circumferential resection margin ) , 13 T2 and 2 T1 . In group B , there were 3 T4 tumors , 14 T3 , 8 T3 + , 7 T2 and 2 T1 . Differences between groups were not significant . The mean number of lymph nodes retrieved in group A specimens was 19.2 ( 5–45 ) and in group B 19.2 ( 8–41 ) ( p = 0.2 ) . In group A , 3.9 ( 1–9 ) regional , 13.9 ( 3–34 ) intermediate and 1.5 ( 1–3 ) apical lymph nodes were retrieved . The respective values in group B were 3.7 ( 3–7 ) , 14.4 ( 4–33 ) and 1.3 ( 1–3 ) . Differences between groups were not significant . Also , the incidence of lymph node involvement by the tumor was not significantly different between groups ( group A : 23 ; group B : 19 ) . Conclusions : Laparoscopic resection of the rectum can achieve similar lymph node clearance to the open approach . Also , distribution of the lymph nodes along the resected specimens is similar between the two approaches Background The Laparoscopic approach has been applied to colorectal surgery for many years ; however , there are only a few reports on laparoscopic low and ultralow anterior resection with construction of coloanal anastomosis . This study compares open versus laparoscopic low and ultralow anterior resections , assesses the feasibility and efficacy of the laparoscopic approach of total mesorectal excision ( TME ) with anal sphincter preservation ( ASP ) , and analyzes the short-term results of patients with low rectal cancer . Methods We analyzed our experience via a prospect i ve , r and omized control trail . From June 2001 to September 2002 , 171 patients with low rectal cancer underwent TME with ASP , 82 by the laparoscopic procedure and 89 by the open technique . The lowest margin of tumors was below peritoneal reflection and 1.5–8 cm above the dentate line ( 1.5–4.9 cm in 104 cases and 5–8 cm in 67 cases ) . The grouping was r and omized . Results Results of operation , postoperative recovery , and short-term oncological follow-up were compared between 82 laparoscopic procedures and 89 controls who underwent open surgery during the same period . In the laparoscopic group , 30 patients in whom low anterior resection was performed had the anastomosis below peritoneal reflection and more than 2 cm above the dentate line , 27 patients in whom ultralow anterior resection was performed had anastomotic height within 2 cm of the dentate line , and 25 patients in whom coloanal anastomosis was performed had the anastomosis at or below the dentate line . In the open group , the numbers were 35 , 27 , and 27 , respectively . There was no statistical difference in operation time , administration of parenteral analgesics , start of food intake , and mortality rate between the two groups . However , blood loss was less , bowel function recovered earlier , and hospitalization time was shorter in the laparoscopic group . Conclusion Totally laparoscopic TME with ASP is feasible , and it is a minimally invasive technique with the benefits of much less blood loss during operation , earlier return of bowel function , and shorter hospitalization PURPOSE : The aim of the study is to assess the safety and oncologic feasibility of laparoscopic-assisted resection for rectal cancer vs open rectal resection as a phase II pilot study for a planned r and omized control trial . METHODS : A case-matched controlled prospect i ve analysis of 54 patients who underwent laparoscopic-assisted resection for stage I to III ( no T4 ) rectal cancer within 12 cm of the anal verge from 2002 to 2005 was performed . Patients were matched with contemporary patients who underwent open rectal cancer surgery ( n = 108 ) in a 1 to 2 fashion . The perioperative clinical outcomes , postoperative pathology , and oncologic outcomes were compared between the groups . RESULTS : The demographic data did not differ significantly between the groups . The laparoscopic group manifested early return of bowel function ( P = .003 ) . The complication rate was 22.2 % in the laparoscopic group and 32.4 % in the open group ( P = .178 ) . Local recurrence was similar ( 2.0 % laparoscopic , 4.2 % open , P = .417 ) . The 5-year overall and disease-free survival rate also were similar ( overall survival , 90.8 % laparoscopic , 88.5 % open , P = .261 ; disease-free survival , 80.8 % laparoscopic , 75.8 % open . P = .390 ) . CONCLUSION : The laparoscopic-assisted resection for rectal cancer was acceptable in terms of oncologic outcomes and perioperative clinical outcomes . The present data are the basis for a large-scale r and omized trial for comparison of laparoscopic and open rectal cancer surgeries ( American College of Surgeons Oncology Group Z6051 ) Background and aims Because definitive long-term results are not yet available , the oncological safety of laparoscopic surgery for treatment of rectal cancer remains unproven . The aim of this prospect i ve non-r and omised study was to assess the feasibility and short-term outcome of laparoscopic total mesorectal excision ( LTME ) after 25–30 Gy preoperative radiotherapy and to compare the results with a matched-control group of open TME ( OTME ) . Material s and methods A series of 41 patients with primary rectal cancer underwent LTME for rectal cancer and were matched with a historical control group of 41 patients who underwent OTME . Both groups received preoperative short-term radiotherapy . Results There was no mortality in the LTME group and 2 % mortality in the OTME group . The overall postoperative morbidity was 37 % in the LTME group and 51 % in the OTME group , including an anastomotic leakage of 9 and 14 % in the LTME and OTME groups respectively . A positive circumferential margin was found in 7 % of patients in the LTME group and in 12 % of the patients in the OTME group . Conclusion This study shows that LTME is technically feasible and can be performed safely . We show at least a similar surgical completeness using a laparoscopic technique compared with open surgery Objective To compare laparoscopic versus open surgery for rectal cancer and analyse the results of the multidisciplinary audited project on total mesorectal excision conducted in Spain . Background The safety and therapeutic efficiency of laparoscopic surgery for rectal cancer are controversial due to the technical difficulties it involves . A deviation from the oncological principles of mesorectal excision would mean a potential increase in local recurrence and shorter survival . Methods This prospect i ve non-r and omised multicentre study includes 4,970 patients with rectal cancer . The study compares perioperative , postoperative , anatomicopathological and survival variables . Results Five hundred and sixty five patients were excluded . Of the remaining 4,405 , 3,018 ( 68.51 % ) had open surgery ( OS ) and 1,387 ( 31.49 % ) laparoscopic surgery ( LS ) . The rate of anterior resections was higher in the LS group . The rate of intraoperative tumour perforation , number of red blood cell concentrates transfused and length of hospital stay were greater in the OS group , whereas surgical time was longer in the LS group . The incidence of complications was 45.6 % in the OS group and 38.3 % in the LS group . Involvement of the circumferential and distal margin , as well as unsatisfactory and partially satisfactory quality of the mesorectum , were greater in the OS group . There were no differences for local recurrence and survival rates . Conclusions According to these results , laparoscopic surgery is the best option for the surgical treatment of rectal cancer , with similar rates of local recurrence and survival , although there are oncological indicators in this study to suggest that these results can be improved with laparoscopic surgery BACKGROUND Although laparoscopic resection of colorectal carcinoma improves post-operative recovery , long-term survival and disease control are the determining factors for its application . We aim ed to test the null hypothesis that there was no difference in survival after laparoscopic and open resection for rectosigmoid cancer . METHODS From Sept 21 , 1993 , to Oct 21 , 2002 , 403 patients with rectosigmoid carcinoma were r and omised to receive either laparoscopic assisted ( n=203 ) or conventional open ( n=200 ) resection of the tumour . Survival and disease-free interval were the main endpoints . Patients were last followed-up in March , 2003 . Perioperative data were recorded and direct cost of operation estimated . Data were analysed by intention to treat . FINDINGS The demographic data of the two groups were similar . After curative resection , the probabilities of survival at 5 years of the laparoscopic and open resection groups were 76.1 % ( SE 3.7 % ) and 72.9 % ( 4.0 % ) respectively . The probabilities of being disease free at 5 years were 75.3 % ( 3.7 % ) and 78.3 % ( 3.7 % ) , respectively . The operative time of the laparoscopic group was significantly longer , whereas postoperative recovery was significantly better than for the open resection group , but these benefits were at the expense of higher direct cost . The distal margin , the number of lymph nodes found in the resected specimen , overall morbidity and operative mortality did not differ between groups . INTERPRETATION Laparoscopic resection of rectosigmoid carcinoma does not jeopardise survival and disease control of patients . The justification for adoption of laparoscopic technique would depend on the perceived value of its effectiveness in improving short-term post-operative outcomes Introduction The study compares the short-term results of the laparoscopic and open approach for the surgical treatment of rectal cancer . Consecutive cases with rectal cancer operated upon with laparoscopy from 2004 to 2007 were compared to open rectal cancer cases . Total mesorectal excision ( TME ) was attempted in all cases . Patients and methods Forty-two cases were included in the OPEN and 45 in the LAP group and were matched for age , gender , disease stage and operation type . Surgical procedure Duration of surgery was longer and blood transfusion requirements were less in the LAP group . Higher blood loss was observed in patients with neoadjuvant treatment in both groups . Patients with neoadjuvant treatment in the OPEN group had higher operation time , but that was not the case in the LAP group . There were three conversions ( 7 % ) . Results Overall morbidity was higher in the OPEN group . LAP group patients were found to recover faster . R0 resection was achieved in 88 % in the OPEN and 94 % in the LAP group . Discussion Less morbidity and faster recovery is offered after laparoscopic TME . Quality of surgery assessed by histopathology is similar between the approaches . Neoadjuvant chemoradiation seems to have significant impact on blood loss but results in longer operation times of the OPEN group Because definitive long-term results are not yet available , the oncologic safety of laparoscopic surgery in rectal cancer remains controversial . Laparoscopic total mesorectal excision ( LTME ) for rectal cancer has been proposed to have several short-term advantages in comparison with open total mesorectal excision ( OTME ) . However , few prospect i ve r and omized studies have been performed . The main purpose of our study was to evaluate whether relevant differences in safety and efficacy exist after elective LTME for the treatment of rectal cancer compared with OTME in a tertiary referral medical center . This comparative nonr and omized prospect i ve study analyzes data in 56 patients with middle and lower rectal cancer treated with low anterior resection or abdominoperineal resection from November 2005 to November 2007 . Follow-up was determined through office charts or direct patient contact . Statistical analysis was performed using χ2 test and Student 's t test . Twenty-eight patients underwent LTME and 28 patients were in the OTME group . No conversion was required in the LTME group . Mean operating time was shorter in the laparoscopic group ( LTME ) ( 181.3 vs 206.1 min , P < 0.002 ) . Less intraoperative blood loss and fewer postoperative complications were seen in the LTME group . Return of bowel motility was observed earlier after laparoscopic surgery . There was no 30-day mortality and the overall morbidity was 17 per cent in the LTME group versus 32 per cent in the OTME group . The mean number of harvested lymph nodes was greater in the laparoscopic group than in the OTME group ( 12.1 ± 2 vs 9.3 ± 3 ) . Mean follow-up time was 12 months ( range 9 - 24 months ) . No local recurrence was found . LTME is a feasible procedure with acceptable postoperative morbidity and low mortality , however it is technically dem and ing . This series confirms its safety , although oncologic results are at present comparable with the OTME published series with the limitation of a short follow-up period . Further r and omized studies are necessary to evaluate long-term clinical outcome BACKGROUND Historical data and recent studies show that st and ardised extended ( D2 ) lymphadenectomy leads to better results than st and ardised limited ( D1 ) lymphadenectomy . Based on these findings , the Dutch D1D2 trial , a nationwide prospect ively r and omised clinical trial , was undertaken to compare D2 with D1 lymphadenectomy in patients with resectable primary adenocarcinoma of the stomach . The aim of the study was to assess the effect of D2 compared with D1 surgery on disease recurrence and survival in patients treated with curative intent . METHODS Between August , 1989 , and July , 1993 , patients were entered and r and omised at 80 participating hospitals by means of a telephone call to the central data centre of the trial . The sequence of r and omisation was in blocks of six with stratification for the participating centre . Eligibility criteria were a histologically proven adenocarcinoma of the stomach without evidence of distance metastasis , age younger than 85 years , and adequate physical condition for D1 or D2 lymphadenectomy . Patients were excluded if they had previous or coexisting cancer or had undergone gastrectomy for benign tumours . Strict quality control measures for pathological assessment were implemented and monitored . Analyses were by intention to treat . This study is registered with the NCI trial register , as DUT-KWF-CKVO-8905 , EU-90003 . FINDINGS A total of 1078 patients were entered in the study , of whom 996 were eligible . 711 patients underwent the r and omly assigned treatment with curative intent ( 380 in the D1 group and 331 in the D2 group ) and 285 had palliative treatment . Data were collected prospect ively and all patients were followed up for a median time of 15.2 years ( range 6.9 - 17.9 years ) . Analyses were done for the 711 patients treated with curative intent and were according to the allocated treatment group . Of the 711 patients , 174 ( 25 % ) were alive , all but one without recurrence . Overall 15-year survival was 21 % ( 82 patients ) for the D1 group and 29 % ( 92 patients ) for the D2 group ( p=0.34 ) . Gastric-cancer-related death rate was significantly higher in the D1 group ( 48 % , 182 patients ) compared with the D2 group ( 37 % , 123 patients ) , whereas death due to other diseases was similar in both groups . Local recurrence was 22 % ( 82 patients ) in the D1 group versus 12 % ( 40 patients ) in D2 , and regional recurrence was 19 % ( 73 patients ) in D1 versus 13 % ( 43 patients ) in D2 . Patients who had the D2 procedure had a significantly higher operative mortality rate than those who had D1 ( n=32 [ 10 % ] vs n=15 [ 4 % ] ; 95 % CI for the difference 2 - 9 ; p=0.004 ) , higher complication rate ( n=142 [ 43 % ] vs n=94 [ 25 % ] ; 11 - 25 ; p<0.0001 ) , and higher reoperation rate ( n=59 [ 18 % ] vs n=30 [ 8 % ] ; 5 - 15 ; p=0.00016 ) . INTERPRETATION After a median follow-up of 15 years , D2 lymphadenectomy is associated with lower locoregional recurrence and gastric-cancer-related death rates than D1 surgery . The D2 procedure was also associated with significantly higher postoperative mortality , morbidity , and reoperation rates . Because a safer , spleen-preserving D2 resection technique is currently available in high-volume centres , D2 lymphadenectomy is the recommended surgical approach for patients with resectable ( curable ) gastric cancer . FUNDING Dutch Health Insurance Funds Council and The Netherl and s Cancer Foundation Background Only few studies have compared laparoscopic total mesorectal excision ( LTME ) and open total mesorectal excision ( OTME ) for rectal cancer with follow-up longer than 5 years . The aim of this study was to compare 10-year oncologic outcomes after LTME and OTME for nonmetastatic rectal cancer . Methods We conducted a retrospective analysis of a prospect i ve data base of rectal cancer patients undergoing LTME or OTME . Statistical analyses were performed on an ‘ ‘ intention-to-treat ’ ’ basis and by actual treatment . Overall survival ( OS ) and disease-free survival ( DFS ) were compared by using the Kaplan – Meier method . A multivariable analysis was performed to identify predictors of poor survival . Results Between April 1994 and August 2005 , a total of 153 LTME patients and 154 OTME patients were included . Similarly , 10-year OS and DFS after LTME and OTME were observed : 76.8 versus 70.6 % ( P = 0.138 ) and 69.1 versus 67.6 % ( P = 0.508 ) , respectively . Conversion to OTME did not adversely affect OS and DFS . Stage-by-stage comparison showed no significant differences between LTME and OTME . No significant differences were observed in local recurrence rates after LTME and OTME ( 6.5 vs. 7.8 % , P = 0.837 ) . Median time until local recurrence was 24.5 ( range , 12–56 ) months after LTME and 22 ( 6–64 ) months after OTME ( P = 0.777 ) . Poor tumor differentiation , lymphovascular invasion , and a lymph node ratio of 0.25 or more were the independent predictors of poorer OS and DFS . Conclusion This retrospective study with long follow-up did not show significant differences between the two groups in OS and DFS PURPOSE The aim of the current study is to report the long-term outcomes after laparoscopic-assisted surgery compared with conventional open surgery within the context of the UK MRC CLASICC trial . Results from r and omized trials have indicated that laparoscopic surgery for colon cancer is as effective as open surgery in the short term . Few data are available on rectal cancer , and long-term data on survival and recurrence are now required . METHODS The United Kingdom Medical Research Council Conventional versus Laparoscopic-Assisted Surgery in Colorectal Cancer ( UK MRC CLASICC ; clinical trials number IS RCT N 74883561 ) trial study comparing conventional versus laparoscopic-assisted surgery in patients with cancer of the colon and rectum . The r and omization ratio was 2:1 in favor of laparoscopic surgery . Long-term outcomes ( 3-year overall survival [ OS ] , disease-free survival [ DFS ] , local recurrence , and quality of life [ QoL ] ) have now been determined on an intention-to-treat basis . RESULTS Seven hundred ninety-four patients were recruited ( 526 laparoscopic and 268 open ) . Overall , there were no differences in the long-term outcomes . The differences in survival rates were OS of 1.8 % ( 95 % CI , -5.2 % to 8.8 % ; P = .55 ) , DFS of -1.4 % ( 95 % CI , -9.5 % to 6.7 % ; P = .70 ) , local recurrence of -0.8 % ( 95 % CI , -5.7 % to 4.2 % ; P = .76 ) , and QoL ( P > .01 for all scales ) . Higher positivity of the circumferential resection margin was reported after laparoscopic anterior resection ( AR ) , but it did not translate into an increased incidence of local recurrence . CONCLUSION Successful laparoscopic-assisted surgery for colon cancer is as effective as open surgery in terms of oncological outcomes and preservation of QoL. Long-term outcomes for patients with rectal cancer were similar in those undergoing abdominoperineal resection and AR , and support the continued use of laparoscopic surgery in these patients BACKGROUND : Laparoscopic resection for rectal cancer has remained controversial because of the lack of level 1 evidence regarding oncologic safety and long-term survival . OBJECTIVES : The aim of this study was to assess the impact of laparoscopic versus open resection for rectal cancer on clinical and oncologic outcome in the multimodal setting . DESIGN : This is a review of prospect ively gathered data from a single-institution rectal cancer data base . SETTING S : This study was conducted in the Central Hospital of Central Finl and . PATIENTS : From January 1999 to December 2006 , 191 selected patients were included . INTERVENTIONS : One hundred patients underwent laparoscopic resection , and 91 patients , also suitable for laparoscopic surgery , underwent open major rectal resection in the multimodal setting . MAIN OUTCOME MEASURES : The main measures of outcome were early recovery and short- and long-term morbidity ; local recurrence and survival were secondary outcomes . LIMITATIONS : This is not a r and omized study . RESULTS : The study groups were balanced for baseline characteristics . Conversion rate to open surgery was 22 % . Laparoscopic surgery result ed in significantly less bleeding ( 175 mL vs 500 mL , p < 0.001 ) , 1 day earlier recovery of normal diet ( 3 days vs 4 days , p = 0.001 ) , and shorter postoperative hospital stay ( 7 days vs 9 days , p < 0.001 ) . Postoperative 30-day mortality ( 1 % vs 3 % ) , morbidity ( 31 % vs 43 % ) , readmission ( 11 % vs 15 % ) , and reoperation ( 6 % vs 9 % ) rates were similar in the 2 groups , but significantly fewer patients in the laparoscopic group had long-term complications ( 19 % vs 36 % , p = 0.033 ) . The 5-year disease-free survival ( 78 % vs 80 % , p = 0.74 ) and local recurrence ( 5 % vs 6 % , p = 0.66 ) rates were similar in the laparoscopic and open group for those 175 patients treated for cure . CONCLUSION : Laparoscopic surgery result ed in faster postoperative recovery and fewer long-term complications than open surgery without apparently compromising the long-term oncologic outcome . Our results indicate that laparoscopic rectal resection is an acceptable alternative to open surgery in selected patients with rectal cancer AIM To investigate the short-term outcome of laparoscopic total mesorectal excision ( TME ) in patients with mid and low rectal cancers . METHODS A consecutive series of 138 patients with middle and low rectal cancer were r and omly assigned to either the laparoscopic TME ( LTME ) group or the open TME ( OTME ) group between September 2008 and July 2011 at the Department of Colorectal Cancer of Shanghai Cancer Center , Fudan University and pathological data , as well as surgical technique were review ed retrospectively . Short-term clinical and oncological outcome were compared in these two groups . Patients were followed in the outpatient clinic 2 wk after the surgery and then every 3 mo in the first year if no adjuvant chemoradiation was indicated . Statistical analysis was performed using SPSS 13.0 software . RESULTS Sixty-seven patients were treated with LTME and 71 patients were treated with OTME ( sex ratio 1.3:1 vs 1.29:1 , age 58.4 ± 13.6 years vs 59.6 ± 9.4 years , respectively ) . The resection was considered curative in all cases . The sphincter-preserving rate was 65.7 % ( 44/67 ) vs 60.6 % ( 43/71 ) , P = 0.046 ; mean blood loss was 86.9 ± 37.6 mL vs 119.1 ± 32.7 mL , P = 0.018 ; postoperative analgesia was 2.1 ± 0.6 d vs 3.9 ± 1.8 d , P = 0.008 ; duration of urinary drainage was 4.7 ± 1.8 d vs 6.9 ± 3.4 d , P = 0.016 , respectively . The conversion rate was 2.99 % . The complication rate , circumferential margin involvement , distal margins and lymph node yield were similar for both procedures . No port site recurrence , anastomotic recurrence or mortality was observed during a median follow-up period of 21 mo ( range : 9 - 56 mo ) . CONCLUSION Laparoscopic TME is safe and feasible , with an oncological adequacy comparable to the open approach . Further studies with more patients and longer follow-up are needed to confirm the present results BACKGROUND Laparoscopic total mesorectal excision ( TME ) is being used in rectal cancer more frequently . The aim of this study was to analyze the differences in short-term outcomes between open and laparoscopic TME . METHODS In this nonr and omized consecutive study , the short-term outcomes of 100 patients undergoing TME for proven rectal cancer were analyzed . RESULTS Two groups of 50 patients underwent an open or laparoscopic TME for rectal cancer . Both groups were comparable . Laparoscopic surgery took longer to perform ( 250 vs. 197.5 min , p < 0.01 ) , but was accompanied by less blood loss ( 350 vs. 800 ml , p < 0.01 ) . Enteric function recovered sooner after laparoscopy . The numbers of major and minor complications were comparable between both groups , although fewer patients had major complications in the laparoscopic group ( 6 vs. 15 patients , p = 0.03 ) . Hospital stay was shorter for patients who underwent a laparoscopic abdominoperineal resection ( 10 vs. 12 days , p = 0.04 ) . Median follow-up was 17 months for the laparoscopic group and 22 months for the open group . Survival analyses between the groups showed no statistical difference in disease-free and overall survival . CONCLUSION This study shows that laparoscopic TME for rectal cancer is a safe and feasible technique with some short-term benefits over open TME Abstract PURPOSE : This study was conducted to investigate the feasibility of laparoscopic resection of rectal cancer and to compare early outcome data with the results of the conventional technique . METHODS : From January 1996 to March 2002 , 435 patients with primary rectal cancer were operated on at our institution . Low-risk , small rectal tumors treatable by local excision , rectal cancer recurrences , and emergency cases were excluded from the analysis . Three hundred thirty-four patients were operated on by the conventional open approach . One hundred one selected patients underwent surgery by the laparoscopic technique . RESULTS : Because of the selection process , significantly more patients with early tumor stages were operated on by laparoscopy . There were no differences in mean operation time , morbidity , mortality , or the anastomotic leakage rate ; however , the need for intraoperative transfusion , mean stay in the intensive care unit , and length of hospital stay were reduced significantly . CONCLUSIONS : In terms of the intraoperative and early postoperative course , the laparoscopic resection of rectal cancer in a selected cohort of patients compares favorably with the open technique . Because follow- up time is limited to date , only very preliminary information can be given on tumor-related outcome data . However , these preliminary data appear to suggest that rectal cancer resection can be performed by laparoscopy in accordance with established principles of cancer therapy and that port-site metastases are not a relevant clinical problem . Prospect i ve , r and omized trials are required to determine whether the laparoscopic approach will play a significant role in the treatment of rectal cancer in the future BACKGROUND : Evidence demonstrates short-term benefits of laparoscopic surgery for colon cancer . The situation for rectal cancer is less clear . OBJECTIVES : This review assessed the use and short-term outcomes of elective open and laparoscopic colon and rectal cancer resections within an area health service . DESIGN : This was a multicenter , retrospective review of a prospect i ve data base . SETTING S : All elective colon and rectal cancer resections in the western zone of Sydney South West Area Health Service from 2001 until 2008 were included . PATIENTS : Included were 1721 patients who underwent either a laparoscopic colon ( n = 434 ) or rectal ( n = 157 ) resection or an open colon ( n = 742 ) or rectal ( n = 388 ) resection . MAIN OUTCOME MEASURES : Outcome measures included operating time , blood loss , adequacy of resection , conversion rate , intensive care unit admission , length of stay , and 26 acute postoperative complications . RESULTS : Patients were matched for age , sex , ASA , BMI , and tumor stage . Laparoscopic surgery increased in frequency . Fewer patients experienced a complication in both the laparoscopic colon ( 28.8 vs 54.4 % ; p < 0.0001 ) and rectal ( 41.4 vs 60.3 % ; p < 0.0001 ) group irrespective of age . Laparoscopic operating time for colon and rectal cancer was 24.1 minutes ( p < 0.0001 ) and 25.8 minutes ( p < 0.0001 ) longer , with a low conversion-to-open rate ( 6.5 % and 8.3 % ; p = 0.44 ) . Laparoscopic surgery result ed in fewer transfusions ( 0.4 vs 0.7units ; p = 0.0028 ) and length of stay ( 7 vs 10 days ; p = 0.0011 ) for colon cancers , and reduced intraoperative hemoglobin drop ( 20.5 vs 24.8 ; p = 0.029 ) and intensive care unit admissions ( 26.8 vs 36.3 % ; p = 0.032 ) for rectal cancers . LIMITATIONS : This was a nonr and omized study with rectal cancers more often resected with the open technique ( 71.2 vs 28.8 % ; p < 0.001 ) . CONCLUSIONS : Within an area health service , elective laparoscopic resection for colon and rectal cancer had improved short-term outcomes in comparison with open surgery Background This single-center , prospect i ve , r and omized trial was design ed to compare the short-term clinical outcome between laparoscopic-assisted versus open total mesorectal excision ( TME ) with anal sphincter preservation ( ASP ) in patients with mid and low rectal cancer . Long-term morbidity and survival data also were recorded and compared between the two groups . Methods Between August 2001 and August 2007 , 80 patients with mid and low rectal cancer were r and omized to receive either laparoscopic-assisted ( 40 patients ) or open ( 40 patients ) TME with ASP . The median follow-up time for all patients was 75.7 ( range 16.9–115.7 ) months for the laparoscopic-assisted group and 76.1 ( range 4.7–126.6 ) months for the open group . The primary endpoint of the study was short-term clinical outcome . Secondary endpoints included long-term morbidity rate and survival . Data were analyzed by intention-to-treat principle . Results The demographic data of the two groups were comparable . Postoperative recovery was better after laparoscopic surgery , with less analgesic requirement ( P < 0.001 ) , earlier mobilization ( P = 0.001 ) , lower short-term morbidity rate ( P = 0.043 ) , and a trend towards shorter hospital stay ( P = 0.071 ) . The cumulative long-term morbidity rate also was lower in the laparoscopic-assisted group ( P = 0.019 ) . The oncologic clearance in terms of macroscopic quality of the TME specimen , circumferential resection margin involvement , and number of lymph nodes removed was similar between both groups . After curative resection , the probabilities of survival at 5 years of the laparoscopic-assisted and open groups were 85.9 and 91.3 % , respectively ( P = 0.912 ) . The respective probabilities of being disease-free were 83.3 and 74.5 % ( P = 0.114 ) . Conclusions Laparoscopic-assisted TME with ASP improves postoperative recovery , reduces short-term and long-term morbidity rates , and seemingly does not jeopardize survival compared with open surgery for mid and low rectal cancer ( http:// Clinical Trials.gov Identifier : NCT00485316 ) Background : Controversy continues to surround laparoscopic rectal resection for malignancy . A longer follow-up period is required to evaluate the long-term efficacy of the procedure and its impact on survival . Furthermore , no data from ongoing r and omized controlled trials are yet available . The aims of this study were to compare long-term outcomes for unselected patients undergoing either laparoscopic or open rectal resection for cancer . Methods : A series of 124 unselected consecutive patients with rectal cancer , who underwent surgery by the same surgical team , have been included in this study . Patients with T1N0 tumors underwent local excision , and emergency cases were excluded from the study . Written consent was su bmi tted by each patient , and inclusion in either group ( laparoscopic or open ) was left to the patient ’s choice . The laparoscopic approach was chosen by 81 patients , and 43 patients chose open surgery . All the patients underwent preoperative radiotherapy ( 5,040 cGy ) , performed in selected cases with chemotherapy ( for patients younger than 70 years ) . The following parameters were compared between the two groups : length of the surgical specimen , clearance of the margins of the specimen , number of lymph nodes identified , local recurrence rate , incidence of distant metastases , and survival probability analysis . The mean follow-up period for both groups was 43.8 months ( range , l–9 years ) . Results : We performed 60 laparoscopic and 27 open anterior resections , as well as 21 laparoscopic and 16 open abdomino perineal resections , respectively . No mortality occurred in either group . The mean length of the resected specimens was 24.3 cm in the laparoscopic group and 23.8 cm in the open group ( p = 0.47 ) . The mean tumor-free margin was 3.0 cm in the laparoscopic group and 2.8 cm in the open group ( p = 0.57 ) , and the mean number of lymph nodes identified was 10.3 in the laparoscopic group and 9.8 in the open group ( p = 0.63 ) . Of the 124 patients , 86 ( 52 laparoscopic and 34 open ) were included in out study . We excluded patients who underwent a palliative resection ( 6 laparoscopic and 6 open patients ) or conversion to open surgery ( n = 10 ) and patients who had undergone surgery in the past year ( n = 16 ) . One laparoscopic patient was lost to follow-up evaluation , whereas three laparoscopic patients and one open patient died of causes not related to cancer . No wound recurrence was observed . The local recurrence rate after laparoscopic resection was 20.8 % , as compared with 16.6 % after open resection ( p = 0.687 ) . Distant metastases occurred in 18.2 % of the patients in the laparoscopic group , as compared with 21.2 % in the open group ( p = 0.528 ) . Cumulative survival probability was 0.709 after laparoscopic resection after LR and 0.606 after open resection ( p = 0.162 ) , whereas for Dukes ’ stages A , B , and C in the laparoscopic group versus the open group , it was 0.875 vs 0.889 ( p = 0.392 ) , 0.722 vs 0.584 ( p = 0.199 ) , and 0.500 vs 0.417 ( p = 0.320 ) , respectively . At this writing 20 laparoscopic patients ( 62.5 % ) and 20 open patients ( 60.6 % ) are disease free ( p = 0.623 ) . Conclusions : Oncologic surgical principles were respected . Long-term outcome after laparoscopic resection of rectal cancer was comparable with that after conventional resection . We should wait to draw conclusive scientific statements until the completion of ongoing international radomized controlled trials BACKGROUND The safety and short-term efficacy of laparoscopic surgery for rectal cancer after preoperative chemoradiotherapy has not been demonstrated . The aim of the r and omised Comparison of Open versus laparoscopic surgery for mid and low REctal cancer After Neoadjuvant chemoradiotherapy ( COREAN ) trial was to compare open surgery with laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy . METHODS Between April 4 , 2006 , and Aug 26 , 2009 , patients with cT3N0 - 2 mid or low rectal cancer without distant metastasis after preoperative chemoradiotherapy were enrolled at three tertiary-referral hospitals . Patients were r and omised 1:1 to receive either open surgery ( n=170 ) or laparoscopic surgery ( n=170 ) , stratified according to sex and preoperative chemotherapy regimen . Short-term outcomes assessed were involvement of the circumferential resection margin , macroscopic quality of the total mesorectal excision specimen , number of harvested lymph nodes , recovery of bowel function , perioperative morbidity , postoperative pain , and quality of life . Analyses were based on the intention-to-treat population . Patients continue to be followed up for the primary outcome ( 3-year disease-free survival ) . This study is registered with Clinical Trials.gov , number NCT00470951 . FINDINGS Two patients ( 1.2 % ) in the laparoscopic group were converted to open surgery , but were included in the laparoscopic group for analyses . Estimated blood loss was less in the laparoscopic group than in the open group ( median 217.5 mL [ 150.0 - 400.0 ] in the open group vs 200.0 mL [ 100.0 - 300.0 ] in the laparoscopic group , p=0.006 ) , although surgery time was longer in the laparoscopic group ( mean 244.9 min [ SD 75.4 ] vs 197.0 min [ 62.9 ] , p<0.0001 ) . Involvement of the circumferential resection margin , macroscopic quality of the total mesorectal excision specimen , number of harvested lymph nodes , and perioperative morbidity did not differ between the two groups . The laparoscopic surgery group showed earlier recovery of bowel function than the open surgery group ( time to pass first flatus , median 38.5 h [ 23.0 - 53.0 ] vs 60.0 h [ 43.0 - 73.0 ] , p<0.0001 ; time to resume a normal diet , 85.0 h [ 66.0 - 95.0 ] vs 93.0 h [ 86.0 - 121.0 ] , p<0.0001 ; time to first defecation , 96.5 h [ 70.0 - 125.0 ] vs 123 h [ 94.0 - 156.0 ] , p<0.0001 ) . The total amount of morphine used was less in the laparoscopic group than in the open group ( median 107.2 mg [ 80.0 - 150.0 ] vs 156.9 mg [ 117.0 - 185.2 ] , p<0.0001 ) . 3 months after proctectomy or ileostomy takedown , the laparoscopic group showed better physical functioning score than the open group ( 0.501 [ n=122 ] vs -4.970 [ n=128 ] , p=0.0073 ) , less fatigue ( -5.659 [ n=122 ] vs 0.098 [ n=129 ] , p=0.0206 ) , and fewer micturition ( -2.583 [ n=122 ] vs 4.725 [ n=129 ] , p=0.0002 ) , gastrointestinal ( -0.400 [ n=122 ] vs 4.331 [ n=129 ] , p=0.0102 ) , and defecation problems ( 0.535 [ n=103 ] vs 5.327 [ n=99 ] , p=0.0184 ) in repeated measures analysis of covariance , adjusted for baseline values . INTERPRETATION Laparoscopic surgery after preoperative chemoradiotherapy for mid or low rectal cancer is safe and has short-term benefits compared with open surgery ; the quality of oncological resection was equivalent BACKGROUND The long-term survival and safety of laparoscopic surgery in patients with rectal cancer remain unclear . The aim of this trial was to assess the efficacy and safety of laparoscopic surgery for treatment of rectal cancer . METHODS We undertook a r and omized , controlled trial in 343 patients with rectal cancer between May 2004 and April 2008 . One hundred sixty-nine patients were r and omly assigned to laparoscopic surgery and 174 patients to open surgery . The main endpoint was 3-year survival . Data were analyzed according to the intention-to-treat principle . RESULTS Laparoscopic surgery was associated with earlier recovery of bowel movement compared with open surgery . The average time to first discharge , bowel movement , resumption of fluid intake , and activity out of bed in laparoscopic surgery were shorter by 0.63 , 0.32 , 0.33 , and 0.63 day , respectively ( P < .001 ) . The incidences of postoperative morbidities such as infectious complications , anastomotic leakage , anastomotic stenosis , and deep vein thrombosis have no differences . No differences were found in the comparison of long-term survival . INTERPRETATION Laparoscopic surgery for rectal cancer is as safe and effective as open surgery in terms of oncology outcomes . Long-term survival for patients with rectal cancer undergoing laparoscopic surgery were similar to those undergoing conventional open surgery , thus supporting the continued use of laparoscopic surgery in Chinese patients with rectal cancer IMPORTANCE Laparoscopic procedures are generally thought to have better outcomes than open procedures . Because of anatomical constraints , laparoscopic rectal resection may not be better because of limitations in performing an adequate cancer resection . OBJECTIVE To determine whether laparoscopic resection is noninferior to open rectal cancer resection for adequacy of cancer clearance . DESIGN , SETTING , AND PARTICIPANTS R and omized , noninferiority , phase 3 trial ( Australasian Laparoscopic Cancer of the Rectum ; ALaCaRT ) conducted between March 2010 and November 2014 . Twenty-six accredited surgeons from 24 sites in Australia and New Zeal and r and omized 475 patients with T1-T3 rectal adenocarcinoma less than 15 cm from the anal verge . INTERVENTIONS Open laparotomy and rectal resection ( n = 237 ) or laparoscopic rectal resection ( n = 238 ) . MAIN OUTCOMES AND MEASURES The primary end point was a composite of oncological factors indicating an adequate surgical resection , with a noninferiority boundary of Δ = -8 % . Successful resection was defined as meeting all the following criteria : ( 1 ) complete total mesorectal excision , ( 2 ) a clear circumferential margin ( ≥1 mm ) , and ( 3 ) a clear distal resection margin ( ≥1 mm ) . Pathologists used st and ardized reporting and were blinded to the method of surgery . RESULTS A successful resection was achieved in 194 patients ( 82 % ) in the laparoscopic surgery group and 208 patients ( 89 % ) in the open surgery group ( risk difference of -7.0 % [ 95 % CI , -12.4 % to ∞ ] ; P = .38 for noninferiority ) . The circumferential resection margin was clear in 222 patients ( 93 % ) in the laparoscopic surgery group and in 228 patients ( 97 % ) in the open surgery group ( risk difference of -3.7 % [ 95 % CI , -7.6 % to 0.1 % ] ; P = .06 ) , the distal margin was clear in 236 patients ( 99 % ) in the laparoscopic surgery group and in 234 patients ( 99 % ) in the open surgery group ( risk difference of -0.4 % [ 95 % CI , -1.8 % to 1.0 % ] ; P = .67 ) , and total mesorectal excision was complete in 206 patients ( 87 % ) in the laparoscopic surgery group and 216 patients ( 92 % ) in the open surgery group ( risk difference of -5.4 % [ 95 % CI , -10.9 % to 0.2 % ] ; P = .06 ) . The conversion rate from laparoscopic to open surgery was 9 % . CONCLUSIONS AND RELEVANCE Among patients with T1-T3 rectal tumors , noninferiority of laparoscopic surgery compared with open surgery for successful resection was not established . Although the overall quality of surgery was high , these findings do not provide sufficient evidence for the routine use of laparoscopic surgery . Longer follow-up of recurrence and survival is currently being acquired . TRIAL REGISTRATION anzctr.org Identifier : ACTRN12609000663257 BACKGROUND Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale r and omised trials to support its use . We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes . METHODS Between July , 1996 , and July , 2002 , we undertook a multicentre , r and omised clinical trial in 794 patients with colorectal cancer from 27 UK centres . Patients were allocated to receive laparoscopic-assisted ( n=526 ) or open surgery ( n=268 ) . Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins , proportion of Dukes ' C2 tumours , and in-hospital mortality . Analysis was by intention to treat . This trial has been assigned the International St and ard R and omised Controlled Trial Number IS RCT N74883561 . FINDINGS Six patients ( two [ open ] , four [ laparoscopic ] ) had no surgery , and 23 had missing surgical data ( nine , 14 ) . 253 and 484 patients actually received open and laparoscopic-assisted treatment , respectively . 143 ( 29 % ) patients underwent conversion from laparoscopic to open surgery . Proportion of Dukes ' C2 tumours did not differ between treatments ( 18 [ 7 % ] patients , open vs 34 [ 6 % ] , laparoscopic ; difference -0.3 % , 95 % CI -3.9 to 3.4 % , p=0.89 ) , and neither did in-hospital mortality ( 13 [ 5 % ] vs 21 [ 4 % ] ; -0.9 % , -3.9 to 2.2 % , p=0.57 ) . Apart from patients undergoing laparoscopic anterior resection for rectal cancer , rates of positive resection margins were similar between treatment groups . Patients with converted treatment had raised complication rates . INTERPRETATION Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes . However , impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use |
2,243 | 22,336,841 | Current evidence is insufficient to support Pycnogenol ( ® ) use for the treatment of any chronic disorder . | BACKGROUND Oxidative stress has been implicated in the development of a number of conditions including cancer , arthritic disorders and cardiovascular disease .
Pycnogenol ( ® ) , a herbal dietary supplement derived from French maritime pine bark extract , is st and ardised to contain 70 % procyanidin which is a powerful antioxidant .
Pycnogenol ( ® ) is marketed as a supplement for preventing or treating a wide range of chronic conditions .
OBJECTIVES To assess the efficacy and safety of Pycnogenol ( ® ) for the treatment of chronic disorders . | 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 The aim of this study was to investigate the clinical efficacy of oral Pycnogenol ® ( Horphag Research Ltd , UK ) in patients with severe chronic venous insufficiency . Patients with severe venous hypertension ( chronic venous insufficiency , ankle swelling ) and history of venous ulcerations were treated with Pycnogenol . Patients received oral Pycnogenol ( 50 mg capsules , 3 times daily for a total of 150 mg daily ) for 8 weeks . A group of 21 patients was included in the treatment group and 18 equivalent patients were observed as controls ( no treatment during the observation period ) . All 21 patients ( age 53 years ; range , 42 - 60 years ; M : F=11:10 ) in the treatment group completed the 8-week study . Also the 18 controls completed the follow-up period . There were no drop-outs . The average ambulatory venous pressure was 59.3 ( SD 7.2 ; range 50 - 68 ) with a refilling time shorter than 10 seconds ( average 7.6 ; SD 3 ) . There were no differences in ambulatory venous pressure or refilling time between the treatment and control patients . The duration of the disease — from the first signs/symptoms — was on average 5.7 years ( SD 2.1 ) . At 4 and 8 weeks , in all Pycnogenol-treated subjects , microcirculatory and clinical evaluations indicated a progressive decrease in skin flux , indicating an improvement in the level of microangiopathy ; a significant decrease in capillary filtration ; a significant improvement in the symptomatic score ; and a reduction in edema . There were no visible effects in controls . In conclusion , this study confirms the fast clinical efficacy of Pycnogenol in patients with chronic venous insufficiency and venous microangiopathy . The study indicates the significant clinical role of Pycnogenol in the management , treatment and control of this common clinical problem . The treatment may be also useful to prevent ulcerations by controlling the level of venous microangiopathy The purpose of this r and omized , double-blind and placebo controlled study was to test the effect of polyphenolic extract of pine bark Pycnogenol ® ( Pyc ) on the level of oxidized purines represented by 8-oxo-7,8-dihydroguanine ( 8-oxoG ) and on the total antioxidant status ( TAS ) in children with attention deficit/hyperactivity disorder ( ADHD ) . We have found significantly increased damage to DNA in ADHD children when compared to controls . 8-oxoG was significantly lower after 1 month of Pyc administration in comparison to the beginning state and to placebo group . TAS in ADHD children was lower in comparison to controls . After Pyc administration , TAS was elevated but statistically significant increase was recorded after 1 month of termination of Pyc application . Improvement of DNA damage and TAS after Pyc administration is associated with the improvement of attention in ADHD children . In conclusion , Pycnogenol ® administration reduces oxidative damage to DNA , normalizes TAS and improves attention of ADHD children . Explanation of mutual relation between oxidative damage to DNA , TAS and symptoms of ADHD and mechanism of Pyc 's action needs further investigations Melasma ( or chloasma ) is a common disorder of cutaneous hyperpigmentation predominantly affecting sun-exposed areas in women . The pathogenesis of melasma is not fully understood and treatments are frequently disappointing and often associated with side effects . Pycnogenol is a st and ardized extract of the bark of the French maritime pine ( Pinus pinaster ) , a well-known , potent antioxidant . Studies in vitro show that Pycnogenol is several times more powerful than vitamin E and vitamin C. In addition , it recycles vitamin C , regenerates vitamin E and increases the endogenous antioxidant enzyme system . Pycnogenol protects against ultraviolet ( UV ) radiation . Therefore its efficacy in the treatment of melasma was investigated . Thirty women with melasma completed a 30-day clinical trial in which they took one 25 mg tablet of Pycnogenol with meals three times daily , i.e. 75 mg Pycnogenol per day . These patients were evaluated clinical ly by parameters such as the melasma area index , pigmentary intensity index and by routine blood and urine tests . After a 30-day treatment , the average melasma area of the patients decreased by 25.86 + /- 20.39 mm(2 ) ( p < 0.001 ) and the average pigmentary intensity decreased by 0.47 + /- 0.51 unit ( p < 0.001 ) . The general effective rate was 80 % . No side effect was observed . The results of the blood and urine test parameters at baseline and at day 30 were within the normal range . Moreover , several other associated symptoms such as fatigue , constipation , pains in the body and anxiety were also improved . To conclude , Pycnogenol was shown to be therapeutically effective and safe in patients suffering from melasma Asthma is characterized as a chronic inflammatory process . Pycnogenol((R ) ) , a bioflavonoid mixture extracted from Pinus maritima , is known to scavenge free radicals while possessing antioxidant and antiinflammatory properties . The objective of this study was to evaluate the efficiency of this agent in a r and omized , double-blinded , placebo-controlled , crossover study in patients with varying asthma severity . Twenty-six patients who fulfilled the American Thoracic Society criteria for asthma were enrolled in the study . Medical history , physical examination , blood sample analyses , and spirometric values were obtained at baseline , 4 weeks , and 8 weeks . The patients were r and omly assigned to receive either 1 mg/lb/day ( maximum 200 mg/day ) Pycnogenol or placebo for the first period of 4 weeks and then crossed over to the alternate regimen for the next 4 weeks . No adverse effects were observed related to the study drug . Within the contingent of 22 patients who completed the study , almost all responded favorably to Pycnogenol in contrast to placebo . Pycnogenol treatment also significantly reduced serum leukotrienes compared with placebo . The results of this pilot study indicate that Pycnogenol may be a valuable nutraceutical in the management of chronic asthma . We recommend that further clinical trials be conducted in larger groups of asthmatics to establish its efficacy The aim of this study was to compare the efficacy of Venostasin ( horse chestnut seed extract ) and Pycnogenol ( French maritime pine bark extract ) in the treatment of chronic venous insufficiency ( CVI ) . In an open , controlled comparative study 40 patients with diagnosed CVI were treated either with 600 mg chestnut seed extract per day or 360 mg Pycnogenol per day over a period of 4 weeks . The following parameters were investigated before the start of treatment and after 2 and 4 weeks of treatment : circumference of the lower legs and rating of subjective symptoms ( scores ) of pain , cramps , night-time swelling , feeling of " heaviness " , and reddening of the skin . In addition , blood levels of cholesterol LDL and HDL were determined before and at the end of treatment . Pycnogenol significantly reduced the circumference of the lower limbs and significantly improved subjective symptoms . Furthermore , Pycnogenol significantly decreased cholesterol and LDL values in the blood , whereas HDL remained unaffected . Venostasin only moderately but not significantly , reduced the circumference of the lower limbs and marginally improved symptoms . Venostasin had no influence on the determined lipid values . Both medications were equally well tolerated . In conclusion , Pycnogenol was found to be more efficacious than Venostasin for the treatment of CVI The aim of this study was to investigate the clinical efficacy of oral Pycnogenol ® ( Horphag Research Ltd , United Kingdom ) in patients with diabetic microangiopathy . Patients without a history of diabetic ulcerations were treated with Pycnogenol . Patients received oral Pycnogenol ( 50 mg capsules , 3 times daily for a total of 150 mg daily for 4 weeks ) . A group of 30 patients was included ( severe microangiopathy ) ; 30 comparable patients were observed as controls ( no treatment during the observation period ) . All patients ( age , 59 years ; range , 55 - 68 years ; male : female = 18:12 ) included in the treatment group completed the 4-week study . Also , all controls completed the follow-up period . There were no drop-outs . All included subjects had signs and symptoms of diabetic microangiopathy . The duration of diabetes — from the first signs/symptoms — was on average 7.5 years ( SD = 3 ) . After 4 weeks , microcirculatory and clinical evaluations showed a progressive decrease in skin flux at rest in the foot ( indicating an improvement in the level of microangiopathy ) , a significant decrease in capillary filtration , and a significant improvement in the venoarteriolar response in all treated subjects . There were no visible effects in controls except a slight reduction in skin flux at rest in the foot . Treatment was well tolerated in both groups . In conclusion , this study confirms the clinical efficacy of Pycnogenol in patients with diabetic microangiopathy . The study indicates the clinical role of Pycnogenol in the management , treatment , and control of this common clinical problem . The treatment may be also useful to prevent diabetic ulcerations by controlling the level of microangiopathy OBJECTIVE The safe and efficacious use of Pycnogenol ( French maritime pine bark extract ) in other inflammatory diseases prompted this study of its antiinflammatory effects in patients with osteoarthritis ( OA ) . The aim of the study was to evaluate whether Pycnogenol reduces the symptoms of OA in a double-blind , placebo-controlled , r and omly allocated trial with patients suffering from knee osteoarthritis stages I and II . METHODS 100 patients were treated for 3 months either by 150 mg Pycnogenol per day at meals or by placebo . Patients had to report any change of use of previously prescribed antiinflammatory medication during the study period . Patients filled the Western Ontario and Mc Masters University ( WOMAC ) question naire for osteoarthritis every 2 weeks and evaluated weekly pain symptoms using a visual analogue scale for pain intensity . RESULTS Following treatment with Pycnogenol patients reported an improvement of WOMAC index ( p < 0.05 ) , and a significant alleviation of pain by visual analogue scale ( p < 0.04 ) , the placebo had no effect . The use of analgesics diminished in the verum group but increased under the placebo . Treatment with Pycnogenol was well tolerated . CONCLUSION Results show that Pycnogenol in patients with mild to moderate OA improves symptoms and is able to spare NSAIDs Patients with type 2 diabetes are at considerable risk of excessive morbidity and mortality from cardiovascular disease ( CVD ) . We investigated the clinical effectiveness of Pycnogenol , a flavonoid-rich dietary supplement , in reducing antihypertensive medication use and CVD risk factors in subjects with type 2 diabetes . Forty-eight individuals were enrolled in a r and omized , double-blind , placebo-controlled trial with parallel-group design . Patients were diagnosed with both type 2 diabetes and mild to moderate hypertension and were undergoing treatment with angiotensin-converting enzyme ( ACE ) inhibitors . Subjects were r and omly assigned to receive either Pycnogenol pill ( 125 mg daily ) or matched placebo for 12 weeks . According to the values of blood pressure ( BP ) measured at 2-week intervals , the pretrial ACE inhibitor dosage was left unchanged , reduced by 50 % , or brought back to the pretrial dosage until a stable BP was obtained . Fasting plasma glucose , low-density lipoprotein ( LDL ) cholesterol , glycosylated hemoglobin ( HbA1c ) , serum endothelin-1 , and urinary albumin were evaluated monthly . Pycnogenol treatment achieved BP control in 58.3 % of subjects at the end of the 12 weeks with 50 % reduction in individual pretrial dose of ACE-inhibitors ( P < .05 ) . Plasma endothelin-1 decreased by 3.9 pg/mL in Pycnogenol-treated group vs 0.5 pg/mL increase in control group ( P < .001 ) . Mean HbA1c dropped by 0.8 % in Pycnogenol-treated group ( P < .05 ) , whereas it decreased by 0.1 % in control group . Fasting plasma glucose declined by 23.7 mg/dL in Pycnogenol-treated group vs 5.7 mg/dL in control group ( P < .0001 ) . Low-density lipoprotein cholesterol improved significantly in Pycnogenol-treated group , declining by 12.7 mg/dL ( P < .001 ) . A significant decrease in urinary albumin level was observed at week 8 compared with the control group ( P < .05 ) . However , this reduction was not significant at 12th week . After 12 weeks of supplementation , Pycnogenol result ed in improved diabetes control , lowered CVD risk factors , and reduced antihypertensive medicine use vs controls The aim of out study was to investigate the efficacy of Pycnogenol - a French maritime pine bark extract - in the treatment of chronic venous insufficiency ( CVI ) . The study consisted of a double-blind phase - in which 20 patients were recruited and r and omly treated with placebo or Pycnogenol ( 100 mg 2 3/day for 2 months ) - and an open phase - in which other 20 patients were treated with Pycnogenol at the same dose schedule . In total , 40 patients were enrolled ; 30 of them were treated with Pycnogenol and 10 with placebo . Pycnogenol significantly improved the legs ' heaviness and subcutaneous edema ; the venous pressure was also significantly reduced by the Pycnogenol treatment , thus adding further clinical evidence to its therapeutic efficacy in patients with CVI . Pycnogenol was effective , probably by either stabilizing the collagenous subendothelial basal membrane or scavenging the free radicals , or by a combination of these activities . Clinical ly , capillary leakage , perivascular inflammation and subcutaneous edema were all reduced . The safety of use of Pycnogenol is demonstrated by the lack of side effects or changes in blood biochemistry and hematologic parameters . Pycnogenol can be therefore recommended both for prevention and treatment of CVI and related veno-capillary disturbances A placebo-controlled , double-blind , parallel group study was performed with 58 patients to investigate effects of French maritime pine bark extract , Pycnogenol , on patients with hypertension . Supplementation of the patients with 100 mg Pycnogenol over a period of 12 weeks helped to reduce the dose of the calcium antagonist nifedipine in a statistically significant manner . The intake of Pycnogenol decreased endothelin-1 concentrations significantly compared to placebo while concentrations of 6-keto prostagl and in F1a in plasma were significantly higher compared to placebo . Values for nitric oxide ( NO ) in plasma increased in both groups , but the differences were not significant . Angiotensin II concentrations in plasma were lowered in the placebo group to a larger extent than in the Pycnogenol group . Heart rate , electrolytes and blood urea nitrogen were not changed during treatment in both groups of patients . Unwanted effects observed in both groups were of mild and transient nature , such as gastrointestinal problems , vertigo , headache and nausea . Differences in rate of side effects were not statistically significant between the two groups . Study results support a supplementation with Pycnogenol for mildly hypertensive patients A r and omized , placebo‐controlled , double‐blind study involving 60 subjects , aged 6–18 years old , was conducted over a period of 3 months to determine the effect of Pycnogenol ® ( a proprietary mixture of water‐soluble bioflavonoids extracted from French maritime pine ) on mild‐to‐moderate asthma . After baseline evaluation , subjects were r and omized into two groups to receive either Pycnogenol ® or placebo . Subjects were instructed to record their peak expiratory flow with an Assess ® Peak Flow Meter each evening . At the same time , symptoms , daily use of rescue inhalers ( albuterol ) , and any changes in oral medications were also recorded . Urine sample s were obtained from the subjects at the end of the run‐in period , and at 1‐ , 2‐ , and 3‐month visits . Urinary leukotriene C4/D4/E4 was measured by an enzyme immunoassay . Compared with subjects taking placebo , the group who took Pycnogenol ® had significantly more improvement in pulmonary functions and asthma symptoms . The Pycnogenol ® group was able to reduce or discontinue their use of rescue inhalers more often than the placebo group . There was also a significant reduction of urinary leukotrienes in the Pycnogenol ® group . The results of this study demonstrate the efficacy of Pycnogenol ® as an adjunct in the management of mild‐to‐moderate childhood asthma Abstract Attention deficit hyperactivity disorder ( ADHD ) belongs to the neurodevelopmental disorders characterized by impulsivity , distractibility and hyperactivity . In the pathogenesis of ADHD genetic and non-genetic factors play an important role . It is assumed that one of non-genetic factors should be oxidative stress . Pycnogenol ® , an extract from the pine bark , consists of bioflavonoids , catechins , procyanidins and phenolic acids . Pycnogenol ® acts as powerful antioxidant , chelating agent ; it stimulates the activities of some enzymes , like SOD , eNOS , and exhibits other biological activities . Aim : The aim of this r and omized , double-blind , placebo-controlled trial was to investigate the influence of administered Pycnogenol ® or placebo on the level of reduced ( GSH ) and oxidized ( GSSG ) glutathione in children suffering from ADHD and on total antioxidant status ( TAS ) . This is the first investigation of the redox glutathione state in relation to ADHD . Results : One month of Pycnogenol ® administration ( 1 mg/kg body weight/day ) caused a significant decrease in GSSG and a highly significant increase in GSH levels as well as improvement of GSH/GSSG ratio in comparison to a group of patients taking a placebo . TAS in children with ADHD was decreased in comparison with reference values . Pycnogenol ® administration normalizes TAS of ADHD children A double-blind , placebo-controlled , r and omized , multi-center study was performed with 77 diabetes type II patients to investigate anti-diabetic effects of the French maritime pine bark extract , Pynogenol . Supplementation with 100 mg Pycnogenol for 12 weeks , during which a st and ard anti-diabetic treatment was continued , significantly lowered plasma glucose levels as compared to placebo . HbA1(c ) was also lowered ; however , the difference as compared to placebo was statistically significant only for the first month . In the Pycnogenol-group endothelin-1 was significantly decreased , while 6-ketoprostagl and in F(1a ) in plasma was elevated compared to placebo . Nitric oxide levels in plasma increased during treatment in both groups , but , differences did not reach statistical significance . Pycnogenol was well-tolerated with ECG , electrolytes , creatinine and blood urea nitrogen remaining unchanged in both groups . Mild and transient unwanted effects were reported for both groups without significant differences . Supplementation of Pycnogenol to conventional diabetes treatment lowers glucose levels and improves endothelial function A pilot study was performed to evaluate the efficacy of Pycnogenol treatment in systemic lupus erythematosus ( SLE ) patients . Eleven SLE patients were treated with first line medication according to disease activity and in addition , six of them received Pycnogenol and five a placebo . The SLE disease activity index ( SLEDAI ) , serum anti-dsDNA antibodies , fibrinogen , C-reactive protein levels , erythrocyte sedimentation rate , production of reactive oxygen species ( ROS ) by neutrophils , spontaneous apoptosis and p56(lck ) specific activity in peripheral blood lymphocytes were evaluated . Pycnogenol treatment determined a significant reduction of ROS production , apoptosis , p56(lck ) specific activity and erythrocyte sedimentation rate . In addition , the decrease of SLEDAI was significant in the Pycnogenol treated group compared with the placebo group ( p = 0.018 ) . The results obtained suggest that Pycnogenol could be useful for second line therapy to reduce the inflammatory feature of SLE The aim of this study was to evaluate the clinical efficacy of st and ardized French maritime pine bark extract Pycnogenol in patients with severe chronic venous insufficiency ( CVI ) . 98 subjects with symptomatic CVI and edema were r and omly assigned to one group treated with 150 mg Pycnogenol a day only , another group with stockings only and a third group with both Pycnogenol and elastic stockings . The average ambulatory venous pressure ( AVP ) at inclusion was 58+/-7 mm Hg ( range 48 - 60 mm Hg ) with a refilling time (RT)<12 s ( average 7+/-2 s ) . The duration of the disease was on average 6.0+/-3.1 years . There were no differences in AVP or RT among the 3 groups at inclusion and microcirculatory and clinical evaluations were comparable . After 8 weeks treatment there was a significant decrease of rate of ankle swelling , resting flux , transcutaneous pO(2 ) and clinical symptom scores in all groups with significantly better results for the combination treatment . Pycnogenol alone was more effective than compression alone for all parameters ( p<0.05 ) . No side-effects were observed ; compliance and tolerability were very good . This study corroborates a significant clinical role for Pycnogenol in the management , treatment and control of CVI also in combination with compression Forty patients with chronic venous insufficiency ( CVI ) and varices of the legs were selected and double-blindly r and omly assigned to a treatment with Pycnogenol ( French maritime pine bark extract ) , 100 mg x 3/day or a placebo for 2 months , according to a double-blind experimental design . The effects of the treatment were evaluated by scoring the symptomatology with a semi-quantitative scale , and the venous blood flow by means of a h and -held Doppler ultrasound . The tolerability was evaluated by recording the adverse effects and by means of hematology and blood chemistry parameters , before and at the end of the treatment . Pycnogenol treatment induced a significant reduction in subcutaneous edema as well as heaviness and pain in the legs , on both after 30 and 60 days , the evaluation time periods . Approximately 60 % of patients treated with Pycnogenol(R ) experienced a complete disappearance of edema ( the most rapidly disappearing symptom ) and pain at the end of the treatment , while almost all the patients reported a reduction in leg heaviness which disappeared in approximately 33 % of patients . These changes were statistically significant . No effect was observed in the placebo-treated subjects . No effect on the venous blood flow was observed in either of the experimental groups Attention Deficit/Hyperactivity Disorder ( ADHD ) is the most common psychiatric disorder in children . Pycnogenol ® , an extract from the bark of the French maritime pine , consisting of phenolic acids , catechin , taxifolin and procyanidins , has shown improvement of ADHD in case reports and in an open study . Aim of the present study was to evaluate the effect of Pycnogenol ® on ADHD symptoms . Sixty-one children were supplemented with 1 mg/kg/day Pycnogenol ® or placebo over a period of 4 weeks in a r and omised , placebo-controlled , doubleblind study . Patients were examined at start of trial , 1 month after treatment and 1 month after end of treatment period by st and ard question naires : CAP ( Child Attention Problems ) teacher rating scale , Conner ’s Teacher Rating Scale ( CTRS ) , the Conner ’s Parent Rating Scale ( CPRS ) and a modified Wechsler Intelligence Scale for children . Results show that 1-month Pycnogenol ® administration caused a significant reduction of hyperactivity , improves attention and visual – motoric coordination and concentration of children with ADHD . In the placebo group no positive effects were found . One month after termination of Pycnogenol ® administration a relapse of symptoms was noted . Our results point to an option to use Pycnogenol as a natural supplement to relieve ADHD symptoms of children The aim of our study was to investigate the effects of Pycnogenol on the progression of diabetic retinopathy and other vascular retinal disorders . The study consisted of a double-blind phase in which 20 patients were recruited and r and omly treated with placebo or Pycnogenol ( 50 mg x 3/day for 2 months ) and an open phase in which another 20 patients were treated with Pycnogenol at the same dose schedule . In total , 40 patients with diabetes , atherosclerosis and other vascular diseases involving the retina were enrolled ; 30 of them were treated with Pycnogenol and 10 with placebo . The results demonstrated a beneficial effect of Pycnogenol on the progression of retinopathy . Without any treatment ( placebo ) the retinopathy progressively worsened during the trial and the visual acuity significantly decreased ; on the contrary , the Pycnogenol-treated patients showed no deterioration of retinal function and a significant recovery of visual acuity was also obtained . The fluorangiography showed an improvement of retinal vascularization and a reduced endothelial permeability and leakage in the Pycnogenol , but not in the placebo-treated , patients . The ophthalmoscopy and the electroretinogram ( ERG ) also confirmed the beneficial effects of Pycnogenol . The mechanism of action of Pycnogenol may be related to its free radical ( FR ) scavenging , anti-inflammatory and capillary protective activities . It has been suggested that Pycnogenol may bind to the blood vessel wall proteins and mucopolysaccharides and produce a capillary ' sealing ' effect , leading to a reduced capillary permeability and oedema formation Abstract Our study tested the hypothesis that treatment with a potent polyphenol complex not only reduces hyperactivity of children , but also catecholamine excretion and oxidative stress . Urine catecholamine concentrations were measured in attention deficit hyperactivity disorder ( ADHD ) children and healthy controls . ADHD children received either placebo ( PL ) or Pycnogenol ® ( Pyc ) , a bioflavonoid extract from the pine bark , for one month . The study was performed in a r and omized , double-blind , PL controlled design . Concentrations of catecholamines were higher in urine of ADHD patients compared to those of healthy children . Moreover , noradrenaline ( NA ) concentrations positively correlated with degree of hyperactivity of ADHD children . In ADHD patients , adrenaline ( A ) and NA concentrations positively correlated with plasma levels of oxidized glutathione . The treatment of ADHD children with Pyc caused decrease of dopamine ( D ) and trend of A and NA decrase and increased GSH/GSSG ratio . In conclusion , the data provide further evidence for the overactivity of the noradrenergic system in ADHD and demonstrate that A release may be increased , as well . Treatment of ADHD children with Pyc normalized catecholamine concentrations , leading to less hyperactivity , and , consequently , to reduced oxidative stress The presence of edema in different phases and stages of essential hypertension may be due to antihypertensive treatment . Some drugs may cause edema by inducing vasodilatation , increasing the capillary exchange surface and capillary filtration . Pycnogenol has an important anti-edema effect in diabetic microangiopathy and chronic venous insufficiency . This 8-week study evaluated capillary filtration in 2 comparable treatment groups with hypertension treated with a calcium antagonist ( nifedipine ) or angiotensin-converting enzyme inhibitor to define its efficacy in preventing edema caused by antihypertensives . A significant decrease in filtration was observed in the Pycnogenol groups . Pycnogenol controls this type of edema , it helps to prevent and limit long-term damage in the microcirculation in hypertensive patients , and allows the dose of anti-hypertensive drugs to be reduced in most patients |
2,244 | 22,161,411 | Adjuvant RT after RP improves overall survival and reduces the rate of distant metastases , but these effects are only evident with longer follow up .
At 5 and 10 years it improves local control and reduces the risk of biochemical failure , although the latter is not a clinical endpoint .
Moderate or severe acute and late toxicity is minimal .
There is an increased risk of urinary stricture and incontinence , but no detriment to quality of life , based on limited data . | BACKGROUND Men who have a radical prostatectomy ( RP ) for prostate cancer that does not involve lymph nodes , but extends beyond the prostate capsule into the seminal vesicles or to surgical margins , are at increased risk of relapse .
In men with these high risk factors , radiotherapy ( RT ) directed at the prostate bed after surgery may reduce this risk , and be curative .
OBJECTIVES To evaluate the effect of adjuvant RT following RP for prostate cancer in men with high risk features compared with RP . | PURPOSE Local failure after radiotherapy can arise with cancer extending beyond the capsule and /or involvement of seminal vesicles or positive surgical margins . METHODOLOGY After undergoing radical prostatectomy 1005 patients were r and omly assigned ( 1999 - 2001 ) to a wait and see policy or an immediate postoperative irradiation ( 60 Gy delivered over 6 weeks ) ; eligible patients had pN0 M0 tumors and one or more pathological risk factors mentioned above . The main end-point was 5-year biochemical progression free survival . RESULTS After a median follow-up of 5-year biochemical progression free survival was significantly improved in the irradiated group ( 74 % , 98 % CI : 68.7 - 79.3 vs 52.6 % , 98 % CI : 46.6 - 58.5 ; P<0.0001 ) Clinical progression free survival was also significantly improved ( P<0.0009 ) . The cumulative rate of loco-regional failure was also significantly improved ( P<0.0009 ) . Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group ( P=0.0005 ) , but severe toxicity ( grade 3 or higher ) were rare with a 5-year rate of 2.6 % in the wait- and -see group and 4.2 % in the postoperative irradiation group ( P=0.07 ) . CONCLUSION Immediate external irradiation after radical prostatectomy improves biochemical progression free survival and local control in patients with positive surgical margin or pT3 prostate cancer who are at high risk of progression . Further follow-up is needed to assess the impact on overall survival BACKGROUND Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule . We did a r and omised controlled trial to compare radical prostatectomy followed by immediate external irradiation with prostatectomy alone for patients with positive surgical margin or pT3 prostate cancer . METHODS After undergoing radical retropubic prostatectomy , 503 patients were r and omly assigned to a wait- and -see policy , and 502 to immediate postoperative radiotherapy ( 60 Gy conventional irradiation delivered over 6 weeks ) . Eligible patients had pN0M0 tumours and one or more pathological risk factors : capsule perforation , positive surgical margins , invasion of seminal vesicles . Our revised primary endpoint was biochemical progression-free survival . Analysis was by intention to treat . FINDINGS The median age was 65 years ( IQR 61 - 69 ) . After a median follow-up of 5 years , biochemical progression-free survival was significantly improved in the irradiated group ( 74.0 % , 98 % CI 68.7 - 79.3 vs 52.6 % , 46.6 - 58.5 ; p<0.0001 ) . Clinical progression-free survival was also significantly improved ( p=0.0009 ) . The cumulative rate of locoregional failure was significantly lower in the irradiated group ( p<0.0001 ) . Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group ( p=0.0005 ) , but severe toxic toxicity ( grade 3 or higher ) were rare , with a 5-year rate of 2.6 % in the wait- and -see group and 4.2 % in the postoperative irradiation group ( p=0.0726 ) . INTERPRETATION Immediate external irradiation after radical prostatectomy improves biochemical progression-free survival and local control in patients with positive surgical margins or pT3 prostate cancer who are at high risk of progression . Further follow-up is needed to assess the effect on overall survival OBJECTIVES To define the optimal role for radiotherapy ( RT ) after radical prostatectomy ( RP ) and to characterize specific patterns of PSA failure in this setting . METHODS The records of 105 patients who underwent RT after RP ( 69 received therapeutic RT because of an elevated prostate-specific antigen [ PSA ] level , 36 received immediate adjuvant RT ) were review ed . The median follow-up was 35 months after RT and 57 months after RP . Radiation success was defined as achievement and maintenance of a PSA less than 0.2 ng/mL. Preoperative , pathologic , and postoperative characteristics were examined for their ability to predict success after RT . Patterns of PSA recurrence after RT were also examined by determining the PSA nadir , PSA velocity , and timing of and rogen-deprivation therapy . RESULTS Of 105 patients , 47 experienced biochemical failure . Actuarial 3 and 5-year progression-free survival estimates for all patients were 55 % and 43 % , respectively . Significant favorable predictors of response to RT by multivariate analysis were preoperative PSA less than 20 ng/mL and the use of adjuvant RT . However , patients who received therapeutic RT with a pre-RT PSA less than 1.0 ng/mL demonstrated progression-free outcome equivalent to those who received adjuvant RT . Two distinct patterns of PSA failure were observed on the basis of PSA nadir after RT . Patients whose PSA failed to reach a nadir less than 0.2 ng/mL after RT had progression with a high PSA velocity ( 1.5 ng/mL/yr ) . Patients whose PSA reached a nadir less than 0.2 ng/mL but who subsequently had treatment failure progressed later with a lower PSA velocity ( 0.36 ng/ml/yr ) . CONCLUSIONS RT is effective in select patients after RP . Given the low PSA velocity consistent with persistent local disease in nearly 50 % of patients in whom RT failed , more effective local therapy is needed after RP in high-risk patients INTRODUCTION A dry run of a clinical trial ( EORTC 22911 ) is presented in which 12 centres have participated . These are the centres which have contributed the largest number of patients to the trial . MATERIAL AND METHODS Each participating centre received data from a suitable patient . Investigators were asked to plan and ' treat ' the patient according to the protocol guidelines and return the data for evaluation of compliance . RESULTS The results show that compliance to the protocol guidelines was generally good . There were a few minor deviations in the dose and fractionation schedule , in the volume reduction for the booster dose and in the dose prescription point . None of these deviations will affect the outcome of the study . The most important observation is the large inter-centre variation in target volumes . CONCLUSIONS The results of this study underlines the need for a strict definition of the target volume and the adoption of the ICRU 50 recommendations in future protocol Pathological staging and surgical margin status of radical prostatectomy specimens are next to grading the most important prognosticators for recurrence . A central review of pathological stage and surgical margin status was performed on a series of 552 radical prostatectomy specimens of patients , participating in the European Organisation for Research and Treatment of Cancer trial 22911 . Inclusion criteria of the trial were pathological stage pT3 and /or positive surgical margin at local pathology . All specimens were totally embedded . Data of the central review were compared with those of local pathologists and related to clinical follow-up . Although a high concordance between review pathology and local pathologists existed for seminal vesicle invasion ( 94 % , κ=0.83 ) , agreement was much less for extraprostatic extension ( 57.5 % , κ=0.33 ) and for surgical margin status ( 69.4 % , κ=0.45 ) . Review pathology of surgical margin status was a stronger predictor of biochemical progression-free survival in univariate analysis [ hazard ratio (HR)=2.16 and p=0.0002 ] than local pathology ( HR=1.08 and p>0.1 ) . The review pathology demonstrated a significant difference between those with and without extraprostatic extension ( HR=1.83 and p=0.0017 ) , while local pathology failed to do so ( HR=1.05 and p>0.8 ) . The observations suggest that review of pathological stage and surgical margin of radical prostatectomy strongly improves their prognostic impact in multiinstitutional studies or trials PURPOSE Southwest Oncology Group ( SWOG ) trial 8794 demonstrated that adjuvant radiation reduces the risk of biochemical ( prostate-specific antigen [ PSA ] ) treatment failure by 50 % over radical prostatectomy alone . In this analysis , we stratified patients as to their preradiation PSA levels and correlated it with outcomes such as PSA treatment failure , local recurrence , and distant failure , to serve as guidelines for future research . PATIENTS AND METHODS Four hundred thirty-one subjects with pathologically advanced prostate cancer ( extraprostatic extension , positive surgical margins , or seminal vesicle invasion ) were r and omly assigned to adjuvant radiotherapy or observation . RESULTS Three hundred seventy-four eligible patients had immediate postprostatectomy and follow-up PSA data . Median follow-up was 10.2 years . For patients with a postsurgical PSA of 0.2 ng/mL , radiation was associated with reductions in the 10-year risk of biochemical treatment failure ( 72 % to 42 % ) , local failures ( 20 % to 7 % ) , and distant failures ( 12 % to 4 % ) . For patients with a postsurgical PSA between higher than 0.2 and < or = 1.0 ng/mL , reductions in the 10-year risk of biochemical failure ( 80 % to 73 % ) , local failures ( 25 % to 9 % ) , and distant failures ( 16 % to 12 % ) were realized . In patients with postsurgical PSA higher than 1.0 , the respective findings were 94 % versus 100 % , 28 % versus 9 % , and 44 % versus 18 % . CONCLUSION The pattern of treatment failure in high-risk patients is predominantly local with a surprisingly low incidence of metastatic failure . Adjuvant radiation to the prostate bed reduces the risk of metastatic disease and biochemical failure at all postsurgical PSA levels . Further improvement in reducing local treatment failure is likely to have the greatest impact on outcome in high-risk patients after prostatectomy 4504 Background : In 1992 , as radical prostatectomy was more frequently applied to clinical T1 - 2N0M0 prostate cancer , the EORTC has undertaken a r and omized trial of immediate post-operative treatment versus wait- and -see policy , for patients with high risk factors of local relapse on pathological specimen . We present the first efficacy results of this study . METHODS Eligible patients were ≤75 years old , WHO performance status ( PS ) 0 - 1 , had T0 - 3N0M0 PC preoperatively and ≥1 pathological risk factor of : capsule invasion , positive surgical margins , invasion of seminal vesicles . P-XRT was 60Gy conventional external radiation delivered over 6 weeks . The trial was powered to detect a hazard ratio ( HR ) of 0.77 with 80 % power with two-sided α=0.05 with regard to clinical or biological progression-free survival . RESULTS 1005 pts were accrued by end 2001 ( P-XRT : 503 , Px : 502 ) . Median age was 65.4 years , PS 0 in 93.8 % , median pre- and post-operative PSA 12.3 and 0.2 ng/ml , respectively . All but 41pts on P-XRT were irradiated with median dose 60Gy ( range : 50 - 74 ) . The trial was review ed by an IDMC in December 2003 , after a median follow-up of 5 years and early disclosure of the trial results was recommended . Biochemical PFS ( time to twice confirmed PSA increase over nadir or first clinical failure or death ) at 5 years was 72.2 % ( CI : 67.7 - 76.8 ) on P-XRT and 51.8 % ( CI : 46.8 - 56.8 ) , HR=0.52 ( CI : 0.42 - 0.64 ) , P<0.0001 . Clinical PFS was improved from 74.8 % to 83.3 % at 5 years ( HR=0.68 , CI : 0.52 - 0.89 , P=0.004 ) . The incidence of loco-regional failure was significantly decreased ( P<0.0001 ) . Further follow-up is needed to assess the impact on distant metastases and overall survival . P-XRT is associated with an increased risk of immediate and late grade 1 - 2 side effects . Grade 3 side effect rates so far were less than 5 % in both groups . CONCLUSIONS Post-operative radiotherapy results in improved biochemical and clinical PFS . This benefit is to be weighed against the treatment side effects . Further follow-up is needed to assess the impact on overall survival . No significant financial relationships to disclose As professionals , we want to use the best treatments ; as patients , we want to be given them . Knowing whether an intervention works ( or does not work ) is fundamental to clinical decision making . However , clinical decision making involves more than simply taking published results of research directly to the bedside . Physicians need to consider how similar their patients are to those in the published studies , to take the values and preferences of their patients into account , and to consider their own experience with a given test or treatment . Evidence from clinical research is becoming increasingly important in medical- practice decisions as more and better evidence is published . But when is the evidence strong enough to justify changing a practice ? Individual studies that involve only small numbers of patients may have results that are distorted by the r and om play of chance and thus lead to less than optimal decisions . As is clear from other papers in this series , systematic review s identify , critically appraise , and review all the relevant studies on a clinical question and are more likely to give a valid answer . They use explicit methods and quality st and ards to reduce bias . Their results are the closest we can come to reaching the truth given our current state of knowledge . The questions about an intervention that a systematic review should answer are the following : 1 . Does it work ? 2 . If it works , how well does it work in general and compared with placebo , no treatment , or other interventions that are currently in use ? 3 . Is it safe ? 4 . Will it be safe and effective for my patients ? Whereas the critical appraisal and qualitative synthesis provided by review articles can be interpreted directly , the numerical products of quantitative review s can be more difficult to underst and and apply in daily clinical practice . This paper provides guidance on how to interpret the numerical and statistical results of systematic review s , translate these results into more underst and able terms , and apply them directly to individual patients . Many of these principles can also be used to interpret the numerical results of individual clinical studies . They are particularly relevant to systematic review s , however , because such review s contain more information than do primary studies and often exert greater influence than do individual studies . Making Sense of the Numerical Results of Clinical Studies Although the results of clinical studies can be expressed in intuitively meaningful ways , such results do not always easily translate into clinical decision making . For example , results are frequently expressed in terms of risk , which is an expression of the frequency of a given outcome . ( Risks are probabilities , which can vary between 0.0 and 1.0 . A probability of 0.0 means that the event will never happen , and a probability of 1.0 means that it always happens . ) Consider a hypothetical study of the recurrence of migraine headaches in a control group receiving placebo and a treatment group receiving a new antimigraine preparation , drug M ( a secondary prevention trial ) . Suppose that at the end of the trial , migraines recurred in 30 % of the control group ( the risk for recurrence was 0.30 ) but in only 5 % of the drug M group ( risk of 0.05 ) ( Table 1 ) . Table 1 . Numerical Expression of Hypothetical Clinical Trial Results The outcomes of the study are clear enough for the two groups when they are examined separately . But clinicians and patients are more interested in the comparative results , that is , the outcome in one group relative to the outcome in the other group . This overall ( comparative ) result can be expressed in various ways . For example , the relative risk , which is the risk in the treatment group relative to that in the control group , is simply the ratio of the risks in the two groups . In other words , relative risk is the risk in the treatment group divided by that in the control group , 0.05 0.30 , or 0.17 . The comparison can also be expressed as the reduction in relative risk , which is the ratio between the decrease in risk ( in the treatment group ) and the risk in the control group , 0.25 0.30 , or 0.83 ( Table 1 ) . ( The relative risk reduction can also be calculated as 1 relative risk ) . Although the clinical meaning of relative risk ( and relative risk reduction ) is reasonably clear , relative risk has the distinct disadvantage that a given value ( for example , 0.17 ) is the same whether the risk with treatment decreases from 0.80 to 0.14 , from 0.30 to 0.05 , from 0.001 to 0.00017 , and so forth . The clinical implication s of these changes clearly differ from one another enormously and depend on the specific disease and intervention . An important alternate expression of comparative results , therefore , is the absolute risk reduction . Absolute risk reduction is determined by subtracting the risk in one group from the risk in the other ( for example , the risk in the treatment group is subtracted from the risk in the placebo group ) . In the case of our migraine study , the absolute risk reduction would be 0.30 0.05 , which equals 0.25 , or 25 percentage points . In contrast , for a study in which the risk decreased from 0.001 to 0.00017 , the absolute risk reduction would be only 0.00083 , or 0.083 percentage points , which is a trivial change in comparison ( Table 1 ) . This arithmetic emphasizes the difficulty of expressing the results of clinical studies in meaningful ways . Relative risk and relative risk reduction clearly give a quantitative sense of the effects of an intervention in proportional terms but provide no clue about the size of an effect on an absolute scale . In contrast , although it tells less about proportional effects , absolute risk says a great deal about whether an effect is likely to be clinical ly meaningful . Despite this benefit , even absolute risk is problematic because it is a dimensionless , abstract number ; that is , it lacks a direct connection with the clinical situation in which the patient and physician exist . However , another way of expressing clinical research results can provide that clinical link : the number needed to treat ( NNT ) . Number Needed To Treat The NNT for a given therapy is simply the reciprocal of the absolute risk reduction for that treatment [ 1 , 2 ] . In the case of our hypothetical migraine study ( in which risk decreased from 0.30 without treatment with drug M to 0.05 with treatment with drug M , for a relative risk of 0.17 , a relative risk reduction of 0.83 , and an absolute risk reduction of 0.25 ) , the NNT would be 1 0.25 , or 4 . In concrete clinical terms , an NNT of 4 means that you would need to treat four patients with drug M to prevent migraine from recurring in one patient . To emphasize the difference between the concepts embodied in NNT and relative risk , recall the various situations mentioned above , in all of which the relative risk was 0.17 but in which the absolute risk decreased from 0.80 to 0.14 in one case and from 0.001 to 0.00017 in another . Note that the corresponding NNTs in these two other cases are 1.5 and 1204 , respectively : that is , you would need to treat 1.5 and 1204 patients to obtain a therapeutic result in these two situations compared with 4 patients with drug M ( Table 1 ) . The NNT can be calculated easily and kept as a single numerical reminder of the effectiveness ( or , as we will see , the potential for harm ) of a particular therapy . As we suggested , the NNT has the crucial advantage of direct applicability to clinical practice because it shows the effort that is required to achieve a particular therapeutic target . The NNT has the additional advantage that it can be applied to any beneficial outcome or any adverse event ( when it becomes the number needed to harm [ NNH ] ) . The concept of NNT always refers to a comparison group ( in which patients receive placebo , no treatment , or some other treatment ) , a particular treatment outcome , and a defined period of treatment . In other words , the NNT is the number of patients that you will need to treat with drug or treatment A to achieve an improvement in outcome compared with drug or treatment B for a treatment period of C weeks ( or other unit of time ) . To be fully specified , NNT and NNH must always specify the comparator , the therapeutic outcome , and the duration of treatment that is necessary to achieve the outcome . Important Qualities of the Number Needed To Treat The NNT is treatment specific . It describes the difference between treatment and control in achieving a particular clinical outcome . Table 2 shows NNTs from a selection of systematic review s and large r and omized , controlled trials . Table 2 . Numbers Needed To Treat from Systematic Review s and R and omized , Controlled Trials A very small NNT ( that is , one that approaches 1 ) means that a favorable outcome occurs in nearly every patient who receives the treatment and in few patients in a comparison group . Although NNTs close to 1 are theoretically possible , they are almost never found in practice . However , small NNTs do occur in some therapeutic trials , such as those comparing antibiotics with placebo in the eradication of Helicobacter pylori infection or those examining the use of insecticide for head lice ( Table 2 ) . An NNT of 2 or 3 indicates that a treatment is quite effective . In contrast , such prophylactic interventions as adding aspirin to streptokinase to reduce 5-week vascular mortality rates after myocardial infa rct ion may have NNTs as high as 20 to 40 and still be considered clinical ly effective . Limitations of the Number Needed To Treat Although NNTs are powerful instruments for interpreting clinical effects , they also have important limitations . First , an NNT is generally expressed as a single number , which is known as its point estimate . As with all experimental measurements , however , the true value of the NNT can be higher or lower than the point estimate determined through clinical studies . The 95 % CIs of the NNT are useful in this regard because they provide an indication that OBJECTIVES We analysed the acute toxicity observed in the European Organisation for Research and Treatment of Cancer ( EORTC ) r and omised trial 22863 comparing conventional external irradiation with or without an agonist analogue of gonadotropin-releasing hormone in high-risk prostate cancer patients . METHODS Four hundred five patients that received a dose of at least 30 Gy were considered evaluable for acute toxicity assessment . Toxicity was grouped in a few categories : general , genito-urinary , and lower gastro-intestinal . Univariate and multivariate analyses were performed using the World Health Organisation ( WHO ) toxicity score and grouping together toxicity scores in different bimodal and trimodal groups . RESULTS Overall , our data show that age , previous surgery and irradiation dose are important predictive factors for acute toxicity , but not the use of combined hormone therapy . Fifteen percent of patients suffered of moderate to severe acute toxicity ( WHO G3-G4 ) . Life threatening toxicity was observed in six cases ( 1.5 % ) . CONCLUSIONS The assessment of toxicity combining in different groups the original five scores scale produced conflicting results similar to those commonly reported in literature . Interpretation of the role of pre-treatment factors with uneven distribution in the study requires careful evaluation . These data obtained with conventional curative irradiation of high-risk prostate cancer patients are proposed for comparison with results achieved using modern state-of-the-art irradiation techniques BACKGROUND AND PURPOSE Three r and omised trials have demonstrated the benefit of adjuvant post-prostatectomy radiotherapy ( PPRT ) for high risk patients . Data also documents the effectiveness of salvage radiotherapy following a biochemical relapse post-prostatectomy . The Radiation Oncology Genito-Urinary Group recognised the need to develop consensus guidelines on to whom , when and how to deliver PPRT . MATERIAL S AND METHODS Draft guidelines were developed and refined at a consensus conference in June 2006 attended by 63 delegates where urological , radiotherapy and diagnostic imaging experts spoke on aspects of PPRT . Unresolved issues were further developed by working parties and redistributed until consensus was reached . RESULTS Central to the recommendations is that patients with positive surgical margins , seminal vesicle invasion and /or extracapsular extension have a high risk of residual local disease and should be informed of the options of either immediate adjuvant radiotherapy or active surveillance with early salvage in the event of biochemical recurrence . Salvage radiotherapy should be instituted at the earliest confirmation of biochemical recurrence . Detailed contouring guidelines have been developed , defining the regions at risk of residual microscopic disease which should be included in the clinical target volume . The recommended doses are 60 - 64Gy for adjuvant , and 60 - 66Gy for salvage radiotherapy . The role of hormone therapy in conjunction with PPRT is yet to be defined . CONCLUSIONS These consensus guidelines have been developed to give clinical and technical guidance to radiation oncologists and urologists in the management of high risk post-prostatectomy patients PURPOSE Radiation Therapy Oncology Group protocol 85 - 31 was design ed to evaluate the effectiveness of adjuvant and rogen suppression , using goserelin , in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy ( RT ) . METHODS AND MATERIAL S Eligible patients were those with palpable primary tumor extending beyond the prostate ( clinical Stage T3 ) or those with regional lymphatic involvement . Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and /or seminal vesicle involvement was documented histologically . Stratification was based on histologic differentiation , nodal status , acid phosphatase status , and prior prostatectomy . The patients were r and omized to either RT and adjuvant goserelin ( Arm I ) or RT alone followed by observation and application of goserelin at relapse ( Arm II ) . In Arm I , the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression . RESULTS Between 1987 and 1992 , when the study was closed , 977 patients were entered : 488 to Arm I and 489 to Arm II . As of July 2003 , the median follow-up for all patients was 7.6 years and for living patients was 11 years . At 10 years , the absolute survival rate was significantly greater for the adjuvant arm than for the control arm : 49 % vs. 39 % , respectively ( p = 0.002 ) . The 10-year local failure rate for the adjuvant arm was 23 % vs. 38 % for the control arm ( p < 0.0001 ) . The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24 % vs. 39 % ( p < 0.001 ) and 16 % vs. 22 % ( p = 0.0052 ) , respectively , both in favor of the adjuvant arm . CONCLUSION In a population of patients with unfavorable prognosis carcinoma of the prostate , and rogen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival . The improvement in survival appeared preferentially in patients with a Gleason score of 7 - 10 EORTC trial 22911 demonstrated that immediate postoperative irradiation significantly improved biochemical failure free survival ( BPFS ) compared to wait- and -see ( W and S ) until relapse in patients with pT2 - 3 tumours and pathological risk factors after radical prostatectomy . In this study , we have investigated the heterogeneity of the treatment benefit across defined subgroups of patients . Data from 972 patients were used . A risk model was developed in the W and S group and the Log-rank test for heterogeneity was applied ( alpha=0.05 ) . Positive surgical margin ( SM+ ) , seminal vesicle invasion ( SV+ ) , WHO differentiation grade , pre- and post-operative PSA were independent predictors for BPFS in the W and S group . Men with SV+ were at higher risk of relapse whereas those with SM+ but no capsule infiltration ( ECE- ) did not seem to differ from those with SM-ECE+ or with SM+ECE+ . Postoperative irradiation improved biochemical progression-free survival in all patient groups . Longer follow-up is needed to assess the endpoint of clinical progression-free survival PURPOSE Local failure after radical prostatectomy ( RP ) is common in patients with cancer extending beyond the capsule . Two r and omized trials demonstrated an advantage for adjuvant radiotherapy ( RT ) compared with a wait- and -see policy . We conducted a r and omized , controlled clinical trial to compare RP followed by immediate RT with RP alone for patients with pT3 prostate cancer and an undetectable prostate-specific antigen ( PSA ) level after RP . METHODS After RP , 192 men were r and omly assigned to a wait- and -see policy , and 193 men were assigned to immediate postoperative RT . Eligible patients had pT3 pN0 tumors . Patients who did not achieve an undetectable PSA after RP were excluded from treatment according to r and om assignment ( n = 78 ; 20 % ) . Of the remaining 307 patients , 34 patients on the RT arm did not receive RT and five patients on the wait- and -see arm received RT . Therefore , 114 patients underwent RT and 154 patients were treated with a wait- and -see policy . The primary end point was biochemical progression-free survival . RESULTS Biochemical progression-free survival after 5 years in patients with undetectable PSA after RP was significantly improved in the RT group ( 72 % ; 95 % CI , 65 % to 81 % ; v 54 % , 95 % CI , 45 % to 63 % ; hazard ratio = 0.53 ; 95 % CI , 0.37 to 0.79 ; P = .0015 ) . On univariate analysis , Gleason score more than 6 and less than 7 , PSA before RP , tumor stage , and positive surgical margins were predictors of outcome . The rate of grade 3 to 4 late adverse effects was 0.3 % . CONCLUSION Adjuvant RT for pT3 prostate cancer with postoperatively undetectable PSA significantly reduces the risk of biochemical progression . Further follow-up is needed to assess the effect on metastases-free and overall survival PURPOSE To test the hypothesis that and rogen ablation before and during radiotherapy for locally advanced carcinoma of the prostate may , by reducing tumor bulk and enhancing tumor cell kill , improve locoregional control and ultimately survival . METHODS AND MATERIAL S The study was conducted from 1987 to 1991 . Eligible patients were those with bulky tumors ( T2 - -T4 ) with or without pelvic lymph node involvement and without evidence of distant metastases . They were r and omized to receive goserelin , 3.6 mg every 4 weeks ; and flutamide , 250 mg t.i.d . for 2 months before radiation therapy and during radiation therapy ( Arm I ) , or radiation therapy alone ( Arm II ) . Of 471 r and omized patients , 456 were evaluable : 226 on Arm I and 230 on Arm II . RESULTS As of November 1999 , the median follow-up has reached 6.7 years for all patients and 8.6 years for alive patients . At 8 years , and rogen ablation has been associated with an improvement in local control ( 42 % vs. 30 % , p = 0.016 ) , reduction in the incidence of distant metastases ( 34 % vs. 45 % , p = 0.04 ) , disease-free survival ( 33 % vs. 21 % , p = 0.004 ) , biochemical disease-free survival = PSA < 1.5 ( 24 % vs. 10 % , p < 0.0001 ) , and cause-specific mortality ( 23 % vs. 31 % , p = 0.05 ) . However , subset analysis indicates that the beneficial effect of short-term and rogen ablation appears preferentially in patients with Gleason score 2 - -6 . In that population , there is a highly significant improvement in all endpoints , including survival ( 70 % vs. 52 % , p = 0.015 ) . In patients with Gleason 7 - -10 tumors , the regimen has not result ed in a significant enhancement in either locoregional control or survival . CONCLUSION In patients with Gleason score 2 - -6 carcinoma of the prostate , a short course of and rogen ablation administered before and during radiotherapy has been associated with a highly significant improvement in local control , reduction in disease progression , and overall survival PURPOSE We analyzed the potential influence of adjuvant radiotherapy on urinary continence after radical prostatectomy . MATERIAL S AND METHODS A total of 100 patients with N0M0 prostate cancer r and omized in a prospect i ve study on postoperative radiotherapy for locally advanced disease ( positive surgical margin , capsular perforation and /or seminal vesicle infiltration ) were studied . Objective pad weighing tests corroborated by direct personal interviews were used to evaluate urinary continence at regular postoperative intervals . RESULTS Of the patients 48 received 60 Gy . external radiotherapy with 18 MV photon beams between 12 and 16 weeks postoperatively , and 52 were followed expectantly . Risk factors were similar in both groups . With a mean followup of 24 months , no difference in complete urinary continence was observed . Of the irradiated group 77 % and of the surveillance group 83 % were totally dry . The fate of the bladder neck had no significant influence on final continence status , although there was a trend for faster recovery when the bladder neck was preserved . CONCLUSIONS In this prospect i ve r and omized study 60 Gy . external radiation therapy administered between 3 and 4 months after radical prostatectomy for pathologically locally advanced prostate cancer had no significant influence on urinary continence BACKGROUND Appropriate timing of and rogen deprivation treatment ( ADT ) for prostate cancer is controversial . Our aim was to determine whether immediate ADT extends survival in men with node-positive prostate cancer who have undergone radical prostatectomy and pelvic lymphadenectomy compared with those who received ADT only once disease progressed . METHODS Eligible patients from 36 institutes in the USA were r and omly assigned in 1988 - 93 to receive immediate ADT ( n=47 ) or to be observed ( n=51 ) , with ADT to be given on detection of distant metastases or symptomatic recurrences . Patients were followed up every 3 months for the first year and every 6 months thereafter . The primary endpoint was progression-free survival ; secondary endpoints were overall and disease-specific survival . Analysis was by intention to treat . To ensure that the treatment groups were comparable , we did a retrospective central pathology review of slides and re grade d the Gleason scores for available sample s. This trial pre date s the requirement for clinical trial registration . FINDINGS At median follow-up of 11.9 years ( range 9.7 - 14.5 for surviving patients ) , men assigned immediate ADT had a significant improvement in overall survival ( hazard ratio 1.84 [ 95 % CI 1.01 - 3.35 ] , p=0.04 ) , prostate-cancer-specific survival ( 4.09 [ 1.76 - 9.49 ] , p=0.0004 ) , and progression-free survival ( 3.42 [ 1.96 - 5.98 ] , p<0.0001 ) . Of 49 histopathology slides received ( 19 immediate ADT , 30 observation ) , 16 were down grade d from the original Gleason score ( between groups < or = 6 , 7 , and > or = 8) and five were up grade d. We recorded similar proportions of score changes in each group ( p=0.68 ) , and no difference in score distribution by treatment ( p=0.38 ) . After adjustment for score , associations were still significant between treatment and survival ( overall , p=0.02 ; disease-specific , p=0.002 ; progression-free survival , p<0.0001 ) . INTERPRETATION Early ADT benefits patients with nodal metastases who have undergone prostatectomy and lymphadenectomy , compared with those who receive deferred treatment . The beneficial effects of early ADT , rather than an imbalance in risk factors , are likely to explain the differences in outcomes between treatments Radiotherapy and and rogen deprivation in combination after local surgery ( RADICALS ) : A new Medical Research Council/National Cancer Institute of Canada phase III trial of adjuvant treatment after radical prostatectomy Chris Parker , Matthew R. Sydes 1 , Charles Catton 2 , Howard Kynaston 3 , John Logue , Claire Murphy 1 , Rachel C. Morgan 1 , Kilian Mellon 5 , Chris Morash 6 , Wendy Parulekar 7 , Mahesh K.B. Parmar 1 , Heather Payne 8 , Colleen Savage 7 , Jim Stansfeld 9 and Noel W. Clarke 10 ( The RADICALS Trial Management Group ) Academic Unit of Radiotherapy & Oncology , Institute of Cancer Research and the Royal , Marsden NHS Foundation Trust , Sutton , Surrey , 1 Medical Research Council ( MRC ) Clinical Trials Unit , London , UK , 2 Princess Margaret Hospital , Toronto , Ontario , Canada , 3 Department of Urology , University Hospital of Wales , Heath Park , Cardiff , 4 Christie Hospital NHS Trust , Manchester , UK , 5 Urology Section , University of Leicester , UK , 6 University of Ottawa , The Ottawa Hospital General Campus , Ottawa , 7 National Cancer Institute of Canada ( NCIC ) Clinical Trials Group , Kingston , Ontario , Canada , 8 Department of Oncology , University College Hospital , London , UK , 9 Hon . Treasurer , PCaSO Prostate Cancer Network , Emsworth , Hants , UK , 10 Salford Royal Hospitals NHS Trust , Salford , BACKGROUND Radical radiotherapy is commonly used to treat localised prostate cancer . Late chronic side-effects limit the dose that can be given , and may be linked to the volume of normal tissues irradiated . Conformal radiotherapy allows a smaller amount of rectum and bladder to be treated , by shaping the high-dose volume to the prostate . We assessed the ability of this new technology to lessen the risk of radiation-related effects in a r and omised controlled trial of conformal versus conventional radiotherapy . METHODS We recruited men with prostate cancer for treatment with a st and ard dose of 64 Gy in daily 2 Gy fractions . The men were r and omly assigned conformal or conventional radiotherapy treatment . The primary endpoint was the development of late radiation complications ( > 3 months after treatment ) measured with the Radiation Therapy and Oncology Group ( RTOG ) score . Indicators of disease ( cancer ) control were also recorded . FINDINGS In the 225 men treated , significantly fewer men developed radiation-induced proctitis and bleeding in the conformal group than in the conventional group ( 37 vs 56 % > or = RTOG grade 1 , p=0.004 ; 5 vs 15 % > or = RTOG grade 2 , p=0.01 ) . There were no differences between groups in bladder function after treatment ( 53 vs 59 % > or = grade 1 , p=0.34 ; 20 vs 23 % > or = grade 2 , p=0.61 ) . After median follow-up of 3.6 years there was no significant difference between groups in local tumour control ( conformal 78 % [ 95 % CI 66 - 86 ] , conventional 83 % [ 69 - 90 ] ) . INTERPRETATION Conformal techniques significantly lowered the risk of late radiation-induced proctitis after radiotherapy for prostate cancer . Widespread introduction of these radiotherapy treatment methods is appropriate . Our results are the basis for dose-escalation studies to improve local tumour control RADICALS is a large , international r and omised controlled trial addressing two of the most important questions in postoperative management after radical prostatectomy : the timing of postoperative radiotherapy ( immediate vs early salvage ) and the duration of hormone therapy ( none vs short term vs long term ) used in addition to prostate bed radiotherapy . It has been funded by the Clinical Trials Awards Advisory Committee and will be run by the Medical Research Council Clinical Trials Unit , in collaboration with the National Cancer Institute of Canada Clinical Trials Group and the Trial Management Group . Additional international collaborative groups are also being invited to take part . RADICALS is an ambitious trial , aim ing to recruit over 4000 patients . Widespread support from the urological and oncological communities will be required . More information relating to this study is available from the Medical Research Council Clinical Trials Unit via : [email protected] . © 2007 The Royal College of Radiologists BACKGROUND We did a r and omised phase III trial comparing external irradiation alone and external irradiation combined with an analogue of luteinising-hormone releasing hormone ( LHRH ) to investigate the added value of long-term and rogen suppression in locally advanced prostate cancer . METHODS Between 1987 and 1995 , 415 patients were r and omly assigned radiotherapy alone or radiotherapy plus immediate and rogen suppression . Eligible patients had T1 - 2 tumours of WHO grade 3 or T3 - 4 N0 - 1 M0 tumours ; the median age of participants was 71 years ( range 51 - 80 ) . In both treatment groups , 50 Gy radiation was delivered to the pelvis over 5 weeks , and 20 Gy over 2 weeks as a prostatic boost . Goserelin ( 3.6 mg subcutaneously every 4 weeks ) was started on the first day of irradiation and continued for 3 years ; cyproterone acetate ( 150 mg orally ) was given for 1 month starting 1 week before the first goserelin injection . The primary endpoint was clinical disease-free survival . Analyses were by intention to treat . FINDINGS 412 patients had evaluable data , with median follow-up of 66 months ( range 1 - 126 ) . 5-year clinical disease-free survival was 40 % ( 95 % CI 32 - 48 ) in the radiotherapy-alone group and 74 % ( 67 - 81 ) in the combined-treatment group ( p=0.0001 ) . 5-year overall survival was 62 % ( 52 - 72 ) and 78 % ( 72 - 84 ) , respectively ( p=0.0002 ) and 5-year specific survival 79 % ( 72 - 86 ) and 94 % ( 90 - 98 ) . INTERPRETATION Immediate and rogen suppression with an LHRH analogue given during and for 3 years after external irradiation improves disease-free and overall survival of patients with locally advanced prostate cancer CONTEXT Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer , pathologically advanced disease is detected at radical prostatectomy in 38 % to 52 % of patients . However , the optimal management of these patients after radical prostatectomy is unknown . OBJECTIVE To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 N0 M0 prostate cancer . DESIGN , SETTING , AND PATIENTS R and omized , prospect i ve , multi-institutional , US clinical trial with enrollment between August 15 , 1988 , and January 1 , 1997 ( with data base frozen for statistical analysis on September 21 , 2005 ) . Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy . INTERVENTION Men were r and omly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa ( n = 214 ) or usual care plus observation ( n = 211 ) . MAIN OUTCOME MEASURES Primary outcome was metastasis-free survival , defined as time to first occurrence of metastatic disease or death due to any cause . Secondary outcomes included prostate-specific antigen ( PSA ) relapse , recurrence-free survival , overall survival , freedom from hormonal therapy , and postoperative complications . RESULTS Among the 425 men , median follow-up was 10.6 years ( interquartile range , 9.2 - 12.7 years ) . For metastasis-free survival , 76 ( 35.5 % ) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died ( median metastasis-free estimate , 14.7 years ) , compared with 91 ( 43.1 % ) of 211 ( median metastasis-free estimate , 13.2 years ) of those in the observation group ( hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.55 - 1.02 ; P = .06 ) . There were no significant between-group differences for overall survival ( 71 deaths , median survival of 14.7 years for radiotherapy vs 83 deaths , median survival of 13.8 years for observation ; HR , 0.80 ; 95 % CI , 0.58 - 1.09 ; P = .16 ) . PSA relapse ( median PSA relapse-free survival , 10.3 years for radiotherapy vs 3.1 years for observation ; HR , 0.43 ; 95 % CI , 0.31 - 0.58 ; P<.001 ) and disease recurrence ( median recurrence-free survival , 13.8 years for radiotherapy vs 9.9 years for observation ; HR , 0.62 ; 95 % CI , 0.46 - 0.82 ; P = .001 ) were both significantly reduced with radiotherapy . Adverse effects were more common with radiotherapy vs observation ( 23.8 % vs 11.9 % ) , including rectal complications ( 3.3 % vs 0 % ) , urethral strictures ( 17.8 % vs 9.5 % ) , and total urinary incontinence ( 6.5 % vs 2.8 % ) . CONCLUSIONS In men who had undergone radical prostatectomy for pathologically advanced prostate cancer , adjuvant radiotherapy result ed in significantly reduced risk of PSA relapse and disease recurrence , although the improvements in metastasis-free survival and overall survival were not statistically significant . Trial Registration clinical trials.gov Identifier : NCT00394511 BACKGROUND In 2002 , we reported the initial results of a trial comparing radical prostatectomy with watchful waiting in the management of early prostate cancer . After three more years of follow-up , we report estimated 10-year results . METHODS From October 1989 through February 1999 , 695 men with early prostate cancer ( mean age , 64.7 years ) were r and omly assigned to radical prostatectomy ( 347 men ) or watchful waiting ( 348 men ) . The follow-up was complete through 2003 , with blinded evaluation of the causes of death . The primary end point was death due to prostate cancer ; the secondary end points were death from any cause , metastasis , and local progression . RESULTS During a median of 8.2 years of follow-up , 83 men in the surgery group and 106 men in the watchful-waiting group died ( P=0.04 ) . In 30 of the 347 men assigned to surgery ( 8.6 percent ) and 50 of the 348 men assigned to watchful waiting ( 14.4 percent ) , death was due to prostate cancer . The difference in the cumulative incidence of death due to prostate cancer increased from 2.0 percentage points after 5 years to 5.3 percentage points after 10 years , for a relative risk of 0.56 ( 95 percent confidence interval , 0.36 to 0.88 ; P=0.01 by Gray 's test ) . For distant metastasis , the corresponding increase was from 1.7 to 10.2 percentage points , for a relative risk in the surgery group of 0.60 ( 95 percent confidence interval , 0.42 to 0.86 ; P=0.004 by Gray 's test ) , and for local progression , the increase was from 19.1 to 25.1 percentage points , for a relative risk of 0.33 ( 95 percent confidence interval , 0.25 to 0.44 ; P<0.001 by Gray 's test ) . CONCLUSIONS Radical prostatectomy reduces disease-specific mortality , overall mortality , and the risks of metastasis and local progression . The absolute reduction in the risk of death after 10 years is small , but the reductions in the risks of metastasis and local tumor progression are substantial PURPOSE The r and omized controlled European Organisation for Research and Treatment of Cancer ( EORTC ) trial 22911 studied the effect of radiotherapy after prostatectomy in patients with adverse risk factors . Review pathology data of specimens from participants in this trial were analyzed to identify which factors predict increased benefit from adjuvant radiotherapy . PATIENTS AND METHODS After prostatectomy , 1,005 patients with stage pT3 and /or positive surgical margins were r and omly assigned to a wait- and -see ( n = 503 ) and an adjuvant radiotherapy ( 60 Gy conventional irradiation ) arm ( n = 502 ) . Pathologic review data were available for 552 patients from 11 participating centers . The interaction between the review pathology characteristics and treatment benefit was assessed by log-rank test for heterogeneity ( P < .05 ) . RESULTS Margin status assessed by review pathology was the strongest predictor of prolonged biochemical disease-free survival with immediate postoperative radiotherapy ( heterogeneity , P < .01 ) : by year 5 , immediate postoperative irradiation could prevent 291 events/1,000 patients with positive margins versus 88 events/1,000 patients with negative margins . The hazard ratio for immediate irradiation was 0.38 ( 95 % CI , 0.26 to 0.54 ) and 0.88 ( 95 % CI , 0.53 to 1.46 ) in the groups with positive and negative margins , respectively . We could not identify a significant impact of the positive margin localization . CONCLUSION Provided careful pathology of the prostatectomy is performed , our results suggest that immediate postoperative radiotherapy might not be recommended for prostate cancer patients with negative surgical margins . These findings require validation on an independent data set |
2,245 | 20,030,702 | No evidence was found for the effectiveness of communication training on patient distress outcomes .
We concluded that the current review reveals inconclusive evidence to prove the effectiveness of communication training on patient satisfaction and patient distress . | The objective of this review was to determine whether communication training for healthcare professionals ( HCP ) , including nurses and medical doctors , in cancer care improves patient outcomes . | We investigated whether a short course in communication skills for physicians would improve the quality of informed consent in a r and omized clinical adjuvant trial on breast cancer . In this prospect i ve , case-controlled intervention study , physicians and research nurses who introduced the cancer treatment trial to patients at three of the participating hospitals first attended a one-day communication skills course . The quality of informed consent was then evaluated by addressing a st and ardized question naire , QuIC , to trial patients at the three intervention hospitals and at control hospitals . Response rate was 90.0 % ( n = 288 ) . Of the patients treated by the intervention group , 73 % were very satisfied with the information received compared with 56 % of those of the control group ( p = 0.003 ) . The patients of the intervention group considered the time given for making their decision sufficient more often than those of the controls ( 98 % vs. 90 % , p=0.004 ) . The patients of the intervention group recalled more often than those of the controls that the physician had also offered other therapeutic options than the trial treatment ( 91 % vs. 97 % , p=0.032 ) . They also understood the main aim of the study better than the patients of the controls ( 89 % vs. 78 % , p=0.030 ) . In conclusion , a short communication skills course for the trial physicians and nurses improved the quality of informed consent and patient satisfaction in the trial There is today a wide consensus regarding the need to improve communication skills ( CS ) of health-care professionals ( HCPs ) dealing with cancer patients . Psychological training programs ( PTPs ) may be useful to acquire the needed CS . Testing the efficacy of PTP will allow to define their optimal content . The present study was design ed to assess the impact of a PTP on HCP stress , attitudes and CS , and on HCP and patients ' satisfaction with HCP communication skills in a r and omised study . A total of 115 oncology nurses were r and omly assigned to a 105-h PTP or to a waiting list . Stress was assessed with the Nursing Stress Scale , attitudes with a Semantic Differential Question naire , CS used during one simulated and one actual patient interview with the Cancer Research Campaign Workshop Evaluation Manual , and satisfaction with the nurses ' CS with a question naire completed by the patients and the nurses . Trained ( TG ) and control ( CG ) groups were compared at baseline , after 3 months ( just following training for TG ) and after 6 months ( 3 months after the end of training for TG ) . Compared to controls , trained nurses reported positive changes on their stress levels ( P⩽0.05 ) and on their attitudes ( P⩽0.05 ) . Positive training effects were found on CS used during the simulated interview : a significant increase in facilitative behaviours ( open questions : P⩽0.001 ; evaluative functions : P⩽0.05 ) and a significant decrease in inhibitory behaviours ( inappropriate information : P⩽0.01 ; false reassurance : P⩽0.05 ) . Less positive training effects were found regarding interviews with a cancer patient : a significant increase in educated guesses ( P⩽0.001 ) was noticed . No training effect was observed on nurses ' satisfaction levels , but a positive training effect was found on patients ' satisfaction levels ( P⩽0.01 ) . Although results outline PTP efficacy , they indicate the need to design PTP , amplifying the transfer of learned CS to clinical practice PURPOSE We wanted to assess the effectiveness of intensive education for physicians compared with a traditional session on communicating with breast cancer patients . METHODS A r and omized controlled trial was conducted in practice s in London , Hamilton , and Toronto , Canada , with 17 family physicians , 16 surgeons , and 18 oncologists , and with 102 patients of the surgeons and oncologists . Doctors were r and omized to 1 of 2 continuing education approaches : a traditional 2-hour version ( control group ) , or a new 6-hour intensive version including exploring the patients ’ perspectives and review ing videotapes and receiving feedback ( intervention group ) . Communication behavior of the physicians was measured objective ly both before and after the intervention . As well , 4 postintervention patient outcomes were measured , by design only for surgeons and oncologists : patient-centerdness of the visit , satisfaction , psychological distress , and feeling better . RESULTS No significant differences were found on the communication score of the intervention vs the control physicians when controlling for preintervention communication scores . Intervention family physicians , however , had significantly higher communication subscores than control family physicians . Also , patients of the intervention surgeons and oncologists were significantly more satisfied ( scores of 82.06 vs 77.78 , P = .03 ) and felt better ( 88.2 % vs 70.6 % , P=.02 ) than patients of the control surgeons and oncologists when controlling for covariates and adjusting for clustering within doctor . CONCLUSIONS The continuing medical education intervention was effective in terms of some but not all physician and patient outcomes The efficacy of a communication skills training programme was shown through a r and omised trial . Oncologists ( N=160 ) from 34 cancer centres were allocated to written feedback plus course ; course alone ; written feedback alone or control . Each clinician had 6 – 10 interviews with patients videotaped at baseline and 3 months postintervention . Analysis of videotapes revealed improvements in the communication skills of clinicians r and omised to training ( n=80 ) compared with others ( n=80 ) . A 12-month follow-up assessment is reported here . Robust Poisson conditional analyses of counts of changes in communication behaviours revealed no demonstrable attrition in those who had shown improvement previously , including fewer leading questions , appropriate use of focused and open-ended questions and responses to patient cues . Additional skills , not apparent at 3 months , were now evident ; the estimated effect sizes corresponded to 81 % fewer interruptions ( P=0.001 ) and increased summarising of information to 38 % ( P=0.038 ) . However , expressions of empathy ( 54 % , P=0.001 ) declined . The overall results show that 12 – 15 months postintervention , clinicians had integrated key communication skills into clinical practice and were applying others . This is the first RCT to show an enduring effect of communication skills training with transfer into the clinic BACKGROUND No study has yet assessed the impact of physicians ' skills acquisition after a communication skills training programme on the evolution of patients ' anxiety following a medical consultation . This study aim ed to compare the impact , on patients ' anxiety , of a basic communication skills training programme ( BT ) and the same programme consoli date d by consolidation workshops ( CW ) , and to investigate physicians ' communication variables associated with patients ' anxiety . PATIENTS AND METHODS Physicians , after attending the BT , were r and omly assigned to CW or to a waiting list . The control group was not a non-intervention group . Consultations with a cancer patient were recorded . Patients ' anxiety was assessed with the State Trait Anxiety Inventory before and after a consultation . Communication skills were analysed according to the Cancer Research Campaign Workshop Evaluation Manual . RESULTS No statistically significant change over time and between groups was observed . Mixed-effects modelling showed that a decrease in patients ' anxiety was linked with screening questions ( P = 0.045 ) , physicians ' satisfaction about support given ( P = 0.004 ) and with patients ' distress ( P < 0.001 ) . An increase in anxiety was linked with breaking bad news ( P = 0.050 ) and with supportive skills ( P = 0.013 ) . No impact of the training programme was observed . CONCLUSIONS This study shows the influence of some communication skills on the evolution of patients ' anxiety . Physicians should be aware of these influences The provision of adequate information in a clear and sensitive manner can improve cancer patients ' experience of care . Satisfaction with the cancer consultation may impact on satisfaction with care in general and adjustment to the disease . This study aims to identify factors that influence patient and clinician satisfaction with the cancer consultation and whether satisfaction can be improved with communication skills training . 160 doctors from 34 UK cancer centres participated . Half were r and omized to attend a communication skills training course . Patient satisfaction data are presented at baseline and following a communication skills course or in the case of the control doctors , three months after baseline . Clinicians also rated their satisfaction with the consultations . Overall patient satisfaction was not related to the speciality , seniority or sex of the clinician or patient , site of primary cancer or type of treatment . Satisfaction was related to patients ' age , psychological morbidity and , most significantly , satisfaction with the length of wait in clinic . Clinician satisfaction was not related to age , sex or cancer site but clinicians were less satisfied following consultations with patients being treated palliatively . Communication skills training had a non-significant positive effect on patient satisfaction . The subtle benefits of improved communication may be overshadowed by practical problems such as waiting too long to see the doctor , which have an adverse effect on satisfaction PURPOSE The purpose of the study was to examine the effect of communication on rectal cancer patients ’ quality of life over four years . Previous studies have either used short follow-up periods or examined only certain aspects of quality of life , such as anxiety and depression . METHODS In a prospect i ve , observational study , rectal cancer patients , recruited by clinicians over a two-year period , were sent question naires over four years . The clinical details of these patients were recorded by the Munich Cancer Registry . The psychological scores from the European Organization for Research and Treatment of Cancer QLQ-C30 and CR38 were the main outcome variables . RESULTS Thirty-nine percent of the sample reported that some aspect of the communication they received was unclear ( incomprehensible or too little ) . More than 60 percent wished to speak more with their physician . Younger patients and those in larger hospitals were more likely to report unclear communication ( P < 0.05 ) . Analyses of covariance , controlled for age , gender , adjuvant therapy , stoma , education , clinic , and comorbidity , demonstrated that role , emotional , and social functioning scores were consistently lower in patients reporting unclear communication . Additionally , these patients experienced more problems sleeping , poorer body image , more financial worries , and a worse future perspective . Repeated measures analyses indicated that sleeping problems and emotional and social functioning difficulties persisted for at least three years . CONCLUSION Reports of unclear communication were associated with poorer quality of life in rectal cancer patients without disease progression The emotional content of health care professionals – cancer patient communication is often considered as poor and has to be improved by an enhancement of health care professionals empathy . One hundred and fifteen oncology nurses participating in a communication skills training workshop were assessed at three different periods . Nurses r and omly allocated to a control group arm ( waiting list ) were assessed a first time and then 3 and 6 months later . Nurses allocated to the training group were assessed before training workshop , just after and 3 months later . Each nurse completed a 20-min clinical and simulated interview . Each interview was analysed by three content analysis systems : two computer-supported content analysis of emotional words , the Harvard Third Psychosocial Dictionary and the Martindale Regressive Imagery Dictionary and an observer rating system of utterances emotional depth level , the Cancer Research Campaign Workshop Evaluation Manual . The results show that in clinical interviews there is an increased use of emotional words by health care professionals right after having been trained ( P=0.056 ) : training group subjects use 4.3 ( std : 3.7 ) emotional words per 1000 used before training workshop , and 7.0 ( std : 5.8 ) right after training workshop and 5.9 ( std : 4.3 ) 3 months later compared to control group subjects which use 4.5 ( std : 4.8 ) emotional words at the first assessment point , 4.3 ( std : 4.1 ) at the second and 4.4 ( std : 3.3 ) at the third . The same trend is noticeable for emotional words used by health care professionals in simulated interviews ( P=0.000 ) . The emotional words registry used by health care professionals however remains stable over time in clinical interviews ( P=0.141 ) and is enlarged in simulated interviews ( P=0.041 ) . This increased use of emotional words by trained health care professionals facilitates cancer patient emotion words expressions compared to untrained health care professionals especially 3 months after training ( P=0.005 ) . This study shows that health care professionals empathy may be improved by communication skills training workshop and that this improvement facilitates cancer patients emotions expression BACKGROUND Doctors ' communication with patients is commonly hampered by lack of training in this core skill . This study aim ed to assess the efficacy of an intensive 3-day training course on communication skills in a r and omised controlled trial with a two-by-two factorial design and several outcomes . METHODS 160 oncologists from 34 UK cancer centres were r and omly allocated to four groups : written feedback followed by course ; course alone ; written feedback alone ; and control . At each of two assessment periods , consultations with six to ten consecutive , consenting patients per doctor were videotaped . 2407 patients participated . Outcome measures included objective and subjective ratings made by research ers , doctors , and patients . The primary outcomes were objective improvements after the intervention in key communication skills . Course content included structured feedback , videotape review of consultations , role-play with simulated patients , interactive group demonstrations , and discussion led by a trained facilitator . FINDINGS In Poisson regression analysis of counts of communication behaviours , course attendance significantly improved key outcomes . The estimated effect sizes corresponded to higher rates of use of focused questions ( difference between course attenders [ n=80 ] and non-attenders [ n=80 ] 34 % , p=0.003 ) , focused and open questions ( 27 % , p=0.005 ) , expressions of empathy ( 69 % , p=0.003 ) , and appropriate responses to patients ' cues ( 38 % , p=0.026 ) , and a 24 % lower rate of use of leading questions ( p=0.11 ) . There was little evidence for the effectiveness of written feedback . INTERPRETATION The communication problems of senior doctors working in cancer medicine are not resolved by time and clinical experience . This trial shows that training courses significantly improve key communication skills . More re sources should be allocated to address doctors ' training needs in this vital area Many intervention studies lack an investigation of the extent to which the intervention was implemented as intended , which makes outcome measures difficult to interpret . The aim of the present study was to gain insight into the implementation process of snoezelen in 24-h dementia care . The intervention in each of six experimental wards comprised training sessions in ' snoezelen for caregivers ' , evaluated using a question naire . To study experience with implementation , the follow-up and general meetings ( 20 in total ) were attended and semi-structured interviews ( six in total ) were conducted . The results indicated that the implementation of snoezelen effected a change from task-oriented care to resident-oriented care . The nursing assistants also experienced changes at the resident level and organisational changes . However , the lack of intervention in the organisational structure and obstructive factors such as under-staffing seemed to get in the way of the integration of multi-sensory stimulation in the daily care in two of the six wards BACKGROUND Patients vary widely in their preferences and capacity for participation in medical decision-making . This study aim ed to document oncologist responses to more extreme presentations and identify helpful and unhelpful strategies for clinicians . PATIENTS AND METHODS A trained actor played the role of a patient with early stage breast cancer who was attending her first consultation with a medical oncologist . She adopted in r and om order two different consultation participation styles : that of a very anxious , active patient , and that of a depressed , passive patient . Medical consultations between the actor and 16 medical oncologists were videotaped and then analysed qualitatively by two trained raters . RESULTS Strategies that facilitated shared decision-making with both patient types and were positively endorsed by the actor/patient included explicit agenda- setting , active listening , checking underst and ing , endorsing question -asking , offering decisional delay , and non-verbal behaviours conveying empathy and warmth . Oncologists successfully negotiated with the active patient to share control of the consultation , and responded to emotional cues from the passive patient . Unhelpful strategies were also identified . CONCLUSIONS Few clinicians receive training in responding to differing communication styles in their patients that could potentially cause conflict and hinder optimal treatment decision-making . This study suggests some useful strategies for oncologists to consider , to widen their behavioural repertoire in the cancer consultation BACKGROUND No study has yet assessed the impact of physicians ' skills acquisition after a communication skills training program on changes in patients ' and relatives ' anxiety following a three-person medical consultation . This study aim ed at comparing , in a r and omized study , the impact , on patients ' and relatives ' anxiety , of a basic communication skills training program and the same program consoli date d by consolidation workshops and at investigating physicians ' communication variables associated with patients ' and relatives ' anxiety . METHODS Consultations with a cancer patient and a relative were recorded and analyzed by the Cancer Research Campaign Workshop Evaluation Manual . Patients ' and relatives ' anxiety were assessed with the State-Trait Anxiety Inventory-State . RESULTS No statistically significant change over time and between groups was observed . Mixed-effects modeling of changes in patients ' and relatives ' anxiety showed that decreases in both patients ' and relatives ' anxiety were linked with patients ' and relatives ' self-reported distress ( p = 0.031 and 0.005 ) , and that increases in both patients ' and relatives ' anxiety were linked with physicians ' breaking bad news ( p = 0.028 and 0.005 ) . CONCLUSION No impact of the training program was observed . Results indicate the need to further study communication skills which may help reduce patients ' and relatives ' anxiety especially when breaking bad news In this paper the effect of a communication training programme on the instrumental and affective communication skills employed by ward nurses during the admittance interview with recently diagnosed cancer patients was investigated . The training focused on teaching nurses skills to discuss and h and le patient emotions . For this purpose , 46 nurses participated in 92 videotaped admittance interviews with simulated patients . The study had a r and omized pre-test-post-test design . Multi-level analysis was used to measure the effects of the training . The results revealed that the trained nurses significantly increased asking open-ended psychosocial questions , which indicates that they were actively exploring patients ' feelings . Furthermore , the patients showed a significant increase in affective communication . In conclusion , the results of this study demonstrate that , although limited , training can induce favourable changes in the communication skills of nurses , and can even affect patient communication . Future studies should focus on the further evaluation of educational programmes to enhance communication skills The importance of good doctor-patient communication is widely recognised . The aims of this study were to evaluate the immediate effects of the participation of patients with cancer on the attitudes and skills of undergraduate medical students receiving an interview skills training programme , and to assess the effects of the participation of patients with cancer on the attitudes and interview performance of students 2 years later . It was hypothesised that the participation of cancer patients would have specific beneficial effects on attitudes and interview performance . Before participating in a 6-session interview methods course in third year , students were r and omised to be taught with patients who had cancer ( experimental group ) or with patients with other diagnoses ( control group ) . Before and after participating in the course , 233 students ( 94 % response rate ) completed an Attitudes Question naire . When they reached their fifth year , 54 students again completed the Attitudes Question naire and , in addition , made a video recording of an interview with a patient who had gynaecological cancer . These recordings were rated independently by two research ers using the Interview Rating Instrument . Immediately after the course , a number of differences were found between the two groups . For example , students in the experimental group were more likely to consider the ability to listen an extremely important characteristic of hospital doctors and to consider more strongly that trust is an essential part of the doctor-patient relationship . 2 years after the course , the ability of hospital doctors to communicate with patients , and the need for clinical decisions to reflect patients ' wishes , were considered to be more important by students in the experimental group , although even 96 % of controls felt both these issues were very or extremely important . As hypothesised , the experimental group had better ratings in terms of responding empathically , showing regard and concern for the patient , and assessing the impact of the symptoms on the patient 's life . The participation of patients with cancer has beneficial and enduring effects on the attitudes and interview performance of medical undergraduates . Medical schools should consider how best patients with cancer can make an important contribution to communication skills training OBJECTIVE To identify health care aspects of inadequate quality in rheumatoid arthritis ( RA ) care from the perspective of patients , and to study to what extent patients ' perspectives on quality of care are associated with patient characteristics . DESIGN Cross-sectional question naire survey performed in 1999 . SETTING Secondary and tertiary rheumatology outpatient clinics . STUDY PARTICIPANTS A r and om sample ( n = 683 ) of patients diagnosed with rheumatoid arthritis according to the 1987 revised American College of Rheumatology criteria . Patients varied widely with respect to age ( mean 61.5 years ) and disease duration ( mean 10.7 years ) . MAIN OUTCOME MEASURES Using the method of the QUOTE- question naire , patients ' were asked to rate the importance to them of 29 aspects of care , and to rate the performance of five different health care providers [ i.e. rheumatologist , general practitioner ( GP ) , physiotherapist , home nurse , and formal home help ] relating to these aspects . To identify aspects of inadequate quality , patients ' performance ratings were weighted by importance ratings within each health care service . Inadequate performance on an extremely important aspect was found to be a more serious quality problem than an inadequate performance on an aspect that was less important to patients . Using regression analyses , the association between patients ' quality ratings and patient characteristics was assessed . RESULTS Several aspects of inadequate quality were identified , namely in the field of knowledge of rheumatism and particularly for GPs , physiotherapists , home nurses , and formal home help , and in the field of information on medication and treatment for rheumatologists and GPs . Furthermore , for the majority of the importance and performance ratings , we found no association with patient-related characteristics . CONCLUSIONS Our study demonstrated that the quality of care could be improved further from the perspective of patients . These findings may be used for making health care more responsive to patients ' needs Although st and ardized role-playing sessions ( SRPS ) with simulators are increasingly used to assess health care professionals ' ( HCPs ) communication skills ( CS ) and the effectiveness of training workshops ( TWs ) , nothing has been done to date to define the optimal emotional content of SRPS . Three emotionally different SRPS context s-weakly emotional ( WE- ) , moderately emotional ( ME- ) , and highly emotional (HE-SRPS)-were , therefore , tested in order to assess induced CS and sensitivity to TW-related changes . The study included 25 HCPs . Tape-recorded SRPS , scheduled before and after the TW , were retranscribed , and assessed according to the Cancer Research Campaign Workshop Evaluation Manual ( CRCWEM ) , which provides a rating of form , function and structure for each utterance . Results show that induced CS are different in WE- , ME- , and HE-SRPS , regarding form ( HE-SRPS induced more ' directing ' , ' leading ' or ' multiple ' questions ; WE : 20.7 % ; ME : 19.7 % ; HE : 33.7 % ( p<0.001 ) ) ; function ( HE-SRPS induced more ' inappropriate ' information ; WE : 6 . 5 % ; ME : 8.2 % ; HE : 15.6 % ( p<0.001 ) ) ; and blocking ( HE-SRPS induced more ' blocking ' utterances ; WE : 7.2 % ; ME : 13.8 % ; HE : 30.2 % ( p<0 . 0001 ) ) . Finally , CS changes induced by TWs are the highest in HE-SRPS ( 14.8 % increase of ' open ' questions for the HE- versus 1.0 % for the WE-SRPS ; 11.6 % decrease of ' inappropriate ' information for the HE- versus 3.3 % for the WE-SRPS ; and 17.5 % decrease of ' blocking ' for the HE- versus 2.6 % for the WE-SRPS ) . In conclusion , SRPS , with a HE content , induce more inappropriate CS . Moreover , they are more sensitive to TW effects . SRPS with a HE content should , thus , be recommended for the assessment of TW effectiveness PURPOSE To measure the psychosocial attitudes and beliefs of physicians working within oncology in the United Kingdom and to examine whether beliefs alter after communication skills training . Additionally , to investigate whether physicians ' attitudes are reflected in communication behaviors with patients during interviews . METHODS Ninety-three physicians completed a 32-item Physician Psychosocial Belief ( PPSB ) question naire at baseline ( T1 ) before r and omization to attendance at a 3-day residential communication skills course ( n = 48 ) or a control group ( n = 45 ) . Three months later ( T2 ) , both groups completed another PPSB and a self- assessment question naire recording perceived changes in communication with patients . At both time points , physicians ' consultations with two consenting patients were videotaped . Communication behaviors were measured using the Medical Interaction Processing System . RESULTS Physicians who attended the course showed significantly improved attitudes and beliefs toward psychosocial issues compared with controls ( P = .002 ) . This improvement was reflected in the analysis of the videotaped recordings of their communication behaviors with patients . Expressions of empathy were more likely for the course group at T2 than the controls ( P = .02 ) , as were open questions ( P = .001 ) , appropriate responses to patient cues ( P = .005 ) , and psychosocial probing ( P = .041 ) . These objective findings were supported by physicians ' self report of changes in communication style during interviews with patients . CONCLUSION Our results show that a communication skills training intervention using behavioral , cognitive , and affective components not only increases potentially beneficial and more effective interviewing styles but can also alter attitudes and beliefs , thus increasing the likelihood that such skills will be used in the clinical setting PURPOSE Although there is wide recognition of the usefulness of improving physicians ' communication skills , no studies have yet assessed the efficacy of post-training consolidation workshops . This study aims to assess the efficacy of six 3-hour consolidation workshops conducted after a 2.5-day basic training program . METHODS Physicians , after attending the basic training program , were r and omly assigned to consolidation workshops or to a waiting list . Training efficacy was assessed through simulated and actual patient interviews that were audiotaped at baseline and after consolidation workshops for the consolidation-workshop group , and approximately 5 months after the end of basic training for the waiting-list group . Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual . Patients ' perceptions of communication skills improvement were assessed using a 14-item question naire . RESULTS Sixty-three physicians completed the training program . Communication skills improved significantly more in the consolidation-workshop group compared with the waiting-list group . In simulated interviews , group-by-time repeated measures analysis of variance showed a significant increase in open and open directive questions ( P = .014 ) and utterances alerting patients to reality ( P = .049 ) , as well as a significant decrease in premature reassurance ( P = .042 ) . In actual patient interviews , results revealed a significant increase in acknowledgements ( P = .022 ) and empathic statements ( P = .009 ) , in educated guesses ( P = .041 ) , and in negotiations ( P = .008 ) . Patients interacting with physicians who benefited from consolidation workshops reported higher scores concerning their physicians ' underst and ing of their disease ( P = .004 ) . CONCLUSION Consolidation workshops further improve a communication skills training program 's efficacy and facilitate the transfer of acquired skills to clinical practice CONTEXT Patients often present clues ( direct or indirect comments about personal aspects of their lives or their emotions ) during conversations with their physicians . These clues represent opportunities for physicians to demonstrate underst and ing and empathy and thus , to deepen the therapeutic alliance that is at the heart of clinical care . A paucity of information exists regarding how physicians address the psychological and social concerns of patients . OBJECTIVES To assess how patients present clues and how physicians respond to these clues in routine primary care and surgical setting s. DESIGN , SETTING , AND PARTICIPANTS Descriptive , qualitative study of 116 r and omly selected routine office visits to 54 primary care physicians and 62 surgeons in community-based practice s in Oregon and Colorado , audiotaped and transcribed in 1994 . MAIN OUTCOME MEASURES Frequency of presentation of clues by patients during office visits , nature ( emotional vs social ) and content of clues , and nature of physician responses to clues , coded as positive or missed opportunity . RESULTS Fifty-two percent and 53 % of the visits in primary care and surgery , respectively , included 1 or more clues . During visits with clues , the mean number of clues per visit was 2.6 in primary care and 1.9 in surgery . Patients initiated approximately 70 % of clues , and physicians initiated 30 % . Seventy-six percent of patient-initiated clues in primary care setting s and 60 % in surgical setting s were emotional in nature . In surgery , 70 % of emotional clues related to patients ' feelings about their biomedical condition , while in primary care , emotional clues more often related to psychological or social concerns ( 80 % ) in patients ' lives . Physicians responded positively to patient emotions in 38 % of cases in surgery and 21 % in primary care , but more frequently they missed opportunities to adequately acknowledge patients ' feelings . Visits with missed opportunities tended to be longer than visits with a positive response . CONCLUSION This study suggests that physicians in both primary care and surgery can improve their ability to respond to patient clues even in the context of their busy clinical practice s. JAMA . 2000;284:1021 - In 1998 , some 179,000 women in the United States were newly diagnosed with breast cancer , and 48,500 women died from it . Early detection by mammography , physical examination , and breast self-examination improves survival rates and can decrease mortality . The clinician 's level of comfort with discussing education and prevention with patients can influence patients ' adherence to preventive measures . Improved clinician-patient interpersonal communication has a demonstrated positive impact on adherence and health outcomes . We developed and pilot tested a core curriculum on breast health aim ed at primary care community physicians and resident house staff . The goal was to improve interpersonal communication between clinician and patient . Two groups of participants attended either a week-long or a 2-week-long training program consisting of four components : a brief demonstration of an interview and breast examination , interviews and breast examinations with a st and ardized patient , and two separate workshops of varying length . This pilot program had a significant impact on clinician behavior and knowledge . We recommend further investigation of this area with larger sample sizes OBJECTIVE Recent studies have recognised that the communication skills learned in the training environment are not always transferred back into the clinical setting . This paper reports a study which investigated the potential of clinical supervision in enhancing the transfer process . METHODS A r and omised controlled trial was conducted involving 61 clinical nurse specialists . All attended a 3-day communication skills training workshop . Twenty-nine were then r and omised to 4 weeks of clinical supervision , aim ed at facilitating transfer of newly acquired skills into practice . Assessment s , using real and simulated patients , were carried out before the course , immediately after the supervision period and 3 months later . Interviews were rated objective ly using the Medical Interview Aural Rating Scale ( MIARS ) to assess nurses ' ability to use key skills , respond to patient cues and identify patient concerns . RESULTS Assessment s with simulated patients showed that the training programme was extremely effective in changing competence in all three key areas . However , only those who experienced supervision showed any evidence of transfer . Improvements were found in the supervised groups ' use of open questions , negotiation and psychological exploration . Whilst neither group facilitated more disclosure of cues or concerns , those in the experimental group responded more effectively to the cues disclosed , reduced their distancing behaviour and increasing their exploration of cues . CONCLUSIONS The study has shown that whilst training enhances skills , without intervention , it may have little effect on clinical practice . The potential role of clinical supervision as one way of enhancing the clinical effectiveness of communication skills training programmes has been demonstrated . PRACTISE IMPLICATION S : This study raises questions about the effectiveness of training programmes which do not incorporate a transfer element , and provides evidence to support the need for clinical supervision for clinical nurse specialist Purpose High- quality palliative care requires physicians who communicate effectively , yet many do not receive adequate training . Leading efforts to demonstrate the effectiveness of such training have involved time-intensive programs that included primarily attending physicians , which have been conducted outside of the United States . The goal was to evaluate the effect of a short course to improve residents ' communication skills delivering bad news and eliciting patients ' preferences for end-of-life care . Method This prospect i ve trial enrolled internal medicine residents at Duke University Medical Center from 1999 to 2001 . The course consisted of small-group teaching with lecture , discussion , and role-play . The outcome measure was observed communication skills delivering bad news and eliciting patients ' preferences for end-of-life treatment , assessed via audio-recorded st and ardized patient encounters before and after receiving the intervention . Results Thirty-seven residents received the intervention and 19 were in the control group . Residents attending the course demonstrated statistically significant increases in their overall skill ratings in the delivery of bad news , with improvement in the specific areas of information giving and responding to emotional cues . Although cumulative scores for discussion s about patient preferences for treatment did not increase , residents demonstrated enhanced specific skills including discussing probability , presenting clinical scenarios , and asking about prior experience with end-of-life decision making . Conclusion A relatively short , intensive course can improve the end-of-life communication skills of U.S. medical residents Clinical trials have come to be regarded as the gold st and ard for treatment evaluation . However , many doctors and their patients experience difficulties when discussing trials , leading to poor accrual to trials and question able quality of informed consent . We have previously developed a typology for ethical communication about Phase II and III clinical trials within four domains : ( a ) shared decision making , ( b ) sequencing information , ( c ) type and clarity of information , and ( d ) disclosure/coercion . The aim of this study was to compare current clinical practice when seeking informed consent with this typology . Fifty-nine consultations in which 10 participating oncologists sought informed consent were audiotaped . Verbatim transcripts were analysed using a coding system to ( a ) identify the presence or absence of aspects of the four domains and ( b ) rate the quality of aspects of two domains : ( i ) shared decision-making and ( ii ) type and clarity of information . Oncologists rarely addressed aspects of shared decision-making , other than offering to delay a treatment decision ( 78 % ) . Moreover , many of these discussion s scored poorly with respect to ideal content . The oncologists were rarely consistent with the sequence of information provision . A general rationale for r and omising was only described in 46 % of consultations . In almost one third of the consultations ( 28.8 % ) doctors made implicit statements favouring one option over another , either st and ard or clinical trial treatment . Doctors complied with some but not other aspects of a st and ard procedure for discussing clinical trials . This reflects the difficulty inherent in seeking ethical informed consent and the need for communication skills training for oncologists INTRODUCTION Clinical trials have come to be regarded as the gold st and ard for treatment evaluation . However , many doctors and their patients experience difficulties when discussing trial participation , leading to poor accrual to trials and question able quality of informed consent . We have previously developed a communication skills training program based on a typology for ethical communication about Phase II and III clinical trials within four categories . The training program consisted of a 1 day experiential workshop that included didactic teaching , exemplary video and role play . The aim of this study was to evaluate the effectiveness of the communication skills training workshop . METHOD Oncologists were recruited from three major teaching hospitals conducting oncology outpatient clinics in three Australian capital cities . Ten oncologists and 90 of their adult cancer patients who were eligible for a Phase II or III clinical trial participated . Ninety informed consent consultations were audiotaped before ( n = 59 ) and after ( n = 31 ) training , and fully transcribed . The presence or absence of each domain component was coded and these were summed within categories . A coding manual was produced which enabled st and ardization of the coding procedure . Patients completed question naires before and after the consultation , and doctors completed a short measure of satisfaction after the consultation . RESULTS Doctors increased their use of some aspects of shared decision-making behavior ( t(87 ) = -1.945 , p = 0.05 ) and described some aspects of essential ethical/ clinical information more commonly . In addition they used less coercive behaviors ( z = -1.976 , p = 0.048 ) . However , they did not provide more clinical information or structure their consultations in the recommended fashion . Patients in the post-training cohort reported more positive attitudes to clinical trials , but other outcomes were not affected by the intervention . CONCLUSIONS This short training programme demonstrated limited success in improving the oncologist 's communication skills when gaining informed consent . A larger r and omized controlled trial of extended training is now underway A prospect i ve study of the impact of training 41 hospice nurses in assessment skills was used to test hypotheses that blocking behaviours would be used more when patients disclosed feelings and used less when nurses perceived that they had satisfactory professional support . Each nurse was asked to assess a patient 's current problems before and after feedback training and 8 months later . Audiotape recordings of these interviews were rated by trained raters . They determined the frequency of nurses ' responses which had the function of blocking patient disclosure and the emotional level of patient disclosure . Before each patient assessment each nurse was interviewed and question naires administered to measure her perceptions of the support she received . Blocking behaviours were most evident when patients disclosed their feelings ( Kendalls r = 0.36 , P < 0.001 ) . In interviews containing most patient disclosure of feeling , blocking was significantly less ( r = -0.24 , P < 0.5 ) when the nurse felt that practical help would be available if needed and when the nurse felt that her direct supervisor was concerned about the nurse 's own welfare ( r = -0.37 , P < 0.005 ) A course in psychosocial oncology for nurses was developed and evaluated within the framework of a prospect i ve r and omised study . Six nurses participated . Areas covered were basic techniques for assessment of psychosocial problems , for relieving anxiety and depression , solving problems in conjunction with treatment and disease , and improving communication . Participants met for four 3h weekly lessons . Between meetings , they met to train assessment and techniques . Follow-up discussion s were held at termination and 5 months later . Participants reported that the new knowledge and skills had made them feel more confident when h and ling patients ' psychosocial situation . However , treatment of psychological problems did not prove to be a predominant aspect of their patient work . The evaluation of the course suggests that participants improved their skills for assessment of patient problems and , therefore , felt more confident when h and ling psychosocial issues Effective communication is widely regarded as a crucial component of patient care that can determine patient satisfaction , compliance and recovery . The plethora of communication skills training programmes available to health professionals is also a testament to the importance of this element of care . However a review of studies evaluating the effectiveness of such training programmes concluded that little behavioural change in health professionals ' communication skills was evident . This paper reports the findings of a programme offered to cancer/palliative care nurses ( n=108 ) via eight condensed three-day workshops at various UK venues . Behavioural change was assessed through evaluation of audiotaped nursing assessment s made pre- and six weeks post-course , scored along nine previously identified key communication areas . Mean overall scores rose by 6 points ( p<0.001 ) to 20 ( out of 27 ) with statistically significant improvements on eight of the nine individual areas . Improvements in subjective levels of confidence in the areas of communication found difficult pre-course were observed immediately post-course ( p<0.001 ) and were still evident six weeks later . Similar improvements immediately post-course for teaching communication skills to colleagues ( p<0.001 ) were further improved six weeks post-course for seven of the eight areas assessed . These results suggest that three-day training courses can lead to clinical ly relevant behavioural change and improvements in perceived confidence in communication and dissemination of skills The usefulness of psychological training programs ( P.T.P. ) in health care setting s devoted to cancer care is beginning to be recognised but their content , form and effectiveness need further investigation . Seventy-two oncology nurses were r and omly assigned to a 24-h P.T.P. or to a waiting list period . Attitudes were assessed by a semantic differential question naire , occupational stress was assessed by the Nursing Stress Scale and communication skills were assessed by st and ardised videotaped role-playing exercises . These were used to compare trained ( T.S. ) and control subjects ( C.S. ) . The results show a significant training effect on attitudes ( P = 0.05 ) , especially on those related to self concept ( P = 0.004 ) , and on the level of occupational stress related to inadequate preparation ( P = 0.02 ) . Limited changes were found regarding post-training communication skills . T.S. were significantly more in control of the interview than C.S. ( P = 0.02 ) . The results indicate that 24-h P.T.P. assessed here are effective . The data also demonstrate the need to consoli date the skills acquired by regular post-training sessions |
2,246 | 23,446,890 | The effect of distraction on immediate intake appeared to be independent of dietary restraint .
Evidence indicates that attentive eating is likely to influence food intake , and incorporation of attentive-eating principles into interventions provides a novel approach to aid weight loss and maintenance without the need for conscious calorie counting | BACKGROUND Cognitive processes such as attention and memory may influence food intake , but the degree to which they do is unclear .
OBJECTIVE The objective was to examine whether such cognitive processes influence the amount of food eaten either immediately or in subsequent meals . | To explore the efficacy of a mindfulness-based weight loss intervention for women . Sixty-two women ( ages 19 - 64 ; BMI 22.5 - 52.1 ) who were attempting to lose weight were r and omised to an intervention or control condition . The former were invited to attend four 2-h workshops , the latter were asked to continue with their normal diets . Data were collected at baseline , 4 and 6 months . BMI , physical activity , mental health . At 6 months intervention participants showed significantly greater increases in physical activity compared to controls ( p<.05 ) but no significant differences in weight loss or mental health . However , when intervention participants who reported ' never ' applying the workshop principles at 6 months ( n=7 ) were excluded , results showed both significantly greater increases in physical activity ( 3.1 sessions per week relative to controls , p<.05 ) and significantly greater reductions in BMI ( 0.96 relative to controls , equivalent to 2.32 kg , p<0.5 ) . Reductions in BMI were mediated primarily by reductions in binge eating . Despite its brevity , the intervention was successful at bringing about change . Further refinements should increase its efficacy OBJECTIVE Using self-refilling soup bowls , this study examined whether visual cues related to portion size can influence intake volume without altering either estimated intake or satiation . RESEARCH METHODS AND PROCEDURES Fifty-four participants ( BMI , 17.3 to 36.0 kg/m2 ; 18 to 46 years of age ) were recruited to participate in a study involving soup . The experiment was a between-subject design with two visibility levels : 1 ) an accurate visual cue of a food portion ( normal bowl ) vs. 2 ) a biased visual cue ( self-refilling bowl ) . The soup apparatus was housed in a modified restaurant-style table in which two of four bowls slowly and imperceptibly refilled as their contents were consumed . Outcomes included intake volume , intake estimation , consumption monitoring , and satiety . RESULTS Participants who were unknowingly eating from self-refilling bowls ate more soup [ 14.7+/-8.4 vs. 8.5+/-6.1 oz ; F(1,52)=8.99 ; p<0.01 ] than those eating from normal soup bowls . However , despite consuming 73 % more , they did not believe they had consumed more , nor did they perceive themselves as more sated than those eating from normal bowls . This was unaffected by BMI . DISCUSSION These findings are consistent with the notion that the amount of food on a plate or bowl increases intake because it influences consumption norms and expectations and it lessens one 's reliance on self-monitoring . It seems that people use their eyes to count calories and not their stomachs . The importance of having salient , accurate visual cues can play an important role in the prevention of unintentional overeating How important are visual cues for determining satiation ? To find out , 64 participants were served lunch in a " dark " restaurant where they ate in complete darkness . Half the participants unknowingly received considerably larger " super-size " portions which subsequently led them to eat 36 % more food . Despite this difference , participants ' appetite for dessert and their subjective satiety were largely unaffected by how much they had consumed . Consistent with expectations , participants were also less accurate in estimating their actual consumption quantity than a control group who ate the same meal in the light BACKGROUND Habituation is a form of learning in which repeated exposure to a stimulus leads to a decrease in responding . Eating involves repeated presentation of the same food stimulus in a meal , and habituation is reliably observed within a meal such that faster rates of habituation are associated with less energy intake . It is possible that repeated presentation of the same food over days will lead to long-term habituation , such that subjects habituate to foods repeated over meals . However , no research on long-term habituation to food in humans has been conducted . OBJECTIVE The current study was design ed to assess long-term habituation in 16 obese and 16 nonobese premenopausal women . DESIGN Obese and nonobese women ( aged 20 - 50 y ) were r and omly assigned to receive a macaroni and cheese meal presented 5 times , either daily for 1 wk or once per week for 5 wk . RESULTS In both obese and nonobese women , daily presentation of food result ed in faster habituation and less energy intake than did once-weekly presentation of food . CONCLUSIONS Long-term habituation was observed when the same food was presented at daily meals but not when presented once weekly for 5 wk . These results provide the first evidence of long-term habituation to food in women and show that memory of food over daily meals can increase the rate of habituation and reduce energy intake . This trial was registered at clinical trials.gov as NCT01208870 BACKGROUND The effect of television viewing ( TVV ) with and without advertisements ( ads ) on energy intake is unclear . OBJECTIVE The objectives were to test 1 ) the effect of TVV , with and without ads , on energy intake compared with a control and reading condition and 2 ) the association of distractibility and memory for ads with energy intake and body weight . DESIGN Forty-eight ( 26 female ) adults ( age : 19 - 54 y ) with a body mass index ( in kg/m(2 ) ) of 20 - 35 completed this laboratory-based study . All participants completed 4 buffet-style meals in r and om order in the following conditions : 1 ) control , 2 ) while reading , 3 ) while watching TV with food and nonfood ads ( TV-ads ) , and 4 ) while watching TV with no ads ( TV-no ads ) . Energy intake was quantified by weighing foods . Distractibility and memory for ads in the TV-ads condition were quantified with a norm-referenced test and recognition task , respectively . RESULTS Repeated- measures analysis of variance indicated that energy and macronutrient intake did not differ significantly among the 4 conditions ( P > 0.65 ) . Controlling for sex , memory for ads was associated with body weight ( r = 0.36 , P < 0.05 ) and energy intake but only when viewing TV ( r = 0.39 , P < 0.05 during the TV-no ads condition , and r = 0.29 , P = 0.06 during the TV-ads condition ) . Controlling for sex , distractibility was associated with body weight ( r = 0.36 , P < 0.05 ) but not energy intake . Distractibility , however , accounted for 13 % of the variance in men 's energy intake ( P = 0.11 ) . CONCLUSIONS TVV did not affect energy intake , but individual characteristics ( memory for ads ) were associated with body weight and energy intake in certain conditions . These characteristics should be considered in food intake and intervention studies BACKGROUND Sedentary activities , such as watching television , may disrupt habituation to food cues , thereby increasing motivation to eat and energy intake . OBJECTIVE These experiments were design ed to examine the effect of television watching on habituation of ingestive behavior in children . DESIGN In experiment 1 , all children worked for access to cheeseburgers in trials 1 - 7 ( habituating stimulus ) . In trials 8 - 10 , children in the control group continued to work for cheeseburgers without any dishabituating stimuli , whereas children in the other groups received either a novel food ( French fries ) or television as dishabituating stimuli . Responding for food and amount of food eaten were measured . In experiment 2 , all children had access to 1000 kcal of a preferred snack food . One group watched a continuous television show , and the control groups either watched no television or watched a repeated segment of a television show , which controls for the television stimulus but requires reduced allocation of attention . RESULTS In experiment 1 , both the novel food and the television watching groups reinstated responding for food ( P = 0.009 ) and increased the amount of energy earned ( P = 0.018 ) above the level of the control subjects . In experiment 2 , the continuous television group spent more time eating ( P < 0.0001 ) and consumed more energy than the no television and the repeated segment groups ( P = 0.007 ) . CONCLUSION These experiments show that television watching can dishabituate eating or disrupt the development of habituation , which may provide a mechanism for increased energy intake associated with watching television Long-term behavioral self-regulation is the hallmark of successful weight control . We tested mediators of weight loss and weight loss maintenance in middle-aged women who participated in a r and omized controlled 12-month weight management intervention . Overweight and obese women ( N = 225 , BMI = 31.3 + /- 4.1 kg/m(2 ) ) were r and omly assigned to a control or a 1-year group intervention design ed to promote autonomous self-regulation of body weight . Key exercise , eating behavior , and body image variables were assessed before and after the program , and tested as mediators of weight loss ( 12 months , 86 % retention ) and weight loss maintenance ( 24 months , 81 % retention ) . Multiple mediation was employed and an intention-to-treat analysis conducted . Treatment effects were observed for all putative mediators ( Effect size : 0.32 - 0.79 , P < 0.01 vs. controls ) . Weight change was -7.3 + /- 5.9 % ( 12-month ) and -5.5 + /- 5.0 % ( 24-month ) in the intervention group and -1.7 + /- 5.0 % and -2.2 + /- 7.5 % in controls . Change in most psychosocial variables was associated with 12-month weight change , but only flexible cognitive restraint ( P < 0.01 ) , disinhibition ( P < 0.05 ) , exercise self-efficacy ( P < 0.001 ) , exercise intrinsic motivation ( P < 0.01 ) , and body dissatisfaction ( P < 0.05 ) predicted 24-month weight change . Lower emotional eating , increased flexible cognitive restraint , and fewer exercise barriers mediated 12-month weight loss ( R(2 ) = 0.31 , P < 0.001 ; effect ratio : 0.37 ) , but only flexible restraint and exercise self-efficacy mediated 24-month weight loss ( R(2 ) = 0.17 , P < 0.001 ; effect ratio : 0.89 ) . This is the first study to evaluate self-regulation mediators of weight loss and 2-year weight loss maintenance , in a large sample of overweight women . Results show that lowering emotional eating and adopting a flexible dietary restraint pattern are critical for sustained weight loss . For long-term success , interventions must also be effective in promoting exercise intrinsic motivation and self-efficacy This study compared 2 extended therapy programs for weight management with st and ard behavioral treatment ( BT ) without additional therapy contacts . Participants were 80 obese women who completed 20 weekly group sessions of BT and achieved a mean initial weight loss of 8.74 kg . Participants were r and omly assigned to a no-further-contact condition ( BT only ) or to one of two extended interventions consisting of relapse prevention training ( RPT ) or problem-solving therapy ( PST ) . No significant overall weight-change differences were observed between RPT and BT or between RPT and PST . However , participants who completed the PST intervention had significantly greater long-term weight reductions than BT participants , and a significantly larger percentage of PST participants achieved clinical ly significant losses of 10 % or more in body weight than did BT participants ( 35 % vs. 6 % ) The effect of being reminded of a recent eating episode on subsequent food intake was examined in unrestrained eaters . In Experiment 1 , female participants were exposed to a " lunch cue " ( in which they were asked to think about what they had eaten for lunch ) , or " no cue " ( free thought condition ) , for 5 min prior to eating . Participants ate less following exposure to the " lunch cue " than the " no cue " condition . In Experiment 2 , food intake was measured following exposure to either a " lunch today " cue , " lunch yesterday " cue or " no cue " condition . Intake in the " lunch today " condition was suppressed relative to both the " lunch yesterday " and " no cue " condition . Subjective ratings of hunger , fullness , and desire to eat did not vary as a function of cue type in either Experiment 1 or Experiment 2 . These results are consistent with the suggestion that memory of recent eating is an important cognitive factor influencing food intake Women were divided into those eating at a decelerated or linear rate . Eating rate was then experimentally increased or decreased by asking the women to adapt their rate of eating to curves presented on a computer screen and the effect on food intake and satiety was studied . Decelerated eaters were unable to eat at an increased rate , but ate the same amount of food when eating at a decreased rate as during the control condition . Linear eaters ate more food when eating at an increased rate , but less food when eating at a decreased rate . Decelerated eaters estimated their level of satiety lower when eating at an increased rate but similar to the control condition when eating at a decreased rate . Linear eaters estimated their level of satiety similar to the control level despite eating more food at an increased rate and higher despite eating less food at a decreased rate . The cumulative satiety curve was fitted to a sigmoid curve both in decelerated and linear eater under all conditions . Linear eaters rated their desire to eat and estimated their prospect i ve intake lower than decelerated eaters and scored higher on a scale for restrained eating . It is suggested that linear eaters have difficulty maintaining their intake when eating rate is dissociated from its baseline level and that this puts them at risk of developing disordered eating . It is also suggested that feedback on eating rate can be used as an intervention to treat eating disorders Television viewing ( TVV ) has been linked with obesity , possibly through increased sedentary behavior and /or through increased ingestion during TVV . The proposition that TVV causes increased feeding , however , has not been subjected to experimental verification until recently . Our objective was to determine if the amount eaten of two familiar , palatable , high-density foods ( pizza and macaroni and cheese ) was increased during a 30-min meal when watching TV . In a within-subjects design , one group of undergraduates ( n = 10 ) ate pizza while watching a TV show of their choice for one session and when listening to a symphony during the other session . A second group of undergraduates ( n = 10 ) ate macaroni and cheese ( M&C ) . TVV increased caloric intake by 36 % ( one slice on average ) for pizza and by 71 % for M&C. Eating patterns also differed between conditions . Although the length of time to eat a slice of pizza remained stable between viewing conditions , the amount of time before starting another slice was shorter during TVV . In contrast , M&C was eaten at a faster rate and for a longer period of time during TVV . Thus , watching television increases the amount eaten of high-density , palatable , familiar foods and may constitute one vector contributing to the current obesity crisis This study compared the weight losses of 49 obese women r and omly assigned to a 52-week behavioral program combined with either moderate or severe caloric restriction . Subjects in the balanced deficit diet ( BDD ) condition were prescribed a 1,200-kcal/day diet throughout treatment , and those in the very-low-calorie diet ( VLCD ) condition were given a 420-kcal/day liquid diet for 16 weeks and a 1,200-kcal/day diet thereafter . The VLCD subjects lost significantly more weight than the BDD subjects at all periods through Week 26 , at which time mean losses were 21.45 and 11.86 kg , respectively . VLCD subjects , however , regained weight during the next 26 weeks of weekly therapy and during a 26-week weight maintenance program that provided biweekly meetings . Mean weight losses at the end of the maintenance program were 10.94 and 12.18 kg , respectively . Reports of binge eating declined in both groups , and no relationship was observed between binge eating and weight loss or attrition The objective of the present study , performed under laboratory conditions , was to assess the impact of two non food-related environmental stimuli ( television and auditory stimulus ) on meal intake . Normal weight women ( N = 48 ) ate lunch in the laboratory once a week for four weeks . All lunches were identical and included popular traditional foods , of which participants could eat ad libitum . The first and last lunches were eaten in the absence of the environmental stimuli ( control conditions ) ; in the other two tests , presented in r and om order , subjects ate while either watching television or listening to a recorded story . Energy intakes were determined for each meal , as were ratings of hunger , satiety and meal palatability . Subjects filled out the Three Factor Eating Question naire at the end of the meal series . Meal size was significantly larger in the presence of both environmental stimuli than in both control conditions ( + 11.6 % , 280 kJ , p < 0.01 ) . Television viewing induced a significant stimulation of intake , equal to , but not greater than the effect of the auditory stimulus . Ratings of hunger , satiety , and palatability were not significantly different between conditions , despite the differences in intake . These results suggest that environmental , non food-related stimuli could stimulate intake regardless of hunger-satiety or palatability conditions . Environmental stimulation of eating should be tested in other population s , eg subjects with weight control problems , and other conditions , e.g. free-living At an all-you-can eat buffet in a sports bar , it was tested whether people would eat less if they knew how much they had already eaten . 50 graduate students ( 34 women ; M age = 24.1 yr . ) were seated at 21 tables r and omly assigned to be bussed ( leftover wings removed ) or unbussed ( wings left on table ) . The 31 students at the bussed tables ate more than those at the unbussed tables ( 7 wings vs 5.5 wings ) , with the effect being stronger for men than women . In distracting eating environments , environmental cues may provide an effective means of reducing consumption . Implication s for controlling alcohol intake were also noted |
2,247 | 19,307,799 | There were no significant differences in mortality , malignancy or incidence of infections .
CONCLUSIONS CNI sparing strategies with adjunctive mycophenolate may play an important role in kidney transplant recipients .
Improvements in short-term graft function , and possibly graft survival , are achievable .
Longer term studies are needed to substantiate the short-term benefits , and refining elective CNI elimination protocol s may help to reduce the risk of rejection | BACKGROUND Limiting the exposure of kidney transplant recipients to calcineurin inhibitors ( CNIs ) has potential merit , but there is no clear consensus on the utility of current strategies .
In an attempt to aid clarification , we conducted a systematic review and meta- analysis of r and omized trials that assessed CNI sparing ( minimization or elimination ) with mycophenolate as sole adjunctive immunosuppression . | Long‐term use of calcineurine inhibitors ( CNIs ) may contribute to the development of chronic allograft dysfunction ( CAD ) . We investigate the impact of the introduction of MMF combined with cyclosporine ( CsA ) 50 % dose reduction . An open , r and omized , controlled , multicenter , prospect i ve study was conducted in 103 patients , receiving a CsA‐based therapy with a serum creatinine between 1.7–3.4 mg/dL , more than 1 year after transplantation . They were r and omized to receive MMF with half dose of CsA ( MMF group ) or to continue their maintenance CsA dose ( control group ) . A total of 96 weeks after r and omization , the evolution of renal function assessed by regression line analysis of 1/SeCr improved in the MMF group ( positive slope ) vs. the control group ( negative slope ) , 4.2 × 10−4 vs. −3.0 × 10−4 , respectively ( p < 0.001 ) . Concurrently , the absolute renal function improved significantly in the MMF group . No episode of biopsy‐proven acute rejection occurred . One patient in each group lost his graft because of biopsy‐proven chronic allograft nephropathy . There was a significant decrease of triglycerides level in the MMF group . Anemia and diarrhea were statistically more frequent in the MMF group BACKGROUND Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients . This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens . METHODS We r and omly assigned 1645 renal-transplant recipients to receive st and ard-dose cyclosporine , mycophenolate mofetil , and corticosteroids , or daclizumab induction , mycophenolate mofetil , and corticosteroids in combination with low-dose cyclosporine , low-dose tacrolimus , or low-dose sirolimus . The primary end point was the estimated glomerular filtration rate ( GFR ) , as calculated by the Cockcroft-Gault formula , 12 months after transplantation . Secondary end points included acute rejection and allograft survival . RESULTS The mean calculated GFR was higher in patients receiving low-dose tacrolimus ( 65.4 ml per minute ) than in the other three groups ( range , 56.7 to 59.4 ml per minute ) . The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus ( 12.3 % ) than in those receiving st and ard-dose cyclosporine ( 25.8 % ) , low-dose cyclosporine ( 24.0 % ) , or low-dose sirolimus ( 37.2 % ) . Allograft survival differed significantly among the four groups ( P=0.02 ) and was highest in the low-dose tacrolimus group ( 94.2 % ) , followed by the low-dose cyclosporine group ( 93.1 % ) , the st and ard-dose cyclosporine group ( 89.3 % ) , and the low-dose sirolimus group ( 89.3 % ) . Serious adverse events were more common in the low-dose sirolimus group than in the other groups ( 53.2 % vs. a range of 43.4 to 44.3 % ) , although a similar proportion of patients in each group had at least one adverse event during treatment ( 86.3 to 90.5 % ) . CONCLUSIONS A regimen of daclizumab , mycophenolate mofetil , and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function , allograft survival , and acute rejection rates , as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with st and ard-dose cyclosporine without induction . ( Clinical Trials.gov number , NCT00231764 [ Clinical Trials.gov ] . ) Background . This study determined whether cyclosporine A (CsA)-treated renal allograft recipients with deteriorating renal function ( “ creeping creatinine ” ) secondary to chronic allograft nephropathy ( CAN ) benefit from the addition of mycophenolate mofetil ( MMF ) to their immunosuppressive regimen , followed by withdrawal of CsA. Methods . In a controlled , open , multicenter study , CsA-treated renal allograft recipients with progressively deteriorating renal function were r and omized to have their CsA discontinued with the concomitant addition of MMF to their regimen ( group A ) or to continue treatment with CsA ( group B ) . The primary endpoint was the response rate over the 6-month period after withdrawal of CsA in group A or the equivalent time in group B. Response was defined as a stabilization or reduction of serum creatinine ( SCr ) , as evidence d by a flattening or positive slope of the 1/SCr plot and no graft loss . Secondary endpoints included the incidence of acute rejection , graft and patient survival , and changes in selected metabolic parameters . Results . The response rate in the primary intent-to-treat population ( n=122 ) was 58 % ( 36/62 ) in group A versus 32 % ( 19/60 ) in group B ( P=0.0060 ) . The corresponding percentages of responders in the per- protocol population ( n=107 ) were 60 % ( 36/60 ) and 26 % ( 12/47 ) , respectively ( P=0.0008 ) . There were no acute rejections in group A during the study period . Patients in this group also experienced a significant decrease in total cholesterol . Conclusions . In patients with progressively deteriorating renal function secondary to CAN , addition of MMF followed by withdrawal of CsA results in a significant improvement in transplant function without the risk of acute rejection Background . Long-term maintenance immunosuppression with cyclosporine ( CsA ) is associated with chronic transplant nephropathy and adverse effects on blood pressure and lipid profile . Several nonr and omized studies suggest that CsA might safely be withdrawn from immunosuppressive regimens containing mycophenolate mofetil ( MMF ; CellCept ) . Methods . A r and omized , controlled study with 187 patients enrolled from 21 centers was conducted to compare CsA withdrawal with ongoing CsA therapy in stable renal transplant recipients receiving a triple-drug immunosuppressive regimen of MMF ( 2 g/day ) , CsA ( Neoral ) , and corticosteroids . The primary endpoint was creatinine clearance at 6 months after complete withdrawal . Results . In the intent-to-treat population , CsA withdrawal was associated with lower total cholesterol and low-density lipoprotein cholesterol ( −0.3 mmol/L , P = 0.02 ; −0.4 mmol/L , P = 0.015 ) . There was a trend toward improved creatinine clearance ( 4.5 mL/min , P = 0.16 ) and serum creatinine ( −1 vs. + 4 & mgr;mol/L , P = 0.34 ) . In the per- protocol population , which excluded patients with acute rejections , the improvements in creatinine clearance and serum creatinine were statistically significant ( 7.5 mL/min , P = 0.02 ; −11 vs. + 4 & mgr;mol/L , P = 0.0003 ) . Reversible acute rejections , the majority of which were mild , occurred in nine CsA withdrawal versus two CsA continuation patients ( 10.6 % vs. 2.4 % of each group , P = 0.03 ) , with no graft loss . Conclusion . Withdrawal of CsA from an MMF-containing triple-drug immunosuppressive regimen improves renal function and lipid profile at the cost of a modest increase in acute rejections , without graft loss Maintenance immunosuppression with cyclosporine ( CsA ) is associated with nephrotoxicity , hyperlipidemia , and hypertension . This long-term study ( core study + 4 yr of follow-up ) investigated the long-term efficacy and safety of CsA withdrawal from a mycophenolate mofetil (MMF)-based regimen . Seventy-seven patients were maintained on CsA , MMF , and steroids ( CsA-MMF group ) , and 74 were given a CsA-free regimen of MMF and steroids ( MMF group ) . Serum creatinine and creatinine clearance were measured at 6-month intervals . Patient and graft survival , acute rejection episodes , malignancies , BP , and lipid profile were also recorded . At 5 yr , patient and graft survival was 93 and 88 % , respectively , for the MMF group and 95 and 92 % , respectively , for the CsA-MMF group . During follow-up , seven MMF patients experienced acute rejection episodes compared with one CsA-MMF patient ( P = 0.0283 ) . Nine grafts were lost to chronic rejection in the MMF group versus three in the CsA-MMF group . No demographic or immunologic characteristics were associated with acute or chronic rejection in the MMF group , but the doses of both MMF and steroids decreased significantly between 1 and 5 yr . The MMF group showed a trend toward improved creatinine clearance ( 67.4 versus 61.7 ml/min ; P = 0.0500 ) . Withdrawal of CsA from an MMF-containing immunosuppressive regimen result ed in an increased risk for acute rejection episodes and graft loss as a result of rejection throughout the 5-yr study period . The creatinine clearance-confirmed improvement in renal function observed at year 1 was maintained at 5 yr BP and cholesterol levels were well controlled in both groups BACKGROUND This study was conducted to assess the effect of immunosuppression conversion on progression of chronic allograft nephropathy ( CAN ) . METHODS Forty-two cyclosporin-treated renal transplant recipients were studied . Patients were included if they had a negatively sloping reciprocal of creatinine vs time ( ROCT ) plot for > 6 months and biopsy-proven CAN . Patients were excluded if they had previously been treated with tacrolimus/mycophenolate mofetil ( MMF ) or their serum creatinine was > 400 micromol/l . Subjects were r and omly treated with either : ( A ) MMF/reduced dose cyclosporin [ MMF for azathioprine 0.5 - 1.0 g bd ; cyclosporin trough level ( C(0 ) ) : 75 - 100 ng/ml ] ; ( B ) tacrolimus for cyclosporin ( C(0 ) : 5 - 10 ng/ml ) ; or ( C ) continuation of st and ard therapy . Glomerular filtration rate ( GFR ) was measured at baseline and after 6 months . RESULTS Two patients started dialysis within 6 months ( one each from groups A and B ) . One patient in group A was intolerant of MMF , six others reported gastrointestinal symptoms and three developed anaemia . Cyclosporin dose was reduced by 24 % [ interquartile range ( IQR ) : 14 - 27 % ] in group A [ end-of- study C(0 ) : 99 ng/ml ( IQR : 90 - 113 ng/ml ) ] . In group B , the end-of- study tacrolimus C(0 ) was 7 ng/ml ( 5 - 9 ng/ml ) . The end-of- study cyclosporin C(0 ) in group C was 163 ng/ml ( 145 - 215 ng/ml ) . Comparison of ROCT slopes before and after intervention revealed a treatment advantage for group A ( P<0.05 ) . The GFR analysis was supportive ( P = 0.05 ) . When patients with GFR < 20 ml/min/1.73 m(2 ) at enrollment were excluded from the analysis , the treatment advantage for group A reached statistical significance ( n = 27 , P<0.05 ) . CONCLUSIONS MMF/reduced dose cyclosporin is superior to tacrolimus-for-cyclosporin and st and ard dose cyclosporin in patients with CAN , at least in the short term . The cyclosporin dose reduction component is likely to be of particular importance . Other findings suggest that early intervention is beneficial Background . We report the two-year follow-up of a trial comparing the three-month postgraft discontinuation of either cyclosporine ( CsA ) or mycophenolate mofetil ( MMF ) from a triple-drug regimen after de novo renal transplantation . Methods . One hundred and eight patients were enrolled in this study and r and omized to be withdrawn from CsA ( MMF group , n=54 ) or MMF ( CsA group , n=54 ) . Results . Despite an increased risk of acute rejection and a lower , but nonsignificant , two-year graft survival , CsA withdrawal induced a sustained improvement of the renal function . At one year , the chronic allograft damage index was similar in both the MMF and CsA groups . However , CsA elimination result ed in a higher incidence of C4d deposits , irrespective of the occurrence of a prior acute rejection . While this finding could suggest a risk of chronic rejection in the MMF group , the outcome did not appear to be related to the C4d status . Moreover , logistic regression analysis showed that only two factors , acute rejection and the one-year glomerular filtration rate level , were predictive of a significant decline of the renal function at two years . Conclusions . These results point out the need to secure the minimization of the calcineurin inhibitors after renal transplantation , in order to reduce the risk of acute rejection in these patients , because this strategy allows the improvement of the one-year renal function which is predictive of a chronic allograft dysfunction Uncertainty exists regarding the necessity of continuing triple therapy consisting of mycophenolate mofetil ( MMF ) , cyclosporine ( CsA ) , and prednisone ( Pred ) after kidney transplantation ( RTx ) . At 6 mo after RTx , 212 patients were r and omized to stop CsA ( n = 63 ) , stop Pred ( n = 76 ) , or continue triple drug therapy ( n = 73 ) . The MMF dose was 1000 mg twice daily , target CsA trough levels were 150 ng/ml , and Pred dose was 0.10 mg/kg per d. Follow-up was until 24 mo after RTx . Biopsy-proven acute rejection occurred in 14 ( 22 % ) of 63 patients after CsA withdrawal compared with 3 ( 4 % ) of 76 in the Pred withdrawal group ( P = 0.001 ) and 1 ( 1.4 % ) of 73 in the control group ( P = 0.0001 ) . Biopsy-proven chronic rejection was present in one patient in the control group , in nine patients after CsA withdrawal ( P = 0.006 versus control group ) ; and in four patients after discontinuation of Pred ( NS ) . Graft loss occurred in two versus one patient after CsA or Pred withdrawal , respectively , and in two patients in the control group ( NS ) . Patients who successfully withdrew CsA had a significantly lower serum creatinine during follow-up . Pred withdrawal result ed in a reduction in mean arterial pressure , and the total cholesterol/HDL ratio increased . In conclusion , rapid CsA withdrawal at 6 mo after RTx results in a significantly increased incidence of biopsy-proven acute and chronic rejection . Pred withdrawal was safe and result ed in a reduction in mean arterial pressure . However , patient and graft survival and renal function 2 yr after RTx were not different among groups Background . Calcineurin inhibitor (CNI)–free regimens posttransplantation have been cl aim ed to conserve graft function in addition to reduce the risk factors for cardiovascular and malignant disease in renal transplant recipients . Methods . The primary aim of this prospect i ve , open-label , r and omized , parallel-group , single-center study was to compare the effect of complete CNI-avoidance posttransplant ( daclizumab + mycophenolate mofetil + prednisolone : Dac-group , n=27 ) with the st and ard CNI-based immunosuppressive protocol at our transplant unit ( cyclosporine A + mycophenolate mofetil + prednisolone : CsA-group , n=27 ) on renal function ( glomerular filtration rate [ GFR ] determined as plasma clearance of 51Cr-EDTA ) in a selected low immunogenic risk population ( DR-matched , PRA-negative de novo cadaveric transplant recipients ) . Results . There were no significant difference in GFR at week 10 ( P=0.61 ) , but GFR was significantly ( P=0.029 ) lower in the Dac-group ( 52±20 ml/min ) at month 12 than in the CsA-group ( 69±29 ml/min ) . One-year patient and graft survival did not differ between the two groups . Overall acute rejection rate was 70.4 % ( 19/27 ) in the Dac-group and 29.6 % ( 8/27 ) in the CsA-group ( P=0.006 ) . Conclusions . The strategy to select DR-matched , PRA-negative de novo cadaveric transplant recipients for a CNI-avoidance protocol was not successful . The incidence of acute rejection was unacceptable high even though anti-CD25 antibody induction as well as initial higher mycophenolate mofetil doses ( 3 g/day ) were applied , and renal function was significantly lower in the CNI-avoidance patients at 1 year . Other strategies need to be examined for avoidance of CNI 's in the early posttransplant period Background . Monitoring cyclosporine microemulsion ( CsA-ME ; Neoral ) exposure 2 hours postdose ( C2 ) has been reported to optimize the efficacy and safety of CsA-ME therapy . The addition of induction therapy to a maintenance regimen including CsA-ME C2 monitoring has not been evaluated . Methods . In all , 123 adult renal transplant recipients were recruited at 14 U.S. centers for this 6-month study . CsA-ME dose was to be titrated to attain C2 targets of 1700 and 1500 ng/ml during posttransplant months 1 and 2 , respectively . After 2 months , patients were r and omized to one of two groups with different , decreasing C2 targets . Basiliximab , mycophenolate mofetil , and corticosteroids completed the study immunosuppression . Results . Of the 119 evaluable patients , 76 % were male , 22 % African American , and 66 % deceased donor recipients . Biopsy-proven acute rejection occurred in 10 patients ( 9.3 % ) ; there were two failed grafts and one death . Serum creatinine and calculated GFR values suggest good renal function , with month 6 medians of 1.5 ng/ml and 67 ml/min/1.73 m2 . Safety and tolerability assessment s revealed no unexpected outcomes . Observed C2 levels were generally lower than protocol targets , particularly in the first weeks posttransplantation . Conclusions . The striking efficacy and outcomes may have been achieved in this study with lower C2 levels of CsA-ME because of the addition of basiliximab induction Although the calcineurin inhibitors ( CNI ) cyclosporine ( CsA ) and tacrolimus are highly effective immunosuppressants , they are associated with serious side effects . There is great interest in immunosuppressive regimens that permit reduction or elimination of CNIs , while maintaining adequate immunosuppression and acceptable acute rejection rates . Patients ( n = 536 ) receiving their first renal allograft were r and omized to one of three immunosuppressant regimens : daclizumab , mycophenolate mofetil ( MMF ) , corticosteroids ( CS ) and low‐dose CsA ( target trough levels of 50–100 ng/mL ) , weaned from month 4 and withdrawn by month 6 ; daclizumab , MMF , CS and low‐dose CsA ; or MMF , CS and st and ard‐dose CsA. Mean GFR 12 months after transplantation ( primary end point ) was not statistically different in the CsA withdrawal and low‐dose CsA groups ( both 50.9 mL/min/1.73 m2 ) vs. the st and ard‐dose CsA group ( 48.6 mL/min/1.73 m2 ) . At 12 months , the incidence of biopsy‐proven acute rejection was significantly higher in the CsA withdrawal group ( 38 % ) vs. the low‐ or st and ard‐dose CsA groups ( 25.4 % and 27.5 % , respectively ; p < 0.05 ) . In summary , a regimen of continuous low‐dose CsA with MMF , CS and daclizumab induction is a clinical ly safe and effective immunosuppressive regimen in renal transplant recipients The aim of this r and omized , open-labeled trial was to compare the incidence of acute rejection after an early ( 3 mo posttransplantation ) withdrawal of cyclosporine ( CsA ) or mycophenolate mofetil ( MMF ) in renal transplantation . Among 218 eligible recipients , 108 nonsensitized , rejection-free patients who were under a triple drug regimen ( CsA-MMF-prednisone ) and had received a first kidney from a deceased donor were enrolled . At 3 mo after graft , they were gradually withdrawn from CsA ( MMF group , n = 54 ) or MMF ( CsA group , n = 54 ) . A graft biopsy and a pharmacokinetic study of CsA and mycophenolic acid were systematic ally performed before the r and omization . At 1 yr , graft and patient survival rates were 100 % in each group . Renal function was improved in the MMF group compared with the CsA group ( Cockcroft calculated clearance 64.7 + /- 18.7 versus 56.5 + /- 18.0 ml/min ; P = 0.023 ) . However , the probability of acute rejection was higher in the MMF group ( 18.5 versus 5.6 % ; P = 0.045 ) . The 10 patients who developed acute rejection after CsA withdrawal had a significantly higher incidence of borderline changes on the r and omization biopsy than the 44 rejection-free patients ( five of 10 versus eight of 44 ; P = 0.034 ) , and they displayed a lower area under the curve of mycophenolic acid ( 43 + /- 9 versus 58 + /- 22 mg/h per L ; P = 0.045 ) . Multivariate analysis confirmed that borderline changes and area under the curve of mycophenolic acid were significant risk factors of acute rejection after CsA discontinuation . It is concluded that a systematic graft biopsy and a pharmacokinetic study of mycophenolic acid are needed to reduce the risk for acute rejection after CsA withdrawal Cyclosporine ( CsA ) is the current primary immunosuppressant for the prevention of renal allograft rejection . Its chronic use is associated with various adverse effects like hypertension , hyperlipidemia , and nephrotoxicity , which in turn may contribute to chronic allograft nephropathy and cardiovascular mortality . This study compares a CsA-free maintenance regimen of mycophenolate mofetil ( MMF ) and corticosteroids with CsA and corticosteroids after early conversion from triple drug therapy . Eighty-four renal transplant recipients who had stable graft function on triple drug therapy with MMF , CsA , and steroids were r and omly assigned to be withdrawn from either CsA ( n = 44 ) or MMF ( n = 40 ) at 3 mo posttransplantation . Kidney function at 1 yr was the primary endpoint . Secondary parameters of efficacy were patient and graft survival , incidence of acute rejection episodes , BP , and lipids . At study entry , the alternative treatment groups were similar with respect to demographics , renal function , dosage of CsA , BP , and concomitant medication . Both the creatinine clearance ( 71.7 versus 60.9 ml/min ) and calculated GFR ( 73.2 versus 61.9 ml/min ) were significantly better in MMF-treated patients at 1 yr . Conversion to MMF was associated with a decline of systolic and diastolic BP ( 128/76 versus 139/82 mmHg ) and with a more favorable lipid profile . There was no difference in patient survival ( 100 % ) and graft survival ( 97.7 % versus 100 % ) . Acute rejection episodes occurred more frequently after withdrawal of CsA ( 11.3 % versus 5.0 % ) , but the difference was NS . Early tapering of CsA can safely be accomplished in renal transplant recipients who are stable on a triple drug regimen with MMF , thereby result ing in improved renal function , a more favorable lipid profile , and beneficial effects on posttransplant hypertension Background . Immunosuppressive regimens based on low doses of cyclosporine A ( CsA ) or tacrolimus ( TAC ) may improve short-term outcome after kidney transplantation ( KT ) , but the optimal immunosuppressive protocol is currently unknown . Methods . This study compared the 24-month efficacy and safety of two immunosuppressive regimens using reduced calcineurin inhibitors ( CNIs ) exposure with st and ard dosage of CsA in 240 patients who were r and omized into three groups : group A ( n=80 ) : Thymoglobulin , CsA ( 4 mg/kg twice daily ) plus azathioprine ( 1.5 mg/kg once daily ) ; group B ( n=80 ) : basiliximab , CsA ( 2 mg/kg/ twice daily ) plus mycophenolate mofetil ( MMF ; 1 g twice daily ) ; and group C ( n=80 ) : basiliximab , TAC ( 0.05 mg/kg/ twice daily ) plus MMF ( 1 g twice daily ) . Steroid administration was identical for all groups . Results . A significantly better creatinine clearance at 12 months , estimated by Cockcroft-Gault ( 57±12 , 65.2±20 , 73.5±27 ml/min , P=0.044 ) , the Jelliffe-2 ( 51.5±16 , 56±19 , 59.4±19 ml/min/1.73 m2 , P=0.041 ) and the Modification of Diet in Renal Disease equations ( 53±17 , 58.5±20 , 61.6±22 ml/min/1.73 m2 , P=0.035 ) , was observed in group C compared with group A. No significant differences were observed between groups B and C. The incidence of biopsy-proven acute rejection was similar between groups ( 15 % , 13.8 % , and 16.3 % ) . In addition , patient and graft survival at 24 months were not different between groups . Adverse effects were similar among groups , but cytomegalovirus infections was significantly higher in group A ( 41 % vs. 20 % vs. 25 % ; P=0.008 ) . Conclusions . Immunosuppressive regimens with reduced CNI exposure provide similar preservation of renal function compared with st and ard dose of CsA after KT and do not lead to underimmunosuppression BACKGROUND The lower limit of exposure to calcineurin inhibitors has not yet been established in de novo renal transplant patients receiving mycophenolic acid therapy with basiliximab . METHODS A 12-month , multicenter , r and omized , open-label trial was carried out in which de novo renal transplant patients received enteric-coated mycophenolate sodium , cyclosporine microemulsion , steroids and basiliximab . Patients were r and omized to receive st and ard-exposure ( n = 45 ) or reduced-exposure ( n = 44 ) cyclosporine , based on differing C2 target ranges , after the first month post-transplant . RESULTS Cyclosporine exposure gradually increased over the first month and was lower than previously recommended . Mean calculated creatinine clearance ( primary end-point ) was similar in the st and ard-exposure and reduced-exposure groups at month 6 ( 55.3+/-3.2 ml/min and 61.5+/-3.7 ml/min respectively , n.s . ) . There were 4 deaths but no death-censored graft losses , result ing in 95.5 % patient and graft survival at one year in both groups . At 6 and 12 months , the incidence of biopsy-proven acute rejection was 17.8 % and 17.8 % in the st and ard-exposure group , and 13.6 % and 15.9 % in the reduced-exposure group . Adverse events were similar between treatment groups . Exploratory analyses could not identify a lower limit for the optimal CsA exposure range , but results suggested that high exposure at one year was associated with deteriorating renal function . CONCLUSIONS These results indicate that enteric-coated mycophenolate sodium with reduced-exposure cyclosporine , steroids and basiliximab induction has an excellent therapeutic effect and is safe in de novo kidney transplant recipients . Lower C2 targets than previously recommended , particularly early post-transplant , do not appear to be associated with compromised efficacy It is unknown whether the addition of mycophenolate mofetil ( MMF ) to cyclosporine ( CsA ) and prednisone after renal transplantation ( RTx ) allows for a reduced dose of CsA , to minimize the incidence of CsA-related side effects and to reduce costs . Therefore , 313 renal allograft recipients were r and omized for treatment with MMF ( 1000 mg twice a day ) , prednisone , and either conventional- or low-dose CsA during the first 3 mo after RTx . The target trough levels were 300 and 150 ng/ml , respectively , during the first 3 mo and 150 ng/ml in both groups thereafter . A total of 313 patients were included : 161 patients received a conventional dose and 152 received a low dose of CsA. During the first 6 mo after RTx , graft failure or patient death occurred in 19 of 161 patients ( 12 % ) in the conventional-dose group and in 11 of 152 patients ( 7 % ) in the low-dose group ( not significant ) . Biopsy-proven acute rejection occurred in 36 of 161 patients ( 22 % ) in the conventional-dose group and in 29 of 152 patients ( 19 % ) in the low-dose group ( not significant ) . The incidence of delayed graft function was similar in both groups ( 31 of 161 [ 19 % ] versus 28 of 152 [ 18 % ] ; not significant ) . Serum creatinine did not differ between the conventional- and the low-dose groups : 151 + /- 56 micromol/L versus 142 + /- 49 micromol/L at 3 mo and 141 + /- 60 micromol/L versus 136 + /- 49 micromol/L at 6 mo . There were no differences between the groups regarding BP , lipid metabolism , and infectious complications . In the low-dose group , an estimated $ 500 per patient was saved on the costs of CsA. In conclusion , the addition of MMF to CsA and prednisone after RTx allows the use of a lower-than-conventional dose of CsA , without increasing the risk of rejection Background . In renal transplantation , the immunosuppressive efficacy of cyclosporine is counterbalanced by its nephrotoxicity . Although cyclosporine improves short-term graft survival , its long-term effects are unclear . Methods . Recipients of first cadaver renal transplants were r and omized into three groups between 1983 and 1986 : azathioprine and prednisolone alone ( AP , n=158 ) , long term cyclosporine alone ( Cy , n=166 ) , and short-term cyclosporine followed by azathioprine and prednisolone ( CyAP , n=165 ) . All groups received methylprednisolone induction . Results . There were no significant differences in patient survival at 15 years ( 48 vs. 56 vs. 51 % , P=0.14 ) , and 15-year graft survival ( censored for death ) in those patients in the CyAP group ( 47 vs. 44 vs. 59 % , P=0.06 ) was not significantly different statistically . When deaths or graft losses before 12 months were censored , the differences in 15-year graft survival between the groups were significant ( 58 % , 51 % , 70 % , P=0.01 ) . The CyAP group also had lower mean serum creatinine at all time points beyond 3 months posttransplant out to 10 years ( 143 vs. 169 vs. 131 μmoles/L , P=0.04 ) . Per protocol analysis , after censoring patients at change in therapy , increased the observed differences in 15-year graft survival between the groups ( 54 vs. 38 vs. 65 % , P=0.01 ) . Conclusion . Survival and function of first cadaveric kidney transplants is improved by use of short-term cyclosporine followed by azathioprine and prednisolone . Long-term cyclosporine use reduces long-term graft survival There has been a need for a prospect i ve , r and omized , controlled trial to determine whether the addition of mycophenolate mofetil ( MMF ) to a calcineurin inhibitor (CNI)‐based regimen or MMF addition followed by CNI withdrawal is an effective treatment for chronic allograft nephropathy ( CAN ) . We conducted the first r and omized , prospect i ve study to compare the introduction of MMF with or without CNI withdrawal in long‐term transplant recipients with histologically proven CAN and deteriorating renal function . The primary endpoint was renal function as indicated by the slope of the inverse serum creatinine vs. time at 32 weeks after r and omization . After an interim analysis found a greater‐than‐expected difference between groups in the slopes of the inverse serum‐creatinine , the study was stopped for ethical reasons . There were 20 patients in the MMF/CNI continuation and 19 patients in the MMF/CNI withdrawal groups ( mean time post‐transplant 7 years ) . Renal function improved in the dual‐therapy compared with the triple‐therapy group ( p = 0.002 ) . Blood pressure decreased in the dual‐therapy group with a significant difference between groups at 35 weeks ( p = 0.04 ) . No acute rejections occurred . Long‐term patients with CAN experience a significant improvement in renal function and blood pressure when CNIs are replaced by MMF Background . The clinical benefits of C2 monitoring of cyclosporine microemulsion have been demonstrated , but C2 targets in renal transplant recipients during the first year require validation . Methods . MO2ART was a prospect i ve , multicenter study of renal transplant recipients managed by C2 monitoring of cyclosporine microemulsion with steroids and mycophenolate mofetil or azathioprine . Patients were r and omized on day 3 to two groups , which were managed from month 3 with higher or lower C2 target ranges ( months 4–6 , 1,000–1,200 ng/mL vs. 800–1,000 ng/mL ; months 7–12 , 800–1,000 ng/mL vs. 600–800 ng/mL , respectively ) . The primary endpoint was the glomerular filtration rate ( GFR ) at month 12 . Results . A total of 296 patients were recruited , of whom 250 remained in the study at 3 months ( higher-C2 , n=131 ; lower-C2 , n=119 ) . GFR at 12 months did not differ between the higher- and lower-C2 groups ( 65±17 mL/min vs. 66±14 mL/min ) . When patients were regrouped according to C2 achieved by months 8 to 12 , those with the lowest C2 ( < 700 ng/mL ) showed the lowest GFR at month 3 and the most pronounced increase in GFR between month 3 and month 12 ( P=0.04 ) . Five episodes of biopsy-proven acute rejection occurred after month 3 ( higher-C2 group , n=2 ; lower-C2 group , n=3 ) . The overall 12-month Kaplan-Meier incidence of biopsy-proven acute rejection was 13.7 % . Patient and graft survival were 93 % and 89 % , respectively , at 12 months . Conclusion . Both C2 target ranges investigated showed excellent and nearly equivalent outcomes at 12 months . The decision to target the higher or lower end of these C2 ranges should be made on an individual basis , taking into account patient and graft characteristics , and co-medication Sub clinical rejection and long-term cyclosporine nephrotoxicity are well-known risk factors of chronic allograft nephropathy . In a prospect i ve study 32 low-risk patients were r and omized to either a reduced CsA dose ( 5 mg/kg/d ) and daclizumab ( group A , n = 16 ) for 7 months posttransplant with subsequent CsA tapering/withdrawal , or to a normal CsA dose ( 10 mg/kg/day ) without daclizumab ( group B , n = 16 ) . Both groups received MMF and prednisone . Protocol biopsies were obtained at engraftment and 3 and 12 months after Tx . The number of rejection episodes was the primary endpoint . The secondary endpoints were : renal function , histological parameters related to CsA , and serum levels of TGF-beta and PDGF-BB . A low incidence of clinical ly suspected rejection episodes was observed ( 19 % in group A and 12.4 % in group B ; P = NS ) . Although protocol biopsies showed 12 sub clinical rejection episodes ( six in group A , six in group B ) , serum creatinine levels were not different between the examined groups at 3 months . However , at 12 months , there was a statistically improved mean creatinine level in group A patients ( 1.2 mg/dL + /- 0.5 in group A vs 1.54 mg/dL in group B ; P < .05 ) . Chronic histopathologic changes were significant for biopsies at 3 and 12 months in both groups compared to the baseline findings for protocol biopsies ( with no differences between groups , or between 3 and 12 months in both groups ) . Serum TGF-beta and PDGF-BB did not differ between the groups . Protocol biopsies may be useful to monitor safety and efficiency of new immunosuppressive protocol s. Immunosuppressive regimens with low CsA doses followed by the drug 's complete withdrawal seem to be efficient and safe in low-risk kidney allograft recipients In a multicentre trial conducted in eight European centres , 232 recipients of cadaveric renal allografts were r and omly allocated to receive either cyclosporin ( 117 patients ) or azathioprine and steroids ( 115 patients ) for immunosuppression . All patients have now been followed up for at least a year . 1-year graft survival was 72 % in the cyclosporin group and 52 % in the control group . 24 of the 84 patients in the cyclosporin group with functioning grafts at 1 year had been changed to azathioprine and steroids , and 1 patient had had prednisolone added to cyclosporin therapy ; the other 59 patients were receiving cyclosporin as their sole immunosuppressive agent . 16 patients on cyclosporin treatment never received steroids . 1-year patient survival was 94 % in the cyclosporin group and 92 % in the control group . There was no difference between the two treatment groups in the prevalence of infection . Lymphoma did not develop in any patient . At 1 year post-transplantation , renal function was poorer in patients on cyclosporin than in those on conventional therapy . Thus the 1-year graft-survival rate is higher with cyclosporin alone as a first-line immunosuppressive agent than with azathioprine and steroids Background . For stable kidney-transplant recipients receiving triple drug therapy with cyclosporine ( CsA ) , prednisone , and mycophenolate mofetil ( MMF ) , it remains unclear what is the optimal dose of CsA beyond the first 6 to 12 months after transplantation . Complete CsA withdrawal has been associated with a significant incidence of acute rejection and , in some studies , chronic rejection as well . Methods . We performed an open , prospect ively r and omized , controlled clinical trial to determine whether CsA could be safely reduced by 50 % . At 1 year or more posttransplant , 64 patients were r and omized to either continue their stable-maintenance CsA dose ( control group , n=32 ) or to lower their CsA dose by 50 % over a 2 month period ( CsA reduction group , n=32 ) . All patients had stable renal-allograft function at the time of enrollment . Results . Within 6 months of r and omization , no episode of acute rejection or graft loss occurred in either group . Patients in the CsA reduction group had a slight but significant increase in their glomerular filtration rate and a trend towards lower serum creatinine . There was also a significant decrease in mean systolic blood pressure , triglycerides , and serum uric acid levels in the CsA reduction group . No significant changes in any of these parameters were observed in the control group . Conclusions . This study suggests that a strategy consisting of a 50 % CsA reduction is safe and is not associated with the increased risk of acute rejection observed in CsA withdrawal studies . It also has the potential to improve short-term allograft function and appears to reduce cardiovascular risk factors such as hypertension and hyperlipidemia Part I of this report appeared in the previous issue ( Br . J. Cancer ( 1976 ) 34,585 ) , and discussed the design of r and omized clinical trials . Part II now describes efficient methods of analysis of r and omized clinical trials in which we wish to compare the duration of survival ( or the time until some other untoward event first occurs ) among different groups of patients . It is intended to enable physicians without statistical training either to analyse such data themselves using life tables , the logrank test and retrospective stratification , or , when such analyses are presented , to appreciate them more critically , but the discussion may also be of interest to statisticians who have not yet specialized in clinical trial analyses |
2,248 | 28,649,802 | Although the investigators of the individual trials concluded that punctal plugs are an effective means for treating dry eye signs and symptoms , the evidence in this systematic review suggests that improvements in symptoms and commonly tested dry eye signs are inconclusive .
Although punctal plugs are believed to be relatively safe , their use is commonly associated with epiphora and , less commonly , with inflammatory conditions such as dacryocystitis | BACKGROUND Dry eye syndrome is a disorder of the tear film that is associated with symptoms of ocular discomfort .
Punctal occlusion is a mechanical treatment that blocks the tear drainage system in order to aid in the preservation of natural tears on the ocular surface .
OBJECTIVES To assess the effects of punctal plugs versus no punctal plugs , different types of punctal plugs , and other interventions for managing dry eye . | We investigated whether canalicular occlusion with a lacrimal plug could increase objective and /or subjective comfort in contact lens ( CL ) wearers ( n = 9 ) with both a history of lens intolerance and relative tear fluid deficiency . A modified Schirmer test ( MST ) was performed with the lids closed and under topical anaesthesia . Patients with values of < 10 mm/5 min were included . The plugs were inserted into the inferior canaliculus of the eye with the lower MST result ; the contralateral eye served as a control . Conjunctival hyperaemia , Rose-Bengal and fluorescein scores , as well as subjective irritation , decreased significantly in plugged eyes at the 1 month follow-up visit but had returned to the pre-operative level at the 3 month visit . Tear fluid plasmin activity was elevated prior to plug insertion . Plasmin activity of the plugged eye was significantly lower at the 1 month visit but neither tear fluid flow ( in the collection capillary ) nor plasmin release showed any changes . The mean MST value improved insignificantly , whereas conjunctival chemosis and limbal hyperaemia showed no improvement at the 1 or 3 month follow-up visits after inferior punctal occlusion . Occlusion of the lower canaliculus with a lacrimal plug seems to induce a relatively short-lasting subjective and objective benefit for CL wearers . Plug escape or adaptive changes in lacrimal fluid secretion/ elimination rate probably took place during the follow-up . The association of increased plasmin activity with tear deficiency might lead to enhanced tissue proteolysis , and thus contribute to CL-related ocular surface changes Purpose : To evaluate the clinical efficacy , retention rates , and complications of SmartPlug insertion compared with silicone punctal plugs in patients with dry eye . Methods : Thirty-six eyes with subjective symptoms of dry eye in addition to a tear film breakup time ( TBUT ) < 5 seconds and evidence of ocular surface damage on rose Bengal or fluorescein staining were included . Treated eyes were r and omized to either a silicone plug or SmartPlug inferior punctal occlusion . Pre- and posttreatment evaluations included subjective symptom scoring , tear meniscus height , TBUT , Schirmer test , fluorescein and rose Bengal staining , and artificial tear use . Results : After a mean follow-up period of 11.2 weeks , both the silicone plug- and SmartPlug-treated eyes showed significant improvement in symptom scoring ( P = 0.002 and P = 0.005 , respectively ) , TBUT ( P = 0.035 and P = 0.009 , respectively ) , and fluorescein ( P = 0.024 and P = 0.016 , respectively ) and rose Bengal ( P = 0.008 and P = 0.046 , respectively ) staining . There was no significant difference in these parameters between the 2 plugs . SmartPlug- , but not the silicone plug-treated eyes showed significant improvement in mean tear meniscus height ( P = 0.037 ) . The use of artificial tear supplements was reduced in 10 ( 55.6 % ) silicone- and 11 ( 61.1 % ) SmartPlug-treated eyes . Minor complications related to plug insertion were experienced in 4 ( 22 % ) silicone- and 2 ( 11 % ) SmartPlug-treated eyes . Spontaneous plug loss occurred with 6 ( 33 % ) silicone plugs . Conclusions : This prospect i ve r and omized trial shows that SmartPlug insertion has equivalent clinical efficacy to the use of conventional silicone plugs . Both SmartPlug and silicone plug use can reduce dependency on tear supplements in > 55 % of patients with dry eye PURPOSE To determine the incidence of dry eye and its risk factors after myopic laser-assisted in situ keratomileusis ( LASIK ) . DESIGN Single-center , prospect i ve r and omized clinical trial of 35 adult patients , aged 24 to 54 years , with myopia undergoing LASIK . METHODS setting and study population : Participants were r and omized to undergo LASIK with a superior or a nasal hinge flap . They were evaluated at 1 week and 1 , 3 , and 6 months after surgery . intervention : Bilateral LASIK with either a superior-hinge Hansatome microkeratome ( n = 17 ) or a nasal-hinge Amadeus microkeratome ( n = 18 ) . main outcome measures : The criterion for dry eye was a total corneal fluorescein staining score > or =3 . Visual acuity , ocular surface parameters , and corneal sensitivity were also analyzed . Cox proportional-hazard regression was used to assess rate ratios ( RRs ) with 95 % confidence intervals . RESULTS The incidence of dry eye in the nasal- and superior-hinge group was eight ( 47.06 % ) of 17 and nine ( 52.94 % ) of 17 at 1 week , seven ( 38.89 % ) of 18 and seven ( 41.18 % ) of 17 at 1 month , four ( 25 % ) of 16 and three ( 17.65 % ) of 17 at 3 months , and two ( 12.50 % ) of 16 and six ( 35.29 % ) of 17 at 6 months , respectively . Dry eye was associated with level of preoperative myopia ( RR 0.88/each diopter , P = .04 ) , laser-calculated ablation depth ( RR 1.01/microm , P = 0.01 ) , and combined ablation depth and flap thickness ( RR 1.01/microm , P = 0.01 ) . CONCLUSIONS Dry eye occurs commonly after LASIK surgery in patients with no history of dry eye . The risk of developing dry eye is correlated with the degree of preoperative myopia and the depth of laser treatment PURPOSE Punctal occlusion using punctal plugs is very effective for the treatment of tear-deficient dry eye . We compared the newly marketed Flex Plug ( FP , Eagle Vision Co. , Ltd. ) and the Eagle Plug ( EP , Eagle Vision Co. , Ltd. ) . SUBJECTS AND METHODS The subjects were patients with severe tear-deficient dry eye who were treated in our dry eye clinic . FP plugs in 8 patients ( 9 eyes ) and EP plugs in 29 patients ( 35 eyes ) were compared during over 4 months of observation with regard to the time until extrusion and the possibility for re-insertion of the plugs . RESULTS During the 4 months after insertion of the plugs , the EP plugs were extruded from 35 of 51 puncta ( 68.6 % ) and the FP plugs were extruded from 4 of 13 puncta ( 30.8 % ) . In the 35 EP extrusions and in the 4 FP extrusions , re-insertion was possible . The time period until extrusion was longer for FP than for EP . In all cases , for both EP and FP , pyogenic granuloma was not observed . DISCUSSION The extrusion rate for EP plugs was much greater than for FP plugs ( 68.6 % to 30.8 % ) . Pyogenic granuloma was not observed in any instance for both types of punctal plugs PURPOSE To study the prevalence of dry eye in a hospital-based population and to evaluate the various risk factors attributable to dry eye . MATERIAL S AND METHODS In this cross-sectional study , 500 patients above 20 years of age were screened r and omly for dry eye . A 13-point question naire , Lissamine Green test , Tear film break-up time ( TBUT ) , Schirmer 's test and presence of str and s/filaments were used to diagnose dry eye . The diagnosis was made when at least three of the tests were positive . The role of air pollution , sunlight , excessive winds , smoking , drugs and refractive status as dry eye risk factors was assessed . RESULTS Ninety-two ( 18.4 % ) patients had dry eye . Dry eye prevalence was maximum in those above 70 years of age ( 36.1 % ) followed by the age group 31 - 40 years ( 20 % ) . It was significantly higher ( P = 0.024 ) in females ( 22.8 % ) than in males ( 14.9 % ) , more common in rural residents ( 19.6 % ) than in urban ( 17.5 % ) and highest among farmers/labourers ( 25.3 % ) . A 2.15 fold increase was found in the odds for dry eye in those exposed to excessive wind , 1.91 fold to sunlight exposure , 1.42 to smoking , 1.38 to air pollution and 2.04 for persons on drugs . Dry eye prevalence was 14 % in emmetropes , 16.8 % in myopes and 22.9 % in hypermetropes . It was 15.6 % in those with corrected and 25.3 % in those with uncorrected refractive errors . CONCLUSION Dry eye is an under-diagnosed ocular disorder . Reduction in the modifiable risk factors of dry eye is essential to reduce its prevalence PURPOSE To evaluate the efficacy of a thermosensitive atelocollagen punctal plug in the treatment of dry eye disease . DESIGN Prospect i ve observational case series . METHODS The thermosensitive atelocollagen punctal plug was warmed at 37 C , 39 C , 41 C , and 43 C to evaluate the appropriate temperature and time for solidification . Dry eye patients were divided into 2 groups according to the preparation method of the atelocollagen punctal plug . In the conventional implantation group , atelocollagen gel was kept at room temperature for 15 minutes before implantation ( 27 eyes of 14 patients ) . In the preheating group , atelocollagen was warmed at 41 C for 8 minutes before implantation ( 23 eyes of 13 dry eye patients ) . Strip meniscometry , vital stainings , tear film break-up time ( BUT ) , and symptom scores were evaluated before and 1 month after plug implantation . RESULTS In vitro experiments revealed that heating at 41 C for 8 minutes was sufficient to solidify the gel . The mean fluorescein score in the conventional implantation group significantly improved after treatment ( before , 3.5 ± 2.3 points ; after , 2.5 ± 0.9 points , P < .05 ) . In the preheating group , the mean fluorescein score ( before , 3.7 ± 1.7 points ; after , 1.5 ± 1.2 points ) , strip meniscometry ( before , 0.6 ± 0.7 mm ; after , 1.1 ± 0.3 mm ) , BUT ( before , 3.2 ± 0.7 seconds ; after , 4.8 ± 1.0 seconds ) , and visual analog scale scores ( before , 6.6 ± 1.5 points ; after , 4.1 ± 0.9 points ) significantly improved after treatment ( P < .05 ) . CONCLUSION The thermosensitive atelocollagen punctal plug was effective for dry eye treatment . The preheating method was found to be useful to strengthen the efficacy of the thermosensitive atelocollagen punctal plug OBJECTIVE To compare the efficacy and safety of cyclosporin A ( [ CsA ] 0.05 % and 0.1 % ophthalmic emulsions ) to vehicle in patients with moderate to severe dry eye disease . DESIGN Multicenter , r and omized , double-masked , parallel-group , 6-month , vehicle-controlled . PARTICIPANTS A total of 877 patients with defined moderate to severe dry eye disease ( 292 to 293 in each treatment group ) . METHODS Two identical clinical trials ; patients were treated twice daily with either CsA , 0.05 % or 0.1 % , or vehicle . The results of these two trials were combined for analysis . MAIN OUTCOME MEASURES EFFICACY corneal and interpalpebral dye staining , Schirmer tear test ( with and without anesthesia ) , tear break-up time , Ocular Surface Disease Index ( OSDI ) , facial expression , patient subjective rating scale , symptoms of dry eye , investigator 's evaluation of global response to treatment , treatment success , and daily use of artificial tears . SAFETY occurrence of adverse events , best-corrected visual acuity , intraocular pressure , biomicroscopy , and blood trough CsA concentrations . RESULTS Treatment with CsA , 0.05 % or 0.1 % , gave significantly ( P < or = 0.05 ) greater improvements than vehicle in two objective signs of dry eye disease ( corneal staining and categorized Schirmer values ) . CsA 0.05 % treatment also gave significantly greater improvements ( P < 0.05 ) in three subjective measures of dry eye disease ( blurred vision , need for concomitant artificial tears , and the physician 's evaluation of global response to treatment ) . There was no dose-response effect . Both CsA treatments exhibited an excellent safety profile , and there were no significant topical or systemic adverse safety findings . CONCLUSIONS The novel ophthalmic formulations CsA 0.05 % and 0.1 % were safe and effective in the treatment of moderate to severe dry eye disease yielding improvements in both objective and subjective measures . Topical CsA represents a new pharmacologically based treatment for dry eye disease that may provide significant patient benefits Purpose . To determine whether canalicular occlusion with collagen and silicone plugs reduces the severity of symptoms in patients with conjunctivitis secondary to dry eye . Methods . This was a prospect i ve , r and omized , double-masked study conducted at a single center in Mexico , in which 61 patients with dry eye/conjunctivitis were assigned to progressive lacrimal occlusion with collagen and silicone plugs or a sham procedural group . Outcome variables included total and individual dry eye and conjunctivitis symptom scores , moisturizing agent usage , best-corrected visual acuity , ocular comfort level , visual performance , corneal/conjunctival fluorescein staining , and incidence of adverse events . Results . Total dry eye and conjunctival symptom scores were reduced by 43.7 and 33.7 % , respectively 2 weeks after occlusion of all four lacrimal canaliculi with collagen plugs , increasing to 77.4 and 72.1 % 2 weeks later following superior canalicular occlusion of both eyes with silicone plugs and inferior placement of collagen plugs . At the 8-week visit ( 4 weeks after silicone plug implantation of the inferior canaliculi of both eyes ) , the reduction in total dry eye and conjunctival symptom scores further increased to 94.2 and 93.0 % , respectively , accompanied by a marked decline in each of the seven individual symptom scores ( dryness , watery eyes , itching , burning , foreign body , fluctuating vision , and light sensitivity ) . In concert with these changes , moisturizing agent usage and corneal/conjunctival fluorescein staining decreased in a progressive fashion over the 8-week study period , and best-corrected visual acuity , ocular comfort , and visual performance improved in the absence of any treatment-related adverse events except for one case of epiphora . The response of patients to lacrimal occlusion can be sharply contrasted with the sham procedure group , which remained relatively unchanged from baseline at each of the study visits . Conclusions . Progressive lacrimal occlusion with collagen and silicone plugs was of clinical benefit to patients with dry eye and conjunctivitis Purpose : The aim of this study was to evaluate the effectiveness of punctal occlusion using hypromellose 2 % in patients with dry eye . Methods : In this prospect i ve , r and omized single-blinded clinical trial , we evaluated 76 eyes of 38 patients ( 36 women and 2 men ) with dry eye secondary to rheumatic diseases . In each patient , the lower lacrimal punctum of 1 eye was occluded using hypromellose 2 % , whereas the contralateral eye underwent a simulation of the procedure ( control group ) . Patients ' eyes were assessed for burning , itching , redness , foreign body sensation , and tearing based on a visual scale question naire ( score , 0–10 ) . We also performed objective tests for evaluation of dry eye using a Schirmer test with anesthesia ( basal tear secretion test ) , the tear film break-up time test , and fluorescein and rose bengal staining tests at 0 , 28 , and 56 days after treatment . Results : Fluorescein and rose bengal staining tests showed that there was a significant reduction in signs after occlusion using hypromellose . The symptoms measured by the visual scale were significantly reduced . The values of the Schirmer test with anesthesia and the break-up time test increased significantly . The effects persisted for up to 8 weeks . There were no dropouts or reported side effects during the 24-month follow-up . Conclusions : Our results suggest that punctal occlusion using hypromellose 2 % is a low-cost and safe additional treatment for dry eye Purpose : A controlled uniocular study to evaluate the short-term efficacy of lacrimal punctum occlusion in the treatment of severe dry eye caused by Sjögren syndrome . Methods : Uniocular punctum occlusion by punctum plug in the upper and lower puncta in 1 eye was performed in 20 patients with severe keratoconjunctivitis Sicca caused by Sjögren syndrome . To overcome possible interindividual variability between patients , the other eye , in the same patient , was not occluded and served as a control eye . The eye to be occluded was r and omly selected . The patients were instructed to continue using their dry eye medications . Tear function tests ( Schirmer test , rose Bengal test , and debris in de cul-de-sac ) were performed in both eyes . Subjective complaints ( discomfort ) were registered for both eyes . All the above-mentioned data were collected before starting the treatment and at least 6 weeks later . The above-mentioned parameters were compared and statistically analyzed in both eyes . Results : Of the 20 patients , 7 patients dropped out . The remaining 13 patients completed the final analysis . In the occluded eye , we found a significant improvement in both the subjective complaints and the rose Bengal score , but the Schirmer test and the tear mucus score did not change . Conclusion : Punctum occlusion therapy in a short-term study improved the rose Bengal score and discomfort score in our patients and thus may be helpful in the treatment of severe dry eye caused by Sjögren syndrome PURPOSE To evaluate the effects of dissolvable collagen punctal plugs on the symptoms , tear stability and volume in aqueous deficient dry eyes . METHODS Sixty-two aqueous deficient dry eye patients of mixed aetiology underwent lacrimal punctal occlusion with dissolvable collagen plugs . The subjects were r and omly allocated to one of two treatment groups : group I ( n = 36 ) had their lower puncta occluded and group II ( n = 26 ) had both their upper and lower puncta occluded . The effectiveness of this treatment was clinical ly assessed by ( 1 ) . scoring subject symptoms and ( 2 ) . measuring the tear parameters of tear thinning time ( TTT ) and tear meniscus height ( TMH ) as indicators of tear stability and volume , respectively . Following baseline measurements , patients were review ed at time intervals of 5 and 12 days post-occlusion . A group of age- and gender-matched normals ( n = 45 ) was recruited for comparison ( group III ) . RESULTS Tear volume and stability were significantly higher in group III compared with I and II at baseline . In the treated groups on both days 5 and 12 : ( 1 ) . symptom score reduced significantly from a median value of 7 to 3 ( p = < 0.001 ) ; ( 2 ) . tear stability increased significantly from a median value of 3 to 5 s by day 5 ( p < or= 0.001 ) ; reduced between days 5 and 12 ( p < 0.05 ) and remained below the stability in group III at all times ; ( c ) . tear volume increased significantly by day 5 in both treatment groups from a median value of 0.13 to 0.20 mm ( p < or=0.001 ) , remained stable by day 12 in group II but reduced in group I ( p < 0.05 ) ; ( d ) . the increase in tear volume was negatively correlated with pre-treatment tear volume ; ( e ) . symptom score correlated with both baseline tear volume and stability . CONCLUSION Collagen plugs improved tear status in the aqueous deficient dry eyes . Occluding both upper and lower puncta with temporary collagen plugs offers no practical beneficial gain compared with occluding just the lower punctum Purpose : To compare the efficacy of topical cyclosporine , punctal occlusion , and a combination for the treatment of dry eye . Methods : Patients with dry eye ( N = 30 ) seen in a university-affiliated private practice were r and omized to 1 of 3 treatments : cyclosporine 0.05 % ophthalmic emulsion ( RESTASIS ) twice daily , lower-lid punctal plugs ( PARASOL ) , or a plugs-cyclosporine combination . Tear volume , ocular surface staining , and artificial tear use were assessed at baseline and 1 , 3 , and 6 months . Results : All treatments improved Schirmer scores by 6 months ( P ≤ 0.005 vs. baseline ) , with plug-containing regimens favored at 1 and 3 months ( P < 0.001 vs. cyclosporine alone ) . Cyclosporine-containing regimens , but not plugs alone , improved rose bengal staining at 3 and 6 months ( P ≤ 0.010 vs. baseline ) . Artificial tear use decreased with plug-containing regimens at 1 month and with all treatments at 3 and 6 months ( P ≤ 0.005 vs. baseline ) . Combination therapy produced the greatest overall improvements and was superior to plugs alone in decreasing artificial tear use at 6 months ( P = 0.012 ) . Conclusions : All 3 regimens effectively treated dry eye . Plug-containing regimens increased wetness initially ; cyclosporine appeared to promote long-term ocular surface health . The effects may be additive . Patients with punctal occlusion may benefit from adjunctive cyclosporine Objectives . The purpose of this report is to describe the impact of punctal occlusion in symptomatic dry eye contact lens wearers and the relation between subjective and objective outcomes . Methods . This study was a r and omized , controlled , double-masked , single center clinical trial . A previously described dry-eye question naire was used to determine subject eligibility . Tear interferometry was performed to evaluate prelens tear film thickness , contact lens center thickness , and postlens tear film thickness . Each subject was r and omly assigned to receive the punctal plugs or a sham procedure . At the outcome examination , the subject completed the dry-eye question naire and answered one question rating the efficacy of the punctal plug treatment in addition to undergoing tear interferometry using an identical protocol as the first visit . Results . Nineteen subjects completed both visits of this study . There was a significant improvement in the dry-eye question naire scores from baseline to the outcome visit for both the plug ( Z = −2.52 , P=0.01 ) and sham groups ( Z = −2.93 , P=0.003 ) . A significant increase in prelens tear film thickness occurred within the sham group from baseline to the outcome visit ( Z = −1.96 , P=0.05 ) , but not for the punctal plug group . No other layers measured by interferometry were shown to change significantly for either group . Conclusions . Results comparing the sham and plug groups were not significantly different from each other with regards to the question naire score and treatment benefit assessment , indicating either the treatment effect was not detected , although present , or punctal occlusion had no treatment effect at all PURPOSE To compare the short-term efficacy of collagen and silicone plugs for treating dry eye using quantitative lacrimal scintigraphy . DESIGN Prospect i ve r and omized clinical trial . METHODS In this institutional study , 24 dry eye patients were evaluated in two groups : group I ( n = 22 eyes ) received collagen plugs and group II ( n = 26 eyes ) received silicone plugs . Comparisons were made with normal control subjects ( n = 22 eyes ) . Data for the Schirmer I test , tear break-up time , and ocular surface staining with rose bengal dye were recorded before and after punctal occlusion . Lacrimal scintigraphy was performed at each time point , and the time to half maximum activity on the ocular surface ( T(1/2 ) ) , and the percentage retention of activity on the ocular surface at the end of the dynamic study ( RI ) were recorded . RESULTS In both patient groups , Schirmer I results , tear break-up times , and rose bengal staining scores improved significantly after plug insertion . Mean T(1/2 ) values and RI values increased significantly in both groups ( P < .0001 for both ) . The differences for these values between groups I and II was statistically insignificant ( P > .05 ) . CONCLUSIONS Collagen and silicone plugs both result ed in significant increases in aqueous tear volume , half-life of nuclear material on the ocular surface , and percentage of nuclear material retention . The groups ' post-insertion values for all parameters were similar . These results suggest that these two plug types have similar efficacy as treatments for dry eye in the short term . Further studies evaluating long-term results are required To compare the effects of treatment with punctal plugs versus artificial tears on visual function for primary Sjögren ’s syndrome with dry eye . Forty-two eyes of 42 patients with primary Sjögren ’s syndrome were enrolled and were allocated r and omly into artificial tears ( AT ) group and punctal plugs ( PP ) group . Ocular Surface Disease Index ( OSDI ) was used , and fluorescent staining for tear film break-up time ( BUT ) , the Schirmer test I ( STI ) and contrast sensitivity was performed before treatment and was repeated 3 months after treatment . A follow-up of 3 months was achieved in 40 eyes of 40 patients , including 19 eyes in artificial tears group and 21 eyes in punctal plugs group . Statistically significant improvements were observed in the OSDI scores ( AT : 52.6 ± 5.7 , 15.9 ± 4.2 ; PP : 55.8 ± 4.9 , 15.1 ± 4.2 ) , corneal fluorescein staining scores ( AT : 2.60 ± 1.76 , 0.30 ± 0.57 ; PP : 1.91 ± 1.60 , 0.09 ± 0.29 ) , STI ( AT : 3.85 ± 2.03 , 8.95 ± 2.72 ; PP : 3.36 ± 1.62 , 11.41 ± 2.65 ) , and BUT ( AT : 2.60 ± 1.39 , 6.00 ± 1.81 ; PP : 2.27 ± 1.12 , 7.82 ± 1.84 ) after treatment compared to those of pre-treatment . The values of STI ( AT : 5.10 ± 1.80 ; PP : 8.05 ± 1.53 ) and BUT ( AT : 3.40 ± 1.31 ; PP : 5.68 ± 1.13 ) in punctal plugs group were significantly more improved than those in the artificial tears group . The medium- and high-level frequencies contrast sensitivities were greatly improved in simulated daylight , night , and glare disability conditions after treatment with artificial tears and punctal plugs . However , the changes in contrast sensitivity did not significantly differ between groups . Both artificial tears and punctal plugs relieved dry eye symptoms , repaired corneal lesions , enhanced tear film stability , and improved contrast sensitivity . Punctal plugs could improve tear film stability and elongate the BUT better than artificial tears PURPOSE To report an increased functional visual acuity , which was recently reported as a simulation of visual function of daily acts of gazing , in dry eye patients after punctal occlusion . DESIGN Prospect i ve comparative interventional study . METHODS We measured ordinary best-corrected visual acuity and functional visual acuity in eight eyes of eight dry eye patients after punctal occlusion , and compared the results with those of 22 eyes of 22 dry eye patients without punctal occlusion . RESULTS Functional visual acuity in dry eye patients after punctal occlusion was 0.962 in decimal notation , which was significantly higher than that of patients without punctal occlusion , 0.283 ( P < .0001 ) . CONCLUSIONS This study shows that punctal occlusion can improve the impaired functional visual acuity of dry eye patients Purpose To evaluate the efficacy of punctal plugs for patients with post-LASIK dry eye . Material s and methods A prospect i ve study was conducted on 25 eyes of 18 patients who underwent LASIK . All eyes fulfilled the Japanese dry-eye criteria and had not responded to conventional treatment with artificial tears by 1 month postsurgery . They were r and omly divided into a plug and a non-plug group . Punctal plugs were inserted into the superior and inferior puncta in the plug group after the 1-month examination . Uncorrected and best corrected visual acuity ( UCVA , BCVA ) , refraction , functional visual acuity ( FVA ) after 10 s eye opening ( FVA 10 ) , surface regularity index ( SRI ) after 10 s eye opening ( SRI 10 ) , corneal sensitivity , Schirmer test , fluorescein staining ( FS ) , tear break-up time ( TBUT ) , and symptoms were compared between the groups 1 and 3 months postsurgery . Changes in these data from 1 to 3 months were also compared between the groups . Results The values in SRI 10 , FS , and TBUT were significantly better in the plug group at 3 months . Changes in the values of UCVA , FVA 10 , FS , TBUT , and symptoms between 1 and 3 months improved significantly in the plug group compared with the non-plug group . Conclusion Our results suggest that punctal occlusion for both puncta is effective for patients with post-LASIK dry eye that can not be controlled by artificial tears alone . Punctal plugs can improve not only the symptoms and tear function , but also the quality of vision , for example FVA Purpose : To compare the efficacies of punctal plug insertion and Botulinum toxin injection in dry eye disease not responding to topical medications . Material s and Methods : A non-controlled r and omized clinical trial of two parallel groups of 60 dry eye patients seen in the clinic not responding to topical medications were divided into two groups . One group received punctal plugs and the other group received Botulinum toxin injections to prevent lacrimal tear drainage . Results : Of a total of 36 patients with a mean age of 44.5 years who received punctal plugs , 50 % of them experienced improvements in the clinical manifestations of their disease . 12/36 ( 33.3 % ) developed plug extrusion , and 6/36 ( 16.7 % ) patients developed conjunctival erosions with irritation that necessitated plug removal within one week of insertion . A total of 24 patients with a mean age of 47.5 years received injections of Botulinum toxin . Of these , 83.3 % had improvement in all of the clinical manifestations of dry eye . 4/24 ( 16.7 % ) had no improvement in the degrees to which they experienced foreign body sensations , 33.3 % reported shampoo entering the eye while showering . All of the patients who received Botulinum toxin injections were satisfied with the results of their treatment , whereas only 72.3 % of the patients who received punctal plugs were satisfied with their results . Conclusion : Botulinum neurotoxin A injections can be a very good alternative to punctal plugs in improving the clinical manifestations of dry eye disease They are associated with the development of fewer and milder complications and with higher levels of patient satisfaction Purpose . To investigate effects of lacrimal drainage occlusion with intracanalicular silicone plugs in hydrogel lens wearers with the symptom of dryness . Effects of rewetting drops in combination with the plugs were also evaluated . Methods . A 6-week , prospect i ve , double masked , placebo-controlled study design was followed . Thirty-five patients ( 26 females and 9 males ) were entered into the study based on specific symptoms and signs of dry eye with hydrogel lens wear . Baseline symptoms , noninvasive prelens tear film break-up time , lens water content , fluorescein , and rose bengal staining were recorded . Herrick Lacrimal Plugs were inserted into both canaliculi of one previously r and omized eye by an independent investigator . The fellow eye was manipulated in a sham procedure . Symptoms and signs were followed over 4 weeks . Nonpreserved rewetting drops were used in both eyes during the 5th week . Symptoms and signs were again followed . Results . Symptoms improved more significantly in the plugged eye than the control eye after insertion of the plugs , and again after use of the drops . This improvement diminished in some of the patients . Prelens tear film break-up time was not significantly changed . Water content of all lenses combined increased only in the plugged eye with the use of drops . Fluorescein staining decreased significantly in the plugged eye . Rose bengal staining showed a slight decrease in the plugged eye . Conclusions . Intracanalicular silicone plugs offer improvement of symptoms and signs of dryness in this population . There seems to be some decrease in improvement of symptoms with the plugs over time . Concurrent use of rewetting drops increases the benefits OBJECTIVE The research ers sought to assess whether the widely used 1994 Cochrane Highly Sensitive Search Strategy ( HSSS ) for r and omized controlled trials ( RCTs ) in MEDLINE could be improved in terms of sensitivity , precision , or parsimony . METHODS A gold st and ard of 1,347 RCT records and a comparison group of 2,400 non-trials were r and omly selected from MEDLINE . Terms occurring in at least 1 % of RCT records were identified . Fifty percent of the RCT and comparison group records were r and omly selected , and the ability of the terms to discriminate RCTs from non-trial records was determined using logistic regression . The best performing combinations of terms were tested on the remaining records and in MEDLINE . RESULTS The best discriminating term was " Clinical Trial " ( Publication Type ) . In years where the Cochrane assessment of MEDLINE records had taken place , the strategies identified few additional unindexed records of trials . In years where Cochrane assessment has yet to take place , " R and omized Controlled Trial " ( Publication Type ) proved highly sensitive and precise . Adding six more search terms identified further , unindexed trials at reasonable levels of precision and with sensitivity almost equal to the Cochrane HSSS . CONCLUSIONS Most reports of RCTs in MEDLINE can now be identified easily using " R and omized Controlled Trial " ( Publication Type ) . More sensitive search es can be achieved by a brief strategy , the Centre for Review s and Dissemination/Cochrane Highly Sensitive Search Strategy ( 2005 revision ) Abstract Aim : To compare collared silicone punctal plugs to intracanalicular SmartPlugs for the treatment of moderate to severe dry eye . Material s and methods : In this prospect i ve , r and omized , single blind , clinical study , 30 patients ( 60 eyes ) who had been diagnosed with moderate to severe dry eye syndrome were enrolled . Study group I ( n = 30 eyes ) received collared silicone punctal plugs and group II ( n = 30 eyes ) received intracanalicular SmartPlugs . Data for the Schirmer I test , tear break-up time , vital staining , subjective symptoms and frequency of artificial tear application were recorded at baseline and 3 months after punctal occlusion . Results : There was no statistical significant difference for these values between group I and II . Conclusions : Although published data show free flow with irrigation and probing after SmartPlug insertion , the clinical effect in the treatment of dry eye appears to be the equally well to collared silicone punctal plugs . It seems likely that difference of design and localization between the treatment groups were of minor importance concerning impeding of natural and supplemental moisture OBJECTIVE To evaluate the efficacy and side effects of oral pilocarpine for the treatment of ocular symptoms in patients with primary Sjögren 's syndrome ( SS ) . METHODS A 12 week , single centre , r and omised controlled study was performed . Twenty nine patients were r and omly assigned to receive oral pilocarpine ( 5 mg twice a day ) , 28 only artificial tears , and 28 inferior puncta occlusion . Patients receiving oral pilocarpine and those with inferior puncta occlusion also received artificial tears . Patients were evaluated at baseline and throughout the study for their subjective global assessment of dry eyes and for their objective assessment of dry eyes ( Schirmer's-I test , rose bengal test , and imprint test ) . RESULTS Patients taking oral pilocarpine had significant improvement in subjective global assessment of dry eyes , as was evaluated by improvement of > 55 mm on a visual analogue scale ( VAS ) for responses to the eye question naire , compared with patients treated with artificial tears ( p<0.001 ) and those with inferior puncta occlusion ( p<0.05 ) . Furthermore , patients receiving oral pilocarpine also showed greater objective improvement , as measured by the rose bengal test ( p<0.05 ) , while Schirmer's-I test showed no differences between the treated groups . Commonly reported adverse events were headache , increased sweating , nausea , and vomiting in the pilocarpine group , while one patient in the inferior puncta occlusion group had blepharitis and was withdrawn from the study . CONCLUSION 10 mg of pilocarpine daily given to patients with SS for 12 weeks had a beneficial effect on subjective eye symptoms , as evaluated by improvement > 55 mm on a VAS . Additionally , an improvement of rose bengal staining was noted , but an increase in tear production , as measured by the Schirmer-I test , was not substantiated PURPOSE To compare retention rates of Super Flex ( Eagle Vision , Memphis , Tennessee , USA ; Softplug-Oasis Medical Inc , Glendora , California , USA ) vs Parasol ( Odyssey Medical , Memphis , Tennessee , USA ; Beaver Visitec International , Waltham , Massachusetts , USA ) punctal plugs . DESIGN R and omized , double-masked , interventional controlled clinical trial . METHODS Institutional study at Hotel Dieu Hospital ( Queen 's University ) of 50 eyes , from patients with moderate to severe dry eye . Each eye from eligible patients was separately r and omized to receive Super Flex or Parasol punctal plugs . The main outcome measure was plug retention at 6 months . Secondary outcome measures included objective tests of Schirmer I ( mm ) , tear meniscus height ( mm ) , tear break-up time ( s ) , inferior fluorescein corneal staining ( National Eye Institute [ NEI ] scale ) , and average lissamine green conjunctival staining ( NEI scale ) . RESULTS Punctal plug retention was significantly different at 6 months ( P = .011 ) . Sixty-eight percent of Parasol plugs were retained compared to 32 % of Super Flex plugs . Parasol plugs required less frequent artificial tear use at 6 months ( P = .024 ) . There was a statistically significant improvement in all secondary outcome measures ( Schirmer , tear meniscus height , tear break-up time , fluorescein corneal staining ) at 6 months within plug groups except conjunctival staining . There were no additional significant differences between groups and no plug complications reported . CONCLUSIONS Punctal plugs improve symptoms of moderate to severe dry eye ; however , retention rates differ significantly . These data will allow us to guide patient decision making for the safe and effective treatment of punctal plugs for moderate to severe dry eye Purpose : To investigate by ultrahigh resolution optical coherence tomography the effect of punctal occlusion on tear menisci in symptomatic and asymptomatic contact lens wearers . Methods : Symptomatic subjects with self-reported dry eyes ( n = 20 ) and asymptomatic subjects ( n = 20 ) were recruited . For each subject , 1 eye was r and omly chosen for both upper and lower punctal occlusion with collagen plugs . Ultrahigh resolution optical coherence tomography imaged both upper and lower tear menisci before punctal occlusion , and 1 , 4 , 7 , and 10 days afterward . Comfort scoring , noninvasive tear break-up time , tear break-up time , and Schirmer test with anesthesia were also performed . Results : Tear meniscus variables in the symptomatic group were lower than those in the asymptomatic group ( P < 0.05 ) at all time points except for day 4 . In the symptomatic group , the tear menisci were increased up to day 4 after punctal occlusion ( P < 0.05 ) . The increase was present only on day 1 in the asymptomatic group . Improvement of comfort scores and noninvasive tear break-up time occurred in both groups after occlusion ( P < 0.05 ) . The comfort scores were linearly correlated with the tear volumes after punctal occlusion , with higher correlation coefficients in the symptomatic group . Conclusions : Punctal occlusion transiently increased tear menisci in symptomatic and asymptomatic lens wearers , with a longer duration in the symptomatic group . For both symptomatic and asymptomatic lens wearers , the increased meniscus volume was associated with improved ocular comfort Purpose To evaluate the effects of temporary canalicular occlusion with silicone plugs on trachomatous dry eye patients who were on maximal tolerable medical therapy . Methods Forty-four trachomatous dry eye patients who had Schirmer testing with topical anaesthetic measuring 5 mm or less and a tear film break-up time of 5 s or less were included . After the lacrimal efficiency test with dissolvable collagen punctal plugs , silicone canalicular plugs were placed in 22 trachomatous dry eye patients . The other 22 patients in the untreated control group were allowed to continue their medical therapy . Pretreatment and post-treatment evaluations included subjective patient assessment , rose Bengal and fluorescein staining , tear film break-up time , Schirmer testing , conjunctival impression cytology and goblet cell counting . Results Six months after plug placement , 18 eyes ( 82 % ) of 22 patients had subjective improvement and all these patients successfully wore plugs for at least 6 months . There were statistically significant differences between the pretreatment and post-treatment test results including rose Bengal and fluorescein staining scores , tear film break-up times and Schirmer testing measurements . Impression cytology showed improvement of squamous metaplasia in 17 eyes ( 77 % ) . Eight of the patients ( 36 % ) were able to decrease dependency on topical therapy . Ten of the patients ( 45 % ) completely stopped using artificial tears . There were statistically significant differences between the two groups in the total symptom scores , staining scores , tear film break-up time , Schirmer testing , impression cytology scores and goblet cell counts . Conclusion In cases where topical tear supplementation is insufficient to relieve the signs and symptoms of severe dry eye and the lacrimal puncta have not already been closed by the trachomatous cicatrising process , occlusion of the canaliculi may be useful to prevent drainage of both natural and artificial tears . Canalicular occlusion improves the objective signs and subjective symptoms and may significantly decrease dependency on tear supplements in selected patients Purpose To evaluate visual function changes after punctal plug ( PP ) occlusion in patients with short breakup time of tear film ( BUT ) type of dry eyes . Methods A prospect i ve comparative study was performed in 43 eyes of 43 dry eye patients with short BUTbreakup time of tear film receiving PP occlusion . Patients were divided into 2 groups as those receiving only upper or only lower occlusion . Functional visual acuity measurements , tear function evaluations , and question naire on satisfaction with treatment in relation to presence of epiphora were performed before and 1 month after PP insertion . Results Twenty eyes of 43 eyes ( 46.5 % ) with only lower occlusion and 17 eyes of 43 eyes ( 39.5 % ) with only upper occlusion showed satisfactory outcomes with treatment . One of 43 eyes ( 2.3 % ) had epiphora . Vital staining scores and BUT values significantly improved in both groups after occlusion . The mean logarithm of the minimum angle of resolution functional visual acuity value significantly improved only in eyes receiving upper PP occlusion . Conclusion Upper PP occlusion seems to be associated not only with improvement of tear stability , vital staining scores , and treatment-related satisfaction but also with better quality of visual function PURPOSE To analyze the efficacy of topical nonpreserved steroids before punctal occlusion in the treatment of severe keratoconjunctivitis sicca associated with Sjögren 's syndrome . METHODS We performed a prospect i ve study including 15 patients , 30 eyes , ( group 1 ) treated with topical nonpreserved steroids for 2 weeks and then punctal occlusion , and 15 patients , 30 eyes , ( group 2 ) treated directly with punctal occlusion . Symptom severity ( 0 - 3 + ) and corneal fluorescein staining ( 0 - 9 + ) were evaluated after a week and after two months , and results were statistically compared between both groups with the t Student test . RESULTS Symptom severity was negative in 67 % of patients of group 1 and in 27 % of patients of group 2 ( p=0.0001 ) after a week , and in 80 % of patients in group 1 and in 33 % of patients of group 2 ( p=0.0003 ) after 2 months . Corneal fluorescein staining was negative in 67 % ( OD ) and 73 % ( OI ) of patients of group 1 and in 33 % ( AO ) of patients of group 2 ( p=0.0001 , AO ) after a week , and in 80 % ( AO ) of patients of group 1 and in 60 % of patients of group 2 ( AO ) ( p=0.0001 , AO ) after 2 months . There were no patients with side effects or complications . CONCLUSIONS Topical nonpreserved steroid therapy for two weeks before punctal occlusion is effective in controlling symptoms and corneal fluorescein staining in patients with severe keratoconjunctivitis sicca associated with Sjögren 's syndrome |
2,249 | 26,985,252 | In contrast , the number of clinical studies is still insufficient to assess their effectiveness , and these studies only demonstrate the absence of serious adverse events . | BACKGROUND Published studies seeking to improve survival in amyotrophic lateral sclerosis ( ALS ) have poor results in humans , although there are several studies in animal models with positive results . | Amyotrophic Lateral Sclerosis ( ALS ) is a rapidly progressive neurodegenerative disorder with fatal prognosis . Cellular therapy has been studied for ALS in various animal models and these advances have highlighted its potential to be a treatment modality . This is a retrospective controlled cohort study of total 57 patients . Out of these , 37 patients underwent autologous bone marrow mononuclear cell transplantation in addition to st and ard rehabilitation and Riluzole . Control group consisted of 20 patients who did not receive cell transplantation . The survival duration since the onset of the disease for both the groups was computed using a Kaplan-Meier Survival analysis and compared using log-rank test . Effect of age at onset , type of onset and lithium on survival duration in the intervention group was analyzed . Mean survival duration of patients in intervention group was 87.76 months which was higher than the control group mean survival duration of 57.38 months . Survival duration was significantly ( p = 0.039 ) higher in people with the onset of the disease below 50 years of age . Limb onset and lithium also showed positive influence on the survival duration . Mean survival duration of the intervention group was also higher than the survival duration of ALS patients in previous epidemiological studies . In addition to the st and ard treatment with Riluzole , early intervention with combination of BMMNCs transplantation and Lithium may have a positive effect on the survival duration in ALS . Prospect i ve r and omized controlled studies with a larger sample size and rigorous methodology are required for conclusive findings Amyotrophic lateral sclerosis ( ALS ) is the most common adult onset motor neuron disease . The etiology and pathogenic mechanisms of the disease remain unknown , and there is no effective treatment . Here we show that intrathecal transplantation of human motor neurons derived from neural stem cells ( NSCs ) in spinal cord of the SOD1G93A mouse ALS model delayed disease onset and extended life span of the animals . When HB1.F3.Olig2 ( F3.Olig2 ) cells , stable immortalized human NSCs encoding the human Olig2 gene , were treated with sonic hedgehog ( Shh ) protein for 5–7 days , the cells expressed motor neuron cell type-specific phenotypes Hb9 , Isl-1 and choline acetyltransferase ( ChAT ) . These F3.Olig2-Shh human motor neurons were transplanted intrathecally in L5–L6 spinal cord of SOD1G93A mice , and at 4 weeks post-transplantation , transplanted F3.Olig2-Shh motor neurons expressing the neuronal phenotype markers NF , MAP2 , Hb9 , and ChAT were found in the ventral horn of the spinal cord . Onset of clinical signs in ALS mice with F3.Olig2-Shh motor neuron implants was delayed for 7 days and life span of animals was significantly extended by 20 days . Our results indicate that this treatment modality of intrathecal transplantation of human motor neurons derived from NSCs might be of value in the treatment of ALS patients without significant adverse effects OBJECTIVE To evaluate the feasibility , safety , and immunological effects of intrathecal and intravenous administration of autologous mesenchymal stem cells ( MSCs ) ( also called mesenchymal stromal cells ) in patients with multiple sclerosis ( MS ) and amyotrophic lateral sclerosis ( ALS ) . DESIGN A phase 1/2 open-safety clinical trial . Patients Fifteen patients with MS ( mean [ SD ] Exp and ed Disability Status Scale [ EDSS ] score , 6.7 [ 1.0 ] ) and 19 with ALS ( mean [ SD ] Amyotrophic Lateral Sclerosis Functional Rating Scale [ ALSFRS ] score , 20.8 [ 8.0 ] ) were enrolled . Intervention After culture , a mean ( SD ) of 63.2 × 10(6 ) ( 2.5 × 10(6 ) ) MSCs was injected intrathecally ( n = 34 ) and intravenously ( n = 14 ) . In 9 cases , MSCs were magnetically labeled with the superparamagnetic iron oxide ferumoxides ( Feridex ) . MAIN OUTCOME MEASURES The main outcome measure was the recording of side effects . Follow-up ( ≤25 months ) included adverse events evaluation , neurological disability assessment by means of the EDSS , magnetic resonance imaging to exclude unexpected pathologies and track the labeled stem cells , and immunological tests to assess the short-term immunomodulatory effects of MSC transplantation . RESULTS Twenty-one patients had injection-related adverse effects consisting of transient fever , and 15 reported headache . No major adverse effects were reported during follow-up . The mean ALSFRS score remained stable during the first 6 months of observation , whereas the mean ( SD ) EDSS score improved from 6.7 ( 1.0 ) to 5.9 ( 1.6 ) . Magnetic resonance imaging visualized the MSCs in the occipital horns of the ventricles , indicating the possible migration of ferumoxides-labeled cells in the meninges , subarachnoid space , and spinal cord . Immunological analysis revealed an increase in the proportion of CD4(+)CD25(+ ) regulatory T cells , a decrease in the proliferative responses of lymphocytes , and the expression of CD40(+ ) , CD83(+ ) , CD86(+ ) , and HLA-DR on myeloid dendritic cells at 24 hours after MSC transplantation . CONCLUSION Transplantation of MSCs in patients with MS and ALS is a clinical ly feasible and relatively safe procedure and induces immediate immunomodulatory effects . Trial Registration clinical trials.gov Identifier : NCT00781872 BACKGROUND The first US Food and Drug Administration approved clinical trial for a stem cell-based treatment of amyotrophic lateral sclerosis has now been completed . OBJECTIVE Primary aims assessed the safety of a direct microinjection-based technique and the toxicity of neural stem cell transplantation to the ventral horn of the cervical and thoracolumbar spinal cord . Results from thoracolumbar-only microinjection groups have been previously published . Cervical and cervical plus thoracolumbar microinjection group perioperative morbidity results are presented . METHODS Eighteen microinjection procedures ( n = 12 thoracolumbar [ T10/11 ] , n = 6 cervical [ C3 - 5 ] ) delivered NSI-566RSC ( Neuralstem , Inc ) , a human neural stem cell , to 15 patients in 5 cohorts . Each injection series comprised 5 injections of 10 μL at 4-mm intervals . The patients in group A ( n = 6 ) were nonambulatory and received unilateral ( n = 3 ) or bilateral ( n = 3 ) thoracolumbar microinjections . The patients in groups B to E were ambulatory and received either unilateral ( group B , n = 3 ) or bilateral ( group C , n = 3 ) thoracolumbar microinjection . Group D and E patients received unilateral cervical ( group D , n = 3 ) or cervical plus bilateral thoracolumbar microinjection ( group E , n = 3 ) . RESULTS Unilateral cervical ( group D , n = 3 ) and cervical plus thoracolumbar ( group E , n = 3 ) microinjections to the ventral horn have been completed in ambulatory patients . One patient developed a postoperative kyphotic deformity prompting completion of a laminoplasty in subsequent patients . Another required reoperation for wound dehiscence and infection . The solitary patient with bulbar amyotrophic lateral sclerosis required perioperative reintubation . CONCLUSION Delivery of a cellular payload to the cervical or thoracolumbar spinal cord was well tolerated by the spinal cord in this vulnerable population . This encouraging finding supports consideration of this delivery approach for neurodegenerative , oncologic , and traumatic spinal cord afflictions Advances in stem cell biology have generated intense interest in the prospect of transplanting stem cells into the nervous system for the treatment of neurodegenerative diseases . Here , we report the results of an ongoing phase I trial of intraspinal injections of fetal-derived neural stems cells in patients with amyotrophic lateral sclerosis ( ALS ) . This is a first-in-human clinical trial with the goal of assessing the safety and tolerability of the surgical procedure , the introduction of stem cells into the spinal cord , and the use of immunosuppressant drugs in this patient population . Twelve patients received either five unilateral or five bilateral ( 10 total ) injections into the lumbar spinal cord at a dose of 100,000 cells per injection . All patients tolerated the treatment without any long-term complications related to either the surgical procedure or the implantation of stem cells . Clinical assessment s ranging from 6 to 18 months after transplantation demonstrated no evidence of acceleration of disease progression due to the intervention . One patient has shown improvement in his clinical status , although these data must be interpreted with caution since this trial was neither design ed nor powered to measure treatment efficacy . These results allow us to report success in achieving the phase I goal of demonstrating safety of this therapeutic approach . Based on these positive results , we can now advance this trial by testing intraspinal injections into the cervical spinal cord , with the goal of protecting motor neuron pools affecting respiratory function , which may prolong life for patients with ALS BACKGROUND AIMS Mesenchymal stem cells/marrow stromal cells ( MSC ) represent a promising tool for stem cell-based clinical trials in amyotrophic lateral sclerosis ( ALS ) . We present the results of long-term monitoring of 19 ALS patients enrolled in two phase I clinical trials of autologous MSC transplantation . METHODS Nineteen patients ( 11 male and eightfemale ) with ALS were enrolled in two consecutive phase I clinical trials . The patients were followed-up for 6 - 9 months and then treated with autologous MSC isolated from bone marrow and implanted into the dorsal spinal cord with a surgical procedure . The patients were monitored regularly before and after transplantation with clinical , psychological and neuroradiologic assessment s every 3 months , at the tertiary referral ALS center in Novara ( Italy ) , until death . RESULTS Follow-up brain magnetic resonance imaging ( MRI ) revealed no structural changes ( including tumor formation ) relative to the baseline throughout the follow-up . There was no deterioration in the psychosocial status and all patients coped well . No clear clinical benefits were detected in these patients but the recruitment and selection of appropriate patients into larger trials will be needed to test the efficacy of the treatment . CONCLUSIONS This study is the first to show the safety of MSC transplantation in the central nervous system during a follow-up of nearly 9 years , and is in support of applying MSC-based cellular clinical trials to neurodegenerative disorders BACKGROUND AIMS Amyotrophic lateral sclerosis ( ALS ) is characterized by the selective death of motor neurons . CD133(+ ) stem cells are known to have the capacity to differentiate into neural lineages . Stem cells may provide an alternative treatment for ALS and other neurodegenerative diseases . METHODS Five men and five women ( aged 38 - 62 years ) with confirmed ALS were included in this study . Our institutional ethics and research committees approved the protocol . After informed consent was obtained , patients underwent Hidrogen-Magnetic Resonance Imaging ( H-MRI ) spectroscopy and were given scores according to an ALS functional rating scale , Medical Research Council power muscle scale and daily living activities . Bone marrow was stimulated with 300 microg filgrastim subcutaneously daily for 3 days . Peripheral blood mononuclear cells were obtained after admission by leukapheresis . The cell suspension was conjugated with anti-human CD133 superparamagnetic microbeads , and linked cells were isolated in a magnetic field . The isolated cells ( 2.5 - 7.5x10(5 ) ) were resuspended in 300 microL of the patient 's cerebrospinal fluid , and implanted in motor cortexes using a Hamilton syringe . Ten patients with confirmed ALS without transplantation were used as a control group . Patients were followed up for a period of 1 year . RESULTS The autologous transplantation of CD133(+ ) stem cells into the frontal motor cortex is a safe and well-tolerated procedure in ALS patients . The survival of treated patients was statistically higher ( P=0.01 ) than untreated control patients . CONCLUSIONS Stem-cell transplantation in the motor cortex delays ALS progression and improves quality of life BACKGROUND Amyotrophic lateral sclerosis ( ALS ) is a fatal neurodegenerative disorder characterized by progressive loss of spinal cord and cortical motoneurons . Despite improved underst and ing of the mechanisms underlying ALS , in clinical practice the management of ALS remains essentially supportive and focused on symptom relief . However , over the past few years stem cell research has exp and ed greatly as a tool for developing potential new therapies for treating incurable neurodegenerative diseases . METHODS Thirteen patients with sporadic amyotrophic lateral sclerosis ( SALS ) were included in this study , and bone marrow (BM)-derived hematopoietic progenitor stem cells were used . We selected patients with bulbar involvement and severe loss of movement . Our aim was to put the stem cells into the end of the brain stem and at the beginning of the spinal cord because the blood-brain barrier is intact in ALS and this region was the most affected part in our patients . Under general anesthesia , a total laminectomy was performed at the C1-C2 level . Stem cells were injected to the anterior part of the spinal cord . RESULTS During the follow-up of 1 year after stem cell implantation , nine patients became much better compared with their pre-operative status , confirmed by electro neuro myography ( ENMG ) . One patient was stable without any decline or improvement in his status . Three patients died 1.5 , 2 and 9 months , respectively , after stem cell therapy as a result of lung infection and myocardial infa rct ion ( MI ) . DISCUSSION These results show that stem cell therapy is a safe , effective and promising treatment for ALS patients The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells ( BMNCs ) and , ultimately , to look for histopathological signs of cellular neurotrophism in amyotrophic lateral sclerosis ( ALS ) patients . We conducted an open single arm phase I trial . After 6 months observation , autologous BMNCs were infused into the posterior spinal cord funiculus . Safety was the primary endpoint and was defined as the absence of serious transplant-related adverse events . In addition , forced vital capacity ( FVC ) , ALS-functional rating scale ( ALS-FRS ) , Medical Research Council scale for assessment of muscle power ( MRC ) , and Norris scales were assessed 6 and 3 months prior to the transplant and quarterly afterward for 1 year . Pathological studies were performed in case of death . Eleven patients were included . We did not observe any severe transplant-related adverse event , but there were 43 nonsevere events . Twenty-two ( 51 % ) resolved in ≤2 weeks and only four were still present at the end of follow-up . All were common terminology criteria for adverse events grade ≤2 . No acceleration in the rate of decline of FVC , ALS-FRS , Norris , or MRC scales was observed . Four patients died on days 359 , 378 , 808 , and 1,058 post-transplant for reasons unrelated to the procedure . Spinal cord pathological analysis showed a greater number of motoneurons in the treated segments compared with the untreated segments ( 4.2 ± 0.8 motoneurons per section [ mns per sect ] and 0.9 ± 0.3 mns per sect , respectively ) . In the treated segments , motoneurons were surrounded by CD90 + cells and did not show degenerative ubiquitin deposits . This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence strongly suggesting their neurotrophic activity BACKGROUND AND AIMS The aim of this study was to evaluate and characterize the feasibility and safety of bone marrow-derived cell ( BMC ) mobilization following repeated courses of granulocyte-colony stimulating factor ( G-CSF ) in patients with amyotrophic lateral sclerosis ( ALS ) . METHODS Between January 2006 and March 2007 , 26 ALS patients entered a multicenter trial that included four courses of BMC mobilization at 3-month intervals . In each course , G-CSF ( 5 microg/kg b.i.d . ) was administered for four consecutive days ; 18 % mannitol was also given . Mobilization was monitored by flow cytometry analysis of circulating CD34(+ ) cells and by in vitro colony assay for clonogenic progenitors . Co-expression by CD34(+ ) cells of CD133 , CD90 , CD184 , CD117 and CD31 was also assessed . RESULTS Twenty patients completed the four-course schedule . One patient died and one refused to continue the program before starting the mobilization courses ; four discontinued the study protocol because of disease progression . Overall , 89 G-CSF courses were delivered . There were two severe adverse events : one prolactinoma and one deep vein thrombosis . There were no discontinuations as a result of toxic complications . Circulating CD34(+ ) cells were monitored during 85 G-CSF courses and were always markedly increased ; the range of median peak values was 41 - 57/microL , with no significant differences among the four G-CSF courses . Circulating clonogenic progenitor levels paralleled CD34(+ ) cell levels . Most mobilized CD34(+ ) cells co-expressed stem cell markers , with a significant increase in CD133 co-expression . CONCLUSIONS It is feasible to deliver repeated courses of G-CSF to mobilize a substantial number of CD34(+ ) cells in patients with ALS ; mobilized BMC include immature cells with potential clinical usefulness Our objective was to assess the incidence of amyotrophic lateral sclerosis ( ALS ) , and its temporal variations , between 1997 and 2007 . The study was based on data prospect ively gathered by the referral ALS ‘ expert centre ’ of the Regional University Hospital of Limousin ( 710,792 inhabitants ) . Patients were included if they were diagnosed with ALS according to the revised El Escorial criteria either at the time of diagnosis or at subsequent follow-up , and if they resided in Limousin when diagnosed . We identified a high crude incidence ( 2.5/100,000 ) . When age-st and ardized for the 1999 French population , the mean annual incidence was 2.0/100,000 inhabitants ( 95 % CI 1.8–2.3 ) overall and 4.4 ( 95 % CI 3.6–5.2 ) in the 45–74 years age group . Crude incidence by age groups showed a progressive increase up to 85 years , followed by a sharp decrease thereafter . Age at diagnosis was particularly high in our population ( median , 69.4 years ) . Incidence of ALS in Limousin was consistent with previous work published by European population -based registries . The atypical epidemiology was explained in part by Limousin 's older aged population . It is proposed that our referral centre will become a population -based registry BACKGROUND No United States-based clinical trials have attempted delivery of biological therapies directly to the spinal cord for treatment of amyotrophic lateral sclerosis ( ALS ) because of the lack of a meaningful US Food and Drug Administration-authorized cell c and i date and a vali date d delivery approach . OBJECTIVE To assess safety of delivery of a neural stem cell-based treatment into the upper lumbar segments of the ALS spinal cord in the first US Food and Drug Administration-authorized phase I trial . METHODS Each microinjection series comprised 5 injections ( 10 μL/injection ) separated by 4 mm . Each injection deposited 100,000 neural stem cells derived from a fetal spinal cord . Twelve patients were treated with either unilateral or bilateral injections . Group A , nonambulatory patients , underwent unilateral ( n = 3 ) or bilateral ( n = 3 ) lumbar microinjections . Groups B and C were ambulatory ( n = 3 each ) and , respectively , received unilateral or bilateral injections . Patients are followed clinical ly and radiologically to assess potential toxicity of the procedure . RESULTS Twelve patients have received a transplant . There was one instance of transient intraoperative somatosensory-evoked potentials depression . In the immediate postoperative period , there was 1 episode of urinary retention requiring Foley catheter reinsertion . By discharge , none had a documented motor function decrement . Two patients required readmission and reoperation for cerebrospinal fluid leak or suprafascial wound dehiscence ( n = 1 each ) . Two deaths occurred at 8 and 13 months postsurgery ; neither was related to the surgical transplant . CONCLUSION Our experience in 12 patients supports the procedural safety of unilateral and bilateral intraspinal lumbar microinjection . Completion of this phase I safety trial is planned by proceeding to cervical and combined cervical + lumbar microinjections in ALS patients The US Food and Drug Administration – approved trial , “ A Phase 1 , Open‐Label , First‐in‐Human , Feasibility and Safety Study of Human Spinal Cord‐Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis , Protocol Number : NS2008‐1 , ” is complete . Our overall objective was to assess the safety and feasibility of stem cell transplantation into lumbar and /or cervical spinal cord regions in amyotrophic lateral sclerosis ( ALS ) subjects |
2,250 | 23,038,617 | Nonetheless the clinical question remains : is immediate routine lumbar spine imaging more effective than usual care without imaging in patients with low back pain and no suggestion of “ red flags . ” | STUDY SUMMARY Lumbar spinal imaging is commonly utilized in the evaluation of low back pain .
The rationale for imaging , either plain radiographs , computed tomography ( CT ) , or magnetic resonance imaging ( MRI ) , is primarily based on identifying anatomical sources of pain .
Unfortunately , the correlation between findings on imaging and clinical symptoms can be limited . | BACKGROUND Management of degenerative spondylolisthesis with spinal stenosis is controversial . Surgery is widely used , but its effectiveness in comparison with that of nonsurgical treatment has not been demonstrated in controlled trials . METHODS Surgical c and i date s from 13 centers in 11 U.S. states who had at least 12 weeks of symptoms and image-confirmed degenerative spondylolisthesis were offered enrollment in a r and omized cohort or an observational cohort . Treatment was st and ard decompressive laminectomy ( with or without fusion ) or usual nonsurgical care . The primary outcome measures were the Medical Outcomes Study 36-Item Short-Form General Health Survey ( SF-36 ) bodily pain and physical function scores ( 100-point scales , with higher scores indicating less severe symptoms ) and the modified Oswestry Disability Index ( 100-point scale , with lower scores indicating less severe symptoms ) at 6 weeks , 3 months , 6 months , 1 year , and 2 years . RESULTS We enrolled 304 patients in the r and omized cohort and 303 in the observational cohort . The baseline characteristics of the two cohorts were similar . The one-year crossover rates were high in the r and omized cohort ( approximately 40 % in each direction ) but moderate in the observational cohort ( 17 % crossover to surgery and 3 % crossover to nonsurgical care ) . The intention-to-treat analysis for the r and omized cohort showed no statistically significant effects for the primary outcomes . The as-treated analysis for both cohorts combined showed a significant advantage for surgery at 3 months that increased at 1 year and diminished only slightly at 2 years . The treatment effects at 2 years were 18.1 for bodily pain ( 95 % confidence interval [ CI ] , 14.5 to 21.7 ) , 18.3 for physical function ( 95 % CI , 14.6 to 21.9 ) , and -16.7 for the Oswestry Disability Index ( 95 % CI , -19.5 to -13.9 ) . There was little evidence of harm from either treatment . CONCLUSIONS In nonr and omized as-treated comparisons with careful control for potentially confounding baseline factors , patients with degenerative spondylolisthesis and spinal stenosis treated surgically showed substantially greater improvement in pain and function during a period of 2 years than patients treated nonsurgically . ( Clinical Trials.gov number , NCT00000409 [ Clinical Trials.gov ] . ) BACKGROUND CONTEXT There is mounting evidence supporting the efficacy of bone morphogenetic protein ( BMP ) for both anterior interbody and posterolateral lumbar fusion . However , the relative cost of BMP remains an important concern for physicians , hospitals , and payers . PURPOSE The purpose of this study is to report on the perioperative costs for patients treated with rhBMP-2 as compared with an iliac crest bone graft ( ICBG ) supplemented with graft extenders . STUDY DESIGN / SETTING A prospect i ve r and omized controlled trial of rhBMP-2/ACS ( Infuse Bone Graft ; Medtronic Sofamor Danek , Memphis , TN ) versus ICBG+/-graft extender for lumbar spine fusion in patients over 60 years old . PATIENT SAMPLE One hundred two patients over 60 years old who required a posterolateral lumbar spine fusion r and omized between receiving rhBMP-2/ACS or ICBG . OUTCOME MEASURES All health-care costs over the first 3 months after surgery . METHODS As part of a prospect i ve r and omized trial of rhBMP-2/ACS versus ICBG+/-graft extender for lumbar spine fusion , all costs over the first 3 months after surgery were directly recorded by a dedicated coder funded by Norton Healthcare , Louisville , KY . A dedicated research nurse also followed all patients throughout their hospital stay and posthospitalization recovery to identify any adverse events or additional outpatient medical care . RESULTS Fifty patients received rhBMP-2/ACS and 52 underwent ICBG harvest . The mean hospital cost for the index admission was $ 24,736 for the rhBMP-2/ACS group and $ 21,138 for the ICBG group . Mean inpatient physician costs were $ 5,082 in the rhBMP-2/ACS group and $ 5,316 in the ICBG group . Costs associated with posthospital rehabilitation averaged $ 4,906 in the rhBMP-2/ACS group versus $ 6,820 in the ICBG group . Total payer expenditure for the 3-month perioperative period averaged $ 33,860 in the rhBMP-2/ACS group and $ 37,227 in the ICBG group . CONCLUSIONS The hospital carries the cost burden associated with the utilization of rhBMP-2/ACS . In contrast , the payer in a Diagnosis-Related Group ( DRG ) model achieves a net savings , based primarily on the decreased payment for inpatient rehabilitation , but also on decreased hospital reimbursement , physician costs , and other outpatient services PURPOSE We sought to determine whether percutaneous vertebroplasty -- which involves the injection of cement to stabilize a fractured vertebral body -- may be an effective treatment for vertebral fracture . METHODS We enrolled 79 consecutive osteoporotic patients ( 24 men and 55 women ; ages 51 to 93 years ) presenting with acute vertebral fractures . Clinical characteristics and bone densitometry were measured at baseline . Pain scores ( on a 0 to 25 scale ) and levels of function ( on a 0 to 20 scale ) were recorded on presentation , at 24 hours , at 6 weeks , and 6 to 12 months after therapy . RESULTS Fifty-five patients ( 70 % ) were treated by percutaneous vertebroplasty and 24 ( 30 % ) were treated by conservative therapy alone . They were followed for a mean of 215 days ( range , 57 to 399 days ) . The baseline clinical characteristics , bone densitometry , and fracture data were similar in the two groups . Twenty-four hours after vertebroplasty , there was a 53 % reduction in pain scores ( from 19 to 9 ; P = 0.0001 ) and a 29 % improvement in physical functioning ( from 14 to 18 ; P = 0.0001 ) , whereas pain scores and physical functioning remained unchanged at 24 hours in the patients treated conservatively ( both P = 0.0001 compared with the changes after percutaneous vertebroplasty ) . Thirteen patients ( 24 % ) treated by percutaneous vertebroplasty were able to cease all analgesia after 24 hours ( P = 0.0001 compared with none of the 24 patients treated conservatively ) . Clinical outcomes at 6 weeks and 6 to 12 months were similar in both groups . CONCLUSION When compared with conservative therapy , percutaneous vertebroplasty results in prompt pain relief and rapid rehabilitation . In experienced h and s , it is a safe and effective procedure for treating acute osteoporotic vertebral compression fractures BACKGROUND The management of degenerative spondylolisthesis associated with spinal stenosis remains controversial . Surgery is widely used and has recently been shown to be more effective than nonoperative treatment when the results were followed over two years . Questions remain regarding the long-term effects of surgical treatment compared with those of nonoperative treatment . METHODS Surgical c and i date s from thirteen centers with symptoms of at least twelve weeks ' duration as well as confirmatory imaging showing degenerative spondylolisthesis with spinal stenosis were offered enrollment in a r and omized cohort or observational cohort . Treatment consisted of st and ard decompressive laminectomy ( with or without fusion ) or usual nonoperative care . Primary outcome measures were the Short Form-36 ( SF-36 ) bodily pain and physical function scores and the modified Oswestry Disability Index at six weeks , three months , six months , and yearly up to four years . RESULTS In the r and omized cohort ( 304 patients enrolled ) , 66 % of those r and omized to receive surgery received it by four years whereas 54 % of those r and omized to receive nonoperative care received surgery by four years . In the observational cohort ( 303 patients enrolled ) , 97 % of those who chose surgery received it whereas 33 % of those who chose nonoperative care eventually received surgery . The intent-to-treat analysis of the r and omized cohort , which was limited by nonadherence to the assigned treatment , showed no significant differences in treatment outcomes between the operative and nonoperative groups at three or four years . An as-treated analysis combining the r and omized and observational cohorts that adjusted for potential confounders demonstrated that the clinical ly relevant advantages of surgery that had been previously reported through two years were maintained at four years , with treatment effects of 15.3 ( 95 % confidence interval , 11 to 19.7 ) for bodily pain , 18.9 ( 95 % confidence interval , 14.8 to 23 ) for physical function , and -14.3 ( 95 % confidence interval , -17.5 to -11.1 ) for the Oswestry Disability Index . Early advantages ( at two years ) of surgical treatment in terms of the secondary measures of bothersomeness of back and leg symptoms , overall satisfaction with current symptoms , and self-rated progress were also maintained at four years . CONCLUSIONS Compared with patients who are treated nonoperatively , patients in whom degenerative spondylolisthesis and associated spinal stenosis are treated surgically maintain substantially greater pain relief and improvement in function for four years OBJECTIVE To assess the safety and efficacy of percutaneous vertebroplasty for the treatment of acute osteoporotic vertebral fractures . DESIGN A prospect i ve , non-r and omised , " intention-to-treat " 2-year study . PATIENTS AND SETTING 126 consecutive patients ( 39 men and 87 women , aged 51 - 95 years ) with acute osteoporotic vertebral fractures presenting to St George Hospital from November 2000 to December 2002 . They comprised 88 patients treated by percutaneous vertebroplasty and 38 by conservative therapy . MAIN OUTCOME MEASURES Primary outcomes --changes in patients ' pain score and level of function recorded at 24 hours , 6 weeks , 6 - 12 months and 24 months after therapy . Secondary outcomes --occurrence of new clinical or radiological vertebral fractures and survival at 2 years . RESULTS Three minor complications ( fractured pedicle and psoas muscle haemorrhage ) occurred in the vertebroplasty group during the first year of the study . Outcomes in vertebroplasty-treated patients ( 60 % reduction in visual analogue pain scores from 20 to 8 ; P < 0.001 ) , a rapid return to normal function ( 29 % improvement in physical functioning from 14 to 18 ; P < 0.001 ) and lower rates of hospitalisation ( 43 % reduction in the mean number of hospital bed-days occupied ) were better than those treated conservatively ( P < 0.001 for the comparison of all variables at 24 hours ) . Lower pain scores persisted in the vertebroplasty-treated group at 6 weeks ( P < 0.001 ) , but no differences between the two groups were evident at 12 and 24 months . In the vertebroplasty-treated group compared with the control group , the rates of new vertebral fractures ( clinical ly and by radiographic assessment ) ( hazard ratio , 1.13 ; 95 % CI , 0.52 - 2.46 ; P = 0.76 ) and death ( hazard ratio , 1.07 ; 95 % CI , 0.42 - 2.76 ; P = 0.89 ) showed no significant difference . CONCLUSION The analgesic benefit of percutaneous vertebroplasty and the low complication rates suggest that it is a useful therapy for acute painful osteoporotic vertebral fractures PURPOSE To prospect ively assess the short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures ( VCF ) treated with percutaneous vertebroplasty ( PV ) compared with optimal pain medication ( OPM ) . METHODS R and omization of patients in 2 groups : treatment by PV or OPM . After 2 weeks , patients from the OPM arm could change therapy to PV . Patients were evaluated 1 day and 2 weeks after treatment . Visual analog score ( VAS ) for pain and analgesic use were assessed before , and 1 day and 2 weeks after start of treatment . Quality of Life Question naire of the European Foundation for Osteoporosis ( QUALEFFO ) and Rol and -Morris Disability ( RMD ) question naire scores were assessed before and 2 weeks after start of treatment . Follow-up scores in patients requesting PV treatment after 2 weeks OPM treatment were compared with scores during their OPM period . RESULTS Eighteen patients treated with PV compared with 16 patients treated with OPM had significantly better VAS and used less analgesics 1 day after treatment . Two weeks after treatment , the mean VAS was less but not significantly different in patients treated with OPM , whereas these patients used significantly less analgesics and had better QUALEFFO and RMD scores . Scores in the PV arm were influenced by occurrence of new VCF in 2 patients . After 2 weeks OPM , 14 patients requested PV treatment . All scores , 1 day and 2 weeks after PV , were significantly better compared with scores during conservative treatment . CONCLUSION Pain relief and improvement of mobility , function , and stature after PV is immediate and significantly better in the short term compared with OPM 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 . R and omized clinical trial . Objective . To perform a cost-utility analysis using actual cost data from a r and omized clinical trial of patients over 60 years old who underwent posterolateral fusion using either rhBMP-2/ACS or iliac crest bone graft ( ICBG ) . Summary Background Data . Bone morphogenetic protein has been shown to be an effective bone graft substitute for spine fusion . However , a clinical trial-based economic analysis of rhBMP-2/ACS compared with iliac crest bone graft has not been done . Methods . Patients over 60 years old requiring decompression and posterolateral fusion were r and omized to rhBMP-2/ACS ( n = 50 ) or ICBG ( n = 52 ) . A dedicated hospital coder and research nurse tracked each patient to determine direct costs of inpatient care and all postoperative healthcare encounters up to 2 years after surgery . Preoperative and 2-year-postoperative SF-6D utility scores for each patient were determined . A decision tree was created , which included the probability of complications , need for additional treatments and revision surgery ; and the costs associated with initial surgery and treatment for complications and additional treatment for continued spine symptoms ; and utility scores . Results . The mean total 2-year cost for care ( excluding complication and additional spine treatment costs ) was $ 34,235 in the ICBG group and $ 36,530 in the rhBMP-2/ACS group . For the entire group , the mean cost to treat a major complication was $ 10,888 , the cost of revision surgery for nonunion was $ 46,852 , and additional treatment for spine-related events was $ 5892 . In the ICBG group , 8 patients had complications ; 20 had additional interventions , 5 of whom required revision for nonunion . In the rhBMP-2/ACS group , 6 patients had complications , 10 had additional interventions , and 1 required revision for nonunion . The cost of using rhBMP-2/ACS was $ 39,967 with a 0.11 mean improvement in SF-6D ; and for ICBG the cost was $ 42,286 with a mean improvement of 0.10 in SF-6D . Conclusion . There are more complications , increased need for additional treatment and revision surgery in patients over 60 years old receiving ICBG compared with rhBMP-2/ACS . This may account for higher costs and lower improvements in utility seen in patients receiving ICBG compared with rhBMP-2/ACS in this study population BACKGROUND Lumbar spine radiography has limited use in diagnosing the cause of acute low back pain . Consensus-based guidelines recommend that lumbar spine x-rays are not used routinely . However there have been no studies of the effect of referral for radiography at first presentation with low back pain in primary care . AIM To compare short and long-term physical , social , and psychiatric outcomes for patients with low back pain who are referred or not referred for lumbar spine x-ray at first presentation in general practice . DESIGN OF STUDY A r and omised unblinded controlled trial with an observational arm to enable comparisons to be made with patients not recruited to the trial . SETTING Ninety-four general practice s in south London and the South Thames region . METHOD Patients consulting their general practitioner ( GP ) with low back pain at first presentation were recruited to a r and omised controlled trial ( RCT ) or to an observational group . Patients in the trial were r and omly allocated to immediate referral for x-ray or to no referral . All patients were asked to complete question naires initially , and then at six weeks and one year after recruitment . RESULTS Six hundred and fifty-nine patients were recruited over 26 months : 153 to the r and omised trial and 506 to the observational arm . In the RCT referral for x-ray had no effect on physical functioning , pain or disability , but was associated with a small improvement in psychological wellbeing at six weeks and one year . These findings were supported by the observational study in which there were no differences between the groups in physical outcomes after adjusting for length of episode at presentation ; however , those referred for x-ray had lower depression scores . CONCLUSIONS Referral for lumbar spine radiography for first presentation of low back pain in primary care is not associated with improved physical functioning , pain or disability . The possibility of minor psychological improvement should be balanced against the high radiation dose involved STUDY DESIGN A prospect i ve cohort study of patients with lumbar spinal stenosis recruited from the practice s of orthopedic surgeons and neurosurgeons throughout Maine . OBJECTIVE To assess 4-year outcomes for patients with lumbar spinal stenosis treated surgically or nonsurgically . SUMMARY OF BACKGROUND DATA Surgery for lumbar spinal stenosis has increased dramatically despite the lack of r and omized trials comparing surgical with nonsurgical treatments . Long-term evaluation of surgical series has documented deterioration in initial symptomatic improvement , but few studies have compared long-term outcomes of surgical and nonsurgical treatment . METHODS Eligible , consenting patients had baseline interviews with mailed follow-up question naires at 3 , 6 , and 12 months , then annually thereafter . Clinical data were obtained at baseline from a physician question naire . Outcomes included patient-reported symptoms of leg and back pain , functional status , and satisfaction . RESULTS Of 148 patients with lumbar spinal stenosis initially enrolled , 4-year outcomes were available on 119 patients ( 80.4 % ) : 67 of 81 ( 83 % ) treated surgically and 52 of 67 ( 78 % ) treated nonsurgically . The surgically treated patients had more severe symptoms and worse functional status at baseline and better outcomes at 4-year evaluation than the nonsurgically treated patients . After 4 years , 70 % of the surgically treated and 52 % of the nonsurgically treated patients reported that their predominant symptom , either leg or back pain , was better ( P = 0.05 ) . Satisfaction of patients with their current state at 4 years was reported by 63 % of the surgically treated and 42 % of the nonsurgically treated patients ( P = 0.04 ) . Surgical treatment remained a significant determinant of 4-year satisfaction , even after adjustment for other independent predictors ( P = 0.001 ) . For the nonsurgically treated patients , there was no significant change in outcomes over 4 years , whereas the initial improvement seen in the surgically treated patients modestly decreased over the subsequent 4 years . CONCLUSIONS For the patients with severe lumbar spinal stenosis , surgical treatment was associated with greater improvement in patient-reported outcomes than nonsurgical treatment at 4-year evaluation , even after adjustment for differences in baseline characteristics among treatment groups . The relative benefit of surgery declined over time but remained superior to nonsurgical treatment . Outcomes for the nonsurgically treated patients improved modestly and remained stable over 4 years . Determining whether outcomes continue to converge will require longer-term evaluation Study Design . Economic evaluation provides a framework to explicitly measure and compare the value of alternative medical interventions in terms of their clinical , health-related quality -of-life , and economic outcomes . Comput-erized economic models can help inform the design of future prospect i ve studies by identifying the cost-drivers , the most uncertain parameter estimates , and the parameters with the greatest impact on the results and inferences . Objective . An economic analysis of bone morphogenetic protein versus autogenous iliac crest bone graft for single-level anterior lumbar fusion poses several method ologic challenges . This article describes how such an economic evaluation may be framed and design ed , while enumerating challenges , offering some solutions , and suggesting an agenda for future research . Summary of Background Data . An evidence -based modeling approach can incorporate epidemiologic , clinical , and economic data from several sources including r and omized clinical trials , peer- review ed literature , and expert opinion . Sensitivity analyses can be conducted by varying key parameter estimates within a reasonable range to assess the impact on the results and inferences . Results . Preliminary results suggest that from a payer perspective , the upfront price of bone morphogenetic protein is likely to be entirely offset by reductions in the use of other medical re sources . That is , bone morphogenetic protein appears to be cost neutral . The cost offsets were attributable largely to prevention of pain and complications associated with autogenous iliac crest bone graft , as well as reduction of the costs associated with fusion failures . Conclusions . Future research should focus on quantifying the health-related quality -of-life impact of bone morphogenetic protein relative to autogenous iliac crest bone graft , as well as the impact on lost productivity Study Design . Clinical r and omized study . Objective . The aim of this study is to compare percutaneous vertebroplasty ( PVP ) to conservative treatment of patients with osteoporotic vertebral fractures in a clinical r and omized study with respect to pain , physical and mental outcome , and to asses the risk of adjacent fractures . Summary of Background Data . PVP is a therapeutic procedure performed to reduce pain in vertebral lesions . Despite the lack of comparative r and omized clinical trials PVP is generally seen as a safe and efficient procedure for painful osteoporotic fractures . Methods . Fifty patients ( 41 females ) were included from January 2001 until January 2008 . Patients with acute ( < 2 weeks ) and subacute ( between 2 and 8 weeks ) osteoporotic fractures were included and r and omized to either PVP or conservative treatment . Pain was assessed with a visual analogue scale and physical and mental outcome were assessed by vali date d question naires and tests . Tests , question naires , and plain radiographs were performed at the inclusion and after 3 months . Results . Reduction in pain from initial visit to 3-month follow-up was comparable in the 2 groups ( P = 0.33 ) from approximate visual analogue scale 8.0 to visual analogue scale 2.0 , intragroup difference was significant ( P = 0.00 ) . Reduction in pain in the PVP group was immediate 12 to 24 hours after the procedure ( P = 0.00 ) . There was no significant difference in the other parameters when comparing the results at inclusion and after 3 months within both groups and between the groups after 3 months with a few exceptions . We observed 2 adjacent fractures in the PVP group and non in the conservative group . Conclusion . The majority of patients with acute or subacute painful osteoporotic compression fractures in the spine will recover after a few months of conservative treatment . The risk of adjacent fractures needs further research . No major adverse events were observed |
2,251 | 25,517,475 | There was also no significant difference in survival or neurologic outcome at hospital discharge between active compression-decompression resuscitation or impedance threshold device and st and ard cardiopulmonary resuscitation .
The meta-regression indicated that this minimal effect might be modified by two important prognostic factors , that is , witnessed status and response time .
After adjustment of these two factors , impedance threshold device appeared to improve return of spontaneous circulation , which could be further augmented by advanced airway use .
Active compression-decompression resuscitation or impedance threshold device seemed not to improve return of spontaneous circulation in out-of-hospital cardiac arrest patients .
The meta-regression indicated two probable prognostic factors causing this minimal effect . | OBJECTIVE Active compression-decompression resuscitation and impedance threshold device are proposed to improve survival of patients of cardiac arrest by lowering intrathoracic pressure and increasing cardiac output .
The results of clinical studies of active compression-decompression resuscitation or impedance threshold device were controversial .
This meta analysis pooled results of r and omized controlled trials to examine whether active compression-decompression resuscitation or impedance threshold device would improve outcomes of out-of-hospital cardiac arrest in comparison with st and ard cardiopulmonary resuscitation and to explore factors modifying these effects . | Background Prehospital resuscitation for patients with major trauma emphasizes a load- and -go principle . For traumatic cardiac arrest ( TCA ) patients , the administration of vasopressors remains under debate . This study evaluated the effectiveness of epinephrine in the prehospital setting for patients with TCA . Methods We conducted a retrospective cohort study using a prospect ively collected registry for out-of-hospital cardiac arrest in Taipei . Enrollees were ≥18 years of age with TCA . Patients with signs of obvious death like decapitation or rigor mortis were excluded . Patients were grouped according to prehospital administration , or lack thereof , of epinephrine . Outcomes were sustained ( ≥2 h ) recovery of spontaneous circulation ( ROSC ) and survival to discharge . A subgroup analysis was performed by stratified total prehospital time . Results From June 1 2010 to May 31 2013 , 514 cases were enrolled . Epinephrine was administered in 43 ( 8.4 % ) cases . Among all patients , sustained ROSC and survival to discharge was 101 ( 19.6 % ) and 20 ( 3.9 % ) , respectively . The epinephrine group versus the non-epinephrine group had higher sustained ROSC ( 41.9 % vs. 17.6 % , p < 0.01 ) and survival to discharge ( 14.0 % vs. 3.0 % , p < 0.01 ) . The adjusted odds ratios ( ORs ) of epinephrine effect were 2.24 ( 95 % confidence interval ( CI ) 1.05 - 4.81 ) on sustained ROSC , and 2.94 ( 95 % CI 0.85 - 10.15 ) on survival to discharge . Subgroup analysis showed increased ORs of epinephrine effect on sustained ROSC with a longer prehospital time . Conclusion Among adult patients with TCA in an Asian metropolitan area , administration of epinephrine in the prehospital setting was associated with increased short-term survival , especially for those with a longer prehospital time Objective : To assess whether intermittent impedance of inspiratory gas exchange improves hemodynamic parameters , 48-hr survival , and neurologic outcome in a swine model of asphyxial cardiac arrest treated with active compression-decompression cardiopulmonary resuscitation . Design : Prospect i ve , r and omized , double-blind study . Setting : Laboratory investigation . Subjects : Thirty healthy L and race/Large-White piglets of both sexes , aged 10 to 15 wks , whose average weight was 19 ± 2 kg . Interventions : At approximately 7 mins following endotracheal tube clamping , ventricular fibrillation was induced and remained untreated for another 8 mins . Before initiation of cardiopulmonary resuscitation , animals were r and omly assigned to either receive active compression-decompression cardiopulmonary resuscitation plus a sham impedance threshold device ( control group , n = 15 ) , or active compression-decompression cardiopulmonary resuscitation plus an active impedance threshold device ( experimental group , n = 15 ) . Electrical defibrillation was attempted every 2 mins until return of spontaneous circulation or asystole . Measurements and Main Results : Return of spontaneous circulation was observed in six ( 40 % ) animals treated with the sham valve and 14 ( 93.3 % ) animals treated with the active valve ( p = .005 , odds ratio 21.0 , 95 % confidence interval 2.16–204.6 ) . Neuron-specific enolase and S-100 levels increased in the ensuing 4 hrs post resuscitation in both groups , but they were significantly elevated in animals treated with the sham valve ( p < .01 ) . At 48 hrs , neurologic alertness score was significantly better in animals treated with the active valve ( 79.1 ± 18.7 vs. 50 ± 10 , p < .05 ) and was strongly negatively correlated with 1- and 4-hr postresuscitation neuron-specific enolase ( r = −.86 , p < .001 and r = −.87 , p < .001 , respectively ) and S-100 ( r = −.77 , p < .001 and r = −0.8 , p = .001 ) values . Conclusions : In this model of asphyxial cardiac arrest , intermittent airway occlusion with the impedance threshold device during the decompression phase of active compression-decompression cardiopulmonary resuscitation significantly improved hemodynamic parameters , 24- and 48-hr survival , and neurologic outcome evaluated both with clinical and biochemical parameters ( neuron-specific enolase , S-100 ) Abstract While therapeutic hypothermia improves the outcomes of individuals in cardiac arrest , the hemodynamic responses and mechanisms which underlie hypothermia-induced cardioprotection are not fully understood . Therefore , we investigated the mechanism by which induced hypothermia preserves cardiac function and protects against mitochondrial damage following cardiac arrest . Cardiac arrest was induced in adult male Wistar rats by asphyxiation for 8.5 min . Following resuscitation , the animals were r and omly assigned to a hypothermia ( 32 ° C ) or normothermia ( 37 ° C ) group . Monitoring results showed that cardiac output at the fourth hour after resuscitation was significantly better in rats treated with hypothermia when compared to rats treated with normothermia ( P < 0.01 ) . Examinations by transmission electron microscopy showed that mitochondria in the left ventricle of rats in the hypothermia group were significantly less swollen compared to such mitochondria in the normothermia group ( P < 0.001 ) . Additionally , opening of mitochondrial permeability transition pores occurred less frequently in the hypothermic group . While complex I/III activity in the electron transport reaction was damaged after cardiac arrest and resuscitation , the degree of injury was ameliorated by hypothermia treatment ( P < 0.05 ) . The amount of STAT-3 phosphorylated at tyrosine 705 and its expression in mitochondria were significantly higher under hypothermia treatment compared to normothermia treatment . In vitro studies showed that inhibition STAT-3 activation abolished the ability of hypothermia to protect H9C2 cardiomyocytes against injury produced by simulated ischemia and reperfusion . Therapeutic hypothermia treatment can ameliorate cardiac dysfunction and help preserve both mitochondrial integrity and electron transport activity BACKGROUND Previous research has demonstrated significant relationships between peri-shock pause and survival to discharge from out-of-hospital shockable cardiac arrest ( OHCA ) . OBJECTIVE To determine the impact of peri-shock pause on survival from OHCA during the ROC PRIMED r and omized controlled trial . METHODS We included patients in the ROC PRIMED trial who suffered OHCA between June 2007 and November 2009 , presented with a shockable rhythm and had CPR process data for at least one shock . We used multivariable logistic regression to determine the association between peri-shock pause duration and survival to hospital discharge . RESULTS Among 2006 patients studied , the median ( IQR ) shock pause duration was : pre-shock pause 15s ( 8 , 22 ) ; post-shock pause 6s ( 4 , 9 ) ; and peri-shock pause 22.0 s ( 14 , 31 ) . After adjusting for Utstein predictors of survival as well as CPR quality measures , the odds of survival to hospital discharge were significantly higher for patients with pre-shock pause < 10s ( OR : 1.52 , 95 % CI : 1.09 , 2.11 ) and peri-shock pause < 20s ( OR : 1.82 , 95 % CI : 1.17 , 2.85 ) when compared to patients with pre-shock pause ≥ 20s and peri-shock pause ≥ 40s . Post-shock pause was not significantly associated with survival to hospital discharge . Results for neurologically intact survival ( Modified Rankin Score ≤ 3 ) were similar to our primary outcome . CONCLUSIONS In patients with cardiac arrest presenting in a shockable rhythm during the ROC PRIMED trial , shorter pre- and peri-shock pauses were significantly associated with higher odds of survival . Future cardiopulmonary education and technology should focus on minimizing all peri-shock pauses IMPORTANCE It is unclear whether advanced airway management such as endotracheal intubation or use of supraglottic airway devices in the prehospital setting improves outcomes following out-of-hospital cardiac arrest ( OHCA ) compared with conventional bag-valve-mask ventilation . OBJECTIVE To test the hypothesis that prehospital advanced airway management is associated with favorable outcome after adult OHCA . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , nationwide , population -based study ( All-Japan Utstein Registry ) involving 649,654 consecutive adult patients in Japan who had an OHCA and in whom resuscitation was attempted by emergency responders with subsequent transport to medical institutions from January 2005 through December 2010 . MAIN OUTCOME MEASURES Favorable neurological outcome 1 month after an OHCA , defined as cerebral performance category 1 or 2 . RESULTS Of the eligible 649,359 patients with OHCA , 367,837 ( 57 % ) underwent bag-valve-mask ventilation and 281,522 ( 43 % ) advanced airway management , including 41,972 ( 6 % ) with endotracheal intubation and 239,550 ( 37 % ) with use of supraglottic airways . In the full cohort , the advanced airway group incurred a lower rate of favorable neurological outcome compared with the bag-valve-mask group ( 1.1 % vs 2.9 % ; odds ratio [ OR ] , 0.38 ; 95 % CI , 0.36 - 0.39 ) . In multivariable logistic regression , advanced airway management had an OR for favorable neurological outcome of 0.38 ( 95 % CI , 0.37 - 0.40 ) after adjusting for age , sex , etiology of arrest , first documented rhythm , witnessed status , type of byst and er cardiopulmonary resuscitation , use of public access automated external defibrillator , epinephrine administration , and time intervals . Similarly , the odds of neurologically favorable survival were significantly lower both for endotracheal intubation ( adjusted OR , 0.41 ; 95 % CI , 0.37 - 0.45 ) and for supraglottic airways ( adjusted OR , 0.38 ; 95 % CI , 0.36 - 0.40 ) . In a propensity score-matched cohort ( 357,228 patients ) , the adjusted odds of neurologically favorable survival were significantly lower both for endotracheal intubation ( adjusted OR , 0.45 ; 95 % CI , 0.37 - 0.55 ) and for use of supraglottic airways ( adjusted OR , 0.36 ; 95 % CI , 0.33 - 0.39 ) . Both endotracheal intubation and use of supraglottic airways were similarly associated with decreased odds of neurologically favorable survival . CONCLUSION AND RELEVANCE Among adult patients with OHCA , any type of advanced airway management was independently associated with decreased odds of neurologically favorable survival compared with conventional bag-valve-mask ventilation OBJECT To examine the efficacy of a new method of cardiac resuscitation , active compression-decompression cardiopulmonary resuscitation ( ACD CPR ) , in prehospital cardiac arrest . DESIGN Prospect i ve , r and omized , controlled trial . SETTING Physician-manned Mobile Intensive Care Unit ( MICU ) of a university hospital , serving a population of 200,000 . PARTICIPANTS Adult patients with prehospital nontraumatic cardiac arrest treated by the MICU . INTERVENTIONS Patients were r and omized to st and ard chest compression according to American Heart Association ( AHA ) recommendations ( group 1 , 30 patients ) or to the new technique ( group 2 , 26 patients ) . ACD was performed by use of a h and -held suction device . In both groups , advanced life support was performed as recommended by the AHA . MEASUREMENTS AND MAIN RESULTS Rate of patients regaining a spontaneous circulation ( ROSC ) , hospital discharge rate , and mean carbon dioxide content during resuscitation were recorded . ROSC rates in groups 1 and 2 were 40 % and 38.5 % , respectively . Four patients ( 13.3 % ) in group 1 and three patients ( 11.5 % ) in group 2 were discharged ( group 1 v group 2 : n.s . ) . Anatomic conditions precluded the application of ACD CPR in 5 patients . The new technique was found to impose greater physical efforts than STD CPR . Capnography was performed in 23 patients ( mean value : STD CPR : 11.9 + /- 4.7 mmHg , ACD CPR : 13.7 + /- 4.9 mmHg [ n.s . ] ) . CONCLUSIONS ACD CPR did not improve , outcome and practical performance was complicated . Therefore , this technique should not be performed routinely , or without strict supervision in prehospital cardiac arrest Background —Active compression-decompression ( ACD ) CPR combined with an inspiratory impedance threshold device ( ITD ) improves vital organ blood flow during cardiac arrest . This study compared survival rates with ACD+ITD CPR versus st and ard manual CPR ( S-CPR ) . Methods and Results —A prospect i ve , controlled trial was performed in Mainz , Germany , in which a 2-tiered emergency response included early defibrillation . Patients with out-of-hospital arrest of presumed cardiac pathogenesis were sequentially r and omized to ACD+ITD CPR or S-CPR by the advanced life support team after intubation . Rescuers learned which method of CPR to use at the start of each work shift . The primary end point was 1-hour survival after a witnessed arrest . With ACD+ITD CPR ( n=103 ) , return of spontaneous circulation and 1- and 24-hour survival rates were 55 % , 51 % , and 37 % versus 37 % , 32 % , and 22 % with S-CPR ( n=107 ) ( P = 0.016 , 0.006 , and 0.033 , respectively ) . One- and 24-hour survival rates in witnessed arrests were 55 % and 41 % with ACD+ITD CPR versus 33 % and 23 % in control subjects ( P = 0.011 and 0.019 ) , respectively . One- and 24-hour survival rates in patients with a witnessed arrest in ventricular fibrillation were 68 % and 58 % after ACD+ITD CPR versus 27 % and 23 % after S-CPR ( P = 0.002 and 0.009 ) , respectively . Patients r and omized ≥10 minutes after the call for help to the ACD+ITD CPR had a 3 times higher 1-hour survival rate than control subjects ( P = 0.002 ) . Hospital discharge rates were 18 % after ACD+ITD CPR versus 13 % in control subjects ( P = 0.41 ) . In witnessed arrests , overall neurological function trended higher with ACD+ITD CPR versus control subjects ( P = 0.07 ) . Conclusions —Compared with S-CPR , ACD+ITD CPR significantly improved short-term survival rates for patients with out-of-hospital cardiac arrest . Additional studies are needed to evaluate potential long-term benefits of ACD+ITD CPR BACKGROUND This study was design ed to assess the effects of a modified cardiopulmonary resuscitation ( CPR ) technique that consists of both active compression and active decompression of the chest ( ACD CPR ) versus st and ard CPR ( STD CPR ) on myocardial and cerebral blood flow during ventricular fibrillation both before and after epinephrine administration . METHODS AND RESULTS During a 30-second period of ventricular fibrillation cardiac arrest , 14 pigs were r and omized to receive either STD CPR ( n = 7 ) or ACD CPR ( n = 7 ) . Both STD and ACD CPR were performed using an automated pneumatic piston device applied midsternum , design ed to provide either active chest compression ( 1.5 to 2.0 in . ) and decompression or only active compression of the chest at 80 compressions per minute and 50 % duty cycle . Using radiolabeled microspheres , median total myocardial blood flow after 5 minutes of ventricular fibrillation was 14 ( 7 to 30 , minimum to maximum ) STD CPR versus 30 ( 9 to 46 ) mL.min-1 x 100 g-1 with ACD CPR ( P < .05 ) . Median cerebral blood flow was 15 ( 10 to 26 ) mL.min-1 x 100 g-1 with STD CPR and 30 ( 21 to 39 ) with ACD CPR ( P < .01 ) . When comparing STD with ACD CPR , aortic systolic ( 62 mm Hg [ 48 to 70 ] vs 80 [ 59 to 86 ] ) and diastolic ( 22 [ 18 to 28 ] vs 28 [ 21 to 36 ] ) pressures , calculated coronary systolic ( 30 [ 22 to 36 ] vs 49 [ 37 to 56 ] ) and diastolic ( 18 [ 16 to 23 ] vs 26 [ 21 to 31 ] ) perfusion pressures , end-tidal CO2 ( 1.4 % [ 0.8 to 1.8 ] vs 2.1 ( 1.8 to 2.4 ] ) , cerebral O2 delivery ( 3.1 mL.min-1 x 100 g-1 [ 1.5 to 4.5 ] vs 5.3 [ 3.8 to 7.5 ] ) , and cerebral perfusion pressure ( 14 mm Hg [ 4 to 22 ] vs 26 [ 6 to 34 ] ) were all significantly higher with ACD CPR : To compare these parameters before and after vasopressor therapy , a bolus of high-dose epinephrine ( 0.2 mg/kg ) was given to all animals after 5 minutes of ventricular fibrillation . Organ blood flow and calculated perfusion pressures increased significantly in both the STD and ACD groups after epinephrine . The differences observed between STD and ACD CPR before epinephrine were diminished 90 seconds after epinephrine but were again statistically significant when assessed 5 minutes later , once the acute effects of epinephrine had decreased . No difference in short-term resuscitation success was found between the two groups . CONCLUSIONS We conclude that ACD CPR significantly increases myocardial and cerebral blood flow during cardiac arrest in the absence of vasopressor therapy compared with STD CPR Background —This study evaluated the potential for an inspiratory impedance threshold valve ( ITV ) to improve 24-hour survival and neurological function in a pig model of cardiac arrest . Methods and Results —Using a r and omized , prospect i ve , and blinded design , we compared the effects of a sham versus active ITV on 24-hour survival and neurological function . After 6 minutes of ventricular fibrillation ( VF ) , followed by 6 minutes of cardiopulmonary resuscitation ( CPR ) with either a sham or an active valve , anesthetized pigs received 3 sequential 200-J shocks . If VF persisted , they received epinephrine ( 0.045 mg/kg ) , 90 seconds of CPR , and 3 more 200-J shocks . A total of 11 of 20 pigs ( 55 % ) in the sham versus 17 of 20 ( 85 % ) in the active valve group survived for 24 hours ( P < 0.05 ) . Neurological scores were significantly higher with the active valve ; the cerebral performance score ( 1=normal , 5=brain death ) was 2.2±0.2 with the sham ITV versus 1.4±0.2 with the active valve ( P < 0.05 ) . A total of 1 of 11 in the sham versus 12 of 17 in the active valve group had completely normal neurological function ( P < 0.05 ) . Peak end-tidal CO2 ( Petco2 ) values were significantly higher with the active valve ( 20.4±1.0 ) than the sham ( 16.8±1.5 ) ( P < 0.05 ) . Petco2 > 18 mm Hg correlated with increased survival ( P < 0.05 ) . Conclusions —Use of a functional ITV during st and ard CPR significantly improved 24-hour survival rates and neurological recovery . Petco2 and systolic blood pressure were also significantly higher in the active valve group . These data support further evaluation of ITV during st and ard CPR This prospect i ve , controlled trial with crossover group design compares the effectiveness of active compression-decompression ( ACD ) cardiopulmonary resuscitation ( CPR ) and st and ard CPR on the outcomes of victims of prehospital cardiac arrest . In three UK cities , victims of non-traumatic , out of hospital cardiac arrest , over the age of 8 years received either st and ard or ACD-CPR on arrival of ambulance personnel . Main outcome measures were return of spontaneous circulation , survival to be admitted to the intensive care unit , survival to hospital discharge , and neurological outcome . A total of 576 patients ( STD-CPR , n=309 ; ACD-CPR , n=267 ) were analysed . The treatment groups were similar with respect to age , gender , proportion of witnessed arrests , initial cardiac rhythm , and call to advanced life support interval . The proportion of patients receiving byst and er CPR was higher in the ACD group ( 37.1 % vs. 28.5 % ; P=0.028 ) . The interval between collapse and defibrillation was longer in the ACD group ( 12.3 min vs. 10.4 min ; P=0.028 ) . There was no difference between the STD-CPR and ACD-CPR groups in survival to admission to the intensive care unit ( 13.6 % vs. 13.8 % ; P=0.93 ) or hospital discharge ( 4.8 % vs. 6.0 % ; P=0.67 ) . There was no difference between the groups with respect to the neurological outcome of those patients surviving to hospital discharge . Analysis of important subgroups also showed no benefit for ACD-CPR . We conclude that there was no improvement in outcome with ACD-CPR when used by ambulance personnel in Cardiff and Portsmouth Objective : To determine whether an impedance threshold device , design ed to enhance circulation , would increase acute resuscitation rates for patients in cardiac arrest receiving conventional manual cardiopulmonary resuscitation . Design : Prospect i ve , r and omized , double-blind , intention-to-treat . Setting : Out-of-hospital trial conducted in the Milwaukee , WI , emergency medical services system . Patients : Adults in cardiac arrest of presumed cardiac etiology . Interventions : On arrival of advanced life support , patients were treated with st and ard cardiopulmonary resuscitation combined with either an active or a sham impedance threshold device . Measurements and Main Results : We measured safety and efficacy of the impedance threshold device ; the primary end point was intensive care unit admission . Statistical analyses performed included the chi-square test and multivariate regression analysis . One hundred sixteen patients were treated with a sham impedance threshold device , and 114 patients were treated with an active impedance threshold device . Overall intensive care unit admission rates were 17 % with the sham device vs. 25 % in the active impedance threshold device ( p = .13 ; odds ratio , 1.64 ; 95 % confidence interval , 0.87 , 3.10 ) . Patients in the subgroup presenting with pulseless electrical activity had intensive care unit admission and 24-hr survival rates of 20 % and 12 % in sham ( n = 25 ) vs. 52 % and 30 % in active impedance threshold device groups ( n = 27 ) ( p = .018 , odds ratio , 4.31 ; 95 % confidence interval , 1.28 , 14.5 , and p = .12 , odds ratio , 3.09 ; 95 % confidence interval , 0.74 , 13.0 , respectively ) . A post hoc analysis of patients with pulseless electrical activity at any time during the cardiac arrest revealed that intensive care unit and 24-hr survival rates were 20 % and 11 % in the sham ( n = 56 ) vs. 41 % and 27 % in the active impedance threshold device groups ( n = 49 ) ( p = .018 , odds ratio , 2.82 ; 95 % confidence interval , 1.19 , 6.67 , and p = .037 , odds ratio , 3.01 ; 95 % confidence interval , 1.07 , 8.96 , respectively ) . There were no statistically significant differences in outcomes for patients presenting in ventricular fibrillation and asystole . Adverse event and complication rates were also similar . Conclusions : During this first clinical trial of the impedance threshold device during st and ard cardiopulmonary resuscitation , use of the new device more than doubled short-term survival rates in patients presenting with pulseless electrical activity . A larger clinical trial is underway to determine the potential longer term benefits of the impedance threshold device in cardiac arrest BACKGROUND The impedance threshold device ( ITD ) is design ed to enhance venous return and cardiac output during cardiopulmonary resuscitation ( CPR ) by increasing the degree of negative intrathoracic pressure . Previous studies have suggested that the use of an ITD during CPR may improve survival rates after cardiac arrest . METHODS We compared the use of an active ITD with that of a sham ITD in patients with out-of-hospital cardiac arrest who underwent st and ard CPR at 10 sites in the United States and Canada . Patients , investigators , study coordinators , and all care providers were unaware of the treatment assignments . The primary outcome was survival to hospital discharge with satisfactory function ( i.e. , a score of ≤3 on the modified Rankin scale , which ranges from 0 to 6 , with higher scores indicating greater disability ) . RESULTS Of 8718 patients included in the analysis , 4345 were r and omly assigned to treatment with a sham ITD and 4373 to treatment with an active device . A total of 260 patients ( 6.0 % ) in the sham-ITD group and 254 patients ( 5.8 % ) in the active-ITD group met the primary outcome ( risk difference adjusted for sequential monitoring , -0.1 percentage points ; 95 % confidence interval , -1.1 to 0.8 ; P=0.71 ) . There were also no significant differences in the secondary outcomes , including rates of return of spontaneous circulation on arrival at the emergency department , survival to hospital admission , and survival to hospital discharge . CONCLUSIONS Use of the ITD did not significantly improve survival with satisfactory function among patients with out-of-hospital cardiac arrest receiving st and ard CPR . ( Funded by the National Heart , Lung , and Blood Institute and others ; ROC PRIMED Clinical Trials.gov number , NCT00394706 . ) CONTEXT The health and policy implication s of regional variation in incidence and outcome of out-of-hospital cardiac arrest remain to be determined . OBJECTIVE To evaluate whether cardiac arrest incidence and outcome differ across geographic regions . DESIGN , SETTING , AND PATIENTS Prospect i ve observational study ( the Resuscitation Outcomes Consortium ) of all out-of-hospital cardiac arrests in 10 North American sites ( 8 US and 2 Canadian ) from May 1 , 2006 , to April 30 , 2007 , followed up to hospital discharge , and including data available as of June 28 , 2008 . Cases ( aged 0 - 108 years ) were assessed by organized emergency medical services ( EMS ) personnel , did not have traumatic injury , and received attempts at external defibrillation or chest compressions or resuscitation was not attempted . Census data were used to determine rates adjusted for age and sex . MAIN OUTCOME MEASURES Incidence rate , mortality rate , case-fatality rate , and survival to discharge for patients assessed or treated by EMS personnel or with an initial rhythm of ventricular fibrillation . RESULTS Among the 10 sites , the total catchment population was 21.4 million , and there were 20,520 cardiac arrests . A total of 11,898 ( 58.0 % ) had resuscitation attempted ; 2729 ( 22.9 % of treated ) had initial rhythm of ventricular fibrillation or ventricular tachycardia or rhythms that were shockable by an automated external defibrillator ; and 954 ( 4.6 % of total ) were discharged alive . The median incidence of EMS-treated cardiac arrest across sites was 52.1 ( interquartile range [ IQR ] , 48.0 - 70.1 ) per 100,000 population ; survival ranged from 3.0 % to 16.3 % , with a median of 8.4 % ( IQR , 5.4%-10.4 % ) . Median ventricular fibrillation incidence was 12.6 ( IQR , 10.6 - 5.2 ) per 100,000 population ; survival ranged from 7.7 % to 39.9 % , with a median of 22.0 % ( IQR , 15.0%-24.4 % ) , with significant differences across sites for incidence and survival ( P<.001 ) . CONCLUSION In this study involving 10 geographic regions in North America , there were significant and important regional differences in out-of-hospital cardiac arrest incidence and outcome OBJECTIVE --Active compression-decompression ( ACD ) cardiopulmonary resuscitation ( CPR ) appears to improve ventilation and coronary perfusion when compared with st and ard CPR . The objective was to evaluate potential benefits of this new CPR technique in patients with out-of-hospital cardiac arrest in St Paul , Minn. DESIGN --Ten-month , prospect i ve , r and omized parallel-group design . SETTING --St Paul , Minn , population 270,000 . PATIENTS --All normothermic victims of nontraumatic cardiac arrest older than 8 years who received CPR . MAIN OUTCOME MEASURES --Return of spontaneous circulation , admission to the intensive care unit ( ICU ) , return of baseline neurological function ( alert and oriented to person , place , and time ) , survival to hospital discharge , survival to hospital discharge with return of baseline neurological function , and complications . RESULTS --Seventy-seven patients received st and ard CPR and 53 patients received ACD CPR . The mean emergency medical services call response interval was less than 3.5 minutes . When all patients were considered , a higher percentage of ACD CPR patients had a return of spontaneous circulation and were admitted to the ICU vs st and ard CPR ( 45 % vs 31 % , and 40 % vs 26 % , respectively ) , but these trends were not statistically significant ( P < .10 and P < .10 ) . No statistically significant differences were found between hospital discharge rates ( 12 [ 23 % ] of 53 for ACD CPR vs 13 [ 17 % ] of 77 for st and ard CPR ) , return to baseline neurological function ( 10 [ 19 % ] of 53 for ACD CPR vs 13 [ 17 % ] of 77 for st and ard CPR ) , or return to baseline neurological function at hospital discharge ( nine [ 17 % ] of 53 for ACD CPR vs 12 [ 16 % ] of 77 for st and ard CPR ) . Return of spontaneous circulation , ICU admission , and neurological recovery in both CPR groups were highly correlated with downtime ( time from collapse to emergency medical system personnel arrival to the scene in witnessed arrests ) . With less than 10 minutes ' downtime , survival to the ICU was 59 % ( 19/32 ) with ACD CPR and 33 % ( 16/49 ) with st and ard CPR ( P < .02 ) , return to baseline neurological function was 31 % ( 10/32 ) with ACD CPR and 20 % ( 10/49 ) with st and ard CPR ( P = .27 ) , and hospital discharge rate was 38 % ( 12/32 ) with ACD CPR and 20 % ( 10/49 ) with st and ard CPR ( P = .17 ) . Complication rates in patients admitted to the hospital were similar in both groups . CONCLUSIONS --This study demonstrates that ACD CPR appears to be more effective than st and ard CPR in a well-defined subset of victims of out-of-hospital cardiac arrest during the critical early phases of resuscitation . Based on this study , a larger study should be performed to evaluate the potential long-term benefits of ACD CPR Tracheal intubation ( ETI ) is considered the method of choice for securing the airway and for providing effective ventilation during cardiac arrest . However , ETI requires skills which are difficult to maintain especially if practised infrequently . The laryngeal tube ( LT ) has been successfully tested and used in anaesthesia and in simulated cardiac arrest in manikins . To compare the initiation and success of ventilation with the LT , ETI and bag-valve mask ( BVM ) in a cardiac arrest scenario , 60 fire-fighter emergency medical technician ( EMT ) students formed teams of two rescuers at r and om and were allocated to use these devices . We found that the teams using the LT were able to initiate ventilation more rapidly than those performing ETI ( P < 0.0001 ) . The LT and ETI provided equal minute volumes of ventilation , which was significantly higher than that delivered with the BVM ( P < 0.0001 ) . Our data suggest that the LT may enable airway control more rapidly and as effectively as ETI , and compared to BVM , may provide better minute ventilation when used by inexperienced personnel Improved cardiopulmonary circulation with active compression-decompression cardiopulmonary resuscitation ( ACD-CPR ) has been demonstrated in studies using different animal models and a small number of humans in cardiac arrest ( CA ) . However , prehospital studies have shown both positive and no extra benefit of ACD-CPR on return of spontaneous circulation ( ROSC ) , hospital admission and discharge rates . The aim of our prospect i ve study was to compare st and ard manual CPR ( S-CPR ) with ACD-CPR as the initial technique of resuscitating patients with out-of-hospital CA , with respect to survival rates and neurological outcome . Patients with out-of-hospital CA treated by emergency medical services ( EMS ) personnel were r and omly assigned to one of two groups ( ACD-CPR versus S-CPR ) . Time intervals to key measures were documented by means of on-line tape-recording . Neurological outcome was assessed using st and ard scoring systems ( cerebral and overall performance categories ( CPC and OPC ) ) . A total of 220 patients ( S-CPR , n = 114 : ACD-CPR , n = 106 ) were included in the study in a r and om order . The treatment groups were similar with respect to age , sex , time interval from collapse to CPR , defibrillation and first adrenaline medication . There was no difference between the ACD group and the st and ard CPR group in terms of ROSC ( 50.9 % vs. 59.6 % ) , hospital admission ( 33 % vs. 33.3 % ) , hospital discharge ( 16 % vs. 14 % ) , or CPC and OPC ( 1.82 vs. 2.13 and 2.06 vs. 2.25 , respectively ) . Concerning complications of CPR , there was no difference between the groups . In our two-tiered EMS system with physician-staffed ambulances , ACD-CPR neither improved nor impaired survival rates and neurological prognosis in patients with out-of-hospital cardiac arrest . The new CPR technique did not increase the complications associated with the resuscitation effort BACKGROUND The basic premise that frequent ventilations during cardiopulmonary resuscitation ( CPR ) are a necessity for tissue oxygenation has recently been challenged . An inspiratory impedance threshold device ( ITD ) recently has also been shown to increase CPR efficiency , principally by augmenting circulation with little impact on ventilation . The optimal compression to ventilation ( C/V ) is not known for this new device . The purpose of this study was to compare the currently recommended C/V ratio of 5:1 with a 10:1 ratio , + /- the ITD , to optimize circulation and oxygenation during CPR . METHODS Thirty-two adult pigs weighing 26 - 31 kg were r and omized to CPR with varying C/V ratios + /- the ITD as follows : A = 5:1 , B = 5:1+ITD , C = 10:1 , D = 10:1+ITD . After 6 min of untreated ventricular fibrillation ( VF ) , closed-chest st and ard CPR was performed with an automatic piston device that does not impede passive chest wall recoil , at a continuous compression rate of 100 min(-1 ) . Synchronous breaths were given every 5 or 10 compressions during the decompression phase depending on the group . CPR was performed for 6 min and physiological variables were measured throughout the experimental protocol . RESULTS A reduction in the frequency of ventilation from 5:1 to 10:1 result ed in significantly improved arterial and coronary perfusion pressure in a pig model of cardiac arrest . Addition of an ITD result ed in further increases in arterial and coronary perfusion pressures with both 5:1 and 10:1 C/V ratios , without compromising oxygenation . CONCLUSION CPR efficiency can be optimized by changing the compression : ventilation ratio from 5:1 to 10:1 and with concurrent use of the inspiratory threshold device BACKGROUND A recent out-of-hospital cardiac arrest ( OHCA ) clinical trial showed improved survival to hospital discharge ( HD ) with favorable neurologic function for patients with cardiac arrest of cardiac origin treated with active compression decompression cardiopulmonary resuscitation ( CPR ) plus an impedance threshold device ( ACD+ICD ) versus st and ard ( S ) CPR . The current analysis examined whether treatment with ACD+ITD is more effective than st and ard ( S-CPR ) for all cardiac arrests of non-traumatic origin , regardless of the etiology . METHODS This is a secondary analysis of data from a r and omized , prospect i ve , multicenter , intention-to-treat , OHCA clinical trial . Adults with presumed non-traumatic cardiac arrest were enrolled and followed for one year post arrest . The primary endpoint was survival to hospital discharge ( HD ) with favorable neurologic function ( Modified Rankin Scale score ≤ 3 ) . RESULTS Between October 2005 and July 2009 , 2738 patients were enrolled ( S-CPR=1335 ; ACD+ITD=1403 ) . Survival to HD with favorable neurologic function was greater with ACD+ITD compared with S-CPR : 7.9 % versus 5.7 % , ( OR 1.42 , 95 % CI 1.04 , 1.95 , p=0.027 ) . One-year survival was also greater : 7.9 % versus 5.7 % , ( OR 1.43 , 95 % CI 1.04 , 1.96 , p=0.026 ) . Nearly all survivors in both groups had returned to their baseline neurological function by one year . Major adverse event rates were similar between groups . CONCLUSIONS Treatment of out-of-hospital non-traumatic cardiac arrest patients with ACD+ITD result ed in a significant increase in survival to hospital discharge with favorable neurological function when compared with S-CPR . A significant increase survival rates was observed up to one year after arrest in subjects treated with ACD+ITD , regardless of the etiology of the cardiac arrest BACKGROUND In animals in cardiac arrest , an inspiratory impedance threshold device ( ITD ) has been shown to improve hemodynamics and neurologically intact survival . The objective of this study was to determine whether an ITD would improve blood pressure ( BP ) in patients receiving CPR for out-of-hospital cardiac arrest . METHODS This prospect i ve , r and omized , double-blind , intention-to-treat study was conducted in the Milwaukee , WI , emergency medical services ( EMS ) system . EMS personnel used an active ( functional ) or sham ( non-functional ) ITD on a tracheal tube on adults in cardiac arrest of presumed cardiac etiology . Care between groups was similar except for ITD type . Low dose epinephrine ( 1 mg ) was used per American Heart Association Guidelines . Femoral arterial BP ( mmHg ) was measured invasively during CPR . RESULTS Mean+/-S.D. time from ITD placement to first invasive BP recording was approximately 14 min . Twelve patients were treated with a sham ITD versus 10 patients with an active ITD . Systolic BPs ( mean+/-S.D. ) [ number of patients treated at given time point ] at T = 0 ( time of first arterial BP measurement ) , and T=2 , 5 and 7 min were 85+/-29 [ 10 ] , 85+/-23 [ 10 ] , 85+/-16 [ 9 ] and 69+/-22 [ 8 ] in the group receiving an active ITD compared with 43+/-15 [ 12 ] , 47+/-16 [ 12 ] , 47+/-20 [ 9 ] , and 52+/-23 [ 9 ] in subjects treated with a sham ITD , respectively ( p < 0.01 for all times ) . Diastolic BPs at T = 0 , 2 , 5 and 7 min were 20+/-12 , 21+/-13 , 23+/-15 and 25+/-14 in the group receiving an active ITD compared with 15+/-9 , 17+/-8 , 17+/-9 and 19+/-8 in subjects treated with a sham ITD , respectively ( p = NS for all times ) . No significant adverse device events were reported . CONCLUSIONS Use of the active ITD was found to increase systolic pressures safely and significantly in patients in cardiac arrest compared with sham controls OBJECTIVE To compare the impact of active compression-decompression ( ACD ) cardiopulmonary resuscitation ( CPR ) and st and ard CPR on the outcomes of in-hospital and prehospital victims of cardiac arrest . DESIGN R and omized controlled trial with blinding of allocation using a sealed container . SETTING S ( 1 ) Emergency departments , wards , and intensive care units of 5 university hospitals and ( 2 ) all locations outside hospitals in 2 midsized cities . PATIENTS A total of 1784 adults who had cardiac arrest . INTERVENTION Patients received either st and ard or ACD CPR throughout resuscitation . MAIN OUTCOME MEASURES Survival for 1 hour and to hospital discharge and the modified Mini-Mental State Examination ( MMSE ) . RESULTS All characteristics were similar in the st and ard and ACD CPR groups for the 773 in-hospital patients and the 1011 prehospital patients . For in-hospital patients , there were no significant differences between the st and ard ( n = 368 ) and ACD ( n = 405 ) CPR groups in survival for 1 hour ( 35.1 % vs 34.6 % ; P = .89 ) , in survival until hospital discharge ( 11.4 % vs 10.4 % ; P = .64 ) , or in the median MMSE score of survivors ( 37 in both groups ) . For patients who collapsed outside the hospital , there were also no significant differences between the st and ard ( n = 510 ) and ACD ( n = 501 ) CPR groups in survival for 1 hour ( 16.5 % vs 18.2 % ; P = .48 ) , in survival to hospital discharge ( 3.7 % vs 4.6 % ; P = .49 ) , or in the median MMSE score of survivors ( 35 in both groups ) . Exploration of clinical ly important subgroups failed to identify any patients who appeared to benefit from ACD CPR . CONCLUSIONS ACD CPR did not improve survival or neurologic outcomes in any group of patients with cardiac arrest Different mechanical devices have been developed to improve cardiopulmonary resuscitation ( CPR ) . The aim of this study was to evaluate active compression-decompression ( ACD ) CPR applied by Emergency Medical Service ( EMS ) in a defined population . The Trondheim region EMS ( population 154,000 ) employs simultaneous paramedic and physician response . Upon decision to treat , patients with cardiac arrest of presumed cardiac origin were allocated to ACD CPR ( CardioPump ) or st and ard CPR by drawing a r and om number tag . Outcome in each patient was determined on a 5 point ordinal scale ( no clinical improvement = 1 , survival to discharge = 5 ) . In 4 years , CPR was attempted in a total of 431 cardiac arrests , 54 patients ( 13 % ) survived to discharge ; 302 patients with similar baseline characteristics were r and omised . The prevalence of byst and er CPR was 57 % and the median call-arrival interval 9 min . By intention to treat , the mean score in the st and ard CPR group was 2.51 and 17/145 patients ( 12 % ) survived . The mean score in the ACD CPR group was 2.53 ( P = 0.9 ) and 20/157 patients ( 13 % ) survived . Cerebral outcome was similar in the two groups . Among the 145 ACD patients , the technique was successfully applied in 110 , found inapplicable in 35 and in seven patients chest compressions were unnecessary . This is the largest , single-centre , r and omised , population based study of ACD CPR in out-of-hospital cardiac arrest to date . Even when considering a wider outcome spectrum than crude survival , we found no evidence of clinical benefit . In a quarter of cases ACD CPR was inapplicable , further limiting its potential usefulness BACKGROUND We previously observed that short-term survival after out-of-hospital cardiac arrest was greater with active compression-decompression cardiopulmonary resuscitation ( CPR ) than with st and ard CPR . In the current study , we assessed the effects of the active compression-decompression method on one-year survival . METHODS Patients who had cardiac arrest in the Paris metropolitan area or in Thionville , France , more than 80 percent of whom had asystole , were assigned to receive either st and ard CPR ( 377 patients ) or active compression-decompression CPR ( 373 patients ) according to whether their arrest occurred on an even or odd day of the month , respectively . The primary end point was survival at one year . The rate of survival to hospital discharge without neurologic impairment and the neurologic outcome were secondary end points . RESULTS Both the rate of hospital discharge without neurologic impairment ( 6 percent vs. 2 percent , P=0.01 ) and the one-year survival rate ( 5 percent vs. 2 percent , P=0.03 ) were significantly higher among patients who received active compression-decompression CPR than among those who received st and ard CPR . All patients who survived to one year had cardiac arrests that were witnessed . Nine of 17 one-year survivors in the active compression-decompression group and 2 of 7 in the st and ard group , respectively , initially had asystole or pulseless electrical activity . In 12 of the 17 survivors who had received active compression-decompression CPR , neurologic status returned to base line , as compared with 3 of 7 survivors who had received st and ard CPR ( P=0.34 ) . CONCLUSIONS Active compression-decompression CPR performed during advanced life support significantly improved long-term survival rates among patients who had cardiac arrest outside the hospital OBJECTIVE To compare the effectiveness of active compression-decompression ( ACD ) cardiopulmonary resuscitation ( CPR ) with a h and held suction device vs st and ard manual CPR in victims of out-of-hospital cardiopulmonary arrest . DESIGN Prospect i ve r and omized clinical trial with crossover group design . SETTING Emergency medical services ( EMS ) of a large ( San Francisco ) and medium-sized ( Fresno ) city in California . PATIENTS All normothermic adult victims of out-of-hospital , nontraumatic cardiac arrest on whom CPR was performed by first responders . INTERVENTION Patients were r and omized to receive either st and ard manual CPR according to American Heart Association guidelines or ACD CPR , on first-responder contact . MAIN OUTCOME MEASURES Return of spontaneous circulation , admission to the intensive care unit , survival to hospital discharge , and neurological function at hospital discharge . RESULTS The ACD group ( n = 117 in Fresno ; n = 297 in San Francisco ) and st and ard group ( n = 136 in Fresno ; n = 310 in San Francisco ) were similar with regard to demographic and prognostic variables , such as age , witnessed arrest and byst and er CPR frequency , and initial cardiac rhythm . Average interval from 911 call activation to EMS responder arrival was 6.4 minutes in Fresno and 4.0 minutes in San Francisco . In Fresno , there was no difference between the ACD group and st and ard CPR group in return of spontaneous circulation ( 17 % vs 20 % ; P = .68 ) , hospital admission ( 16 % vs 20 % ; P = .56 ) , hospital discharge ( 5 % vs 7 % ; P = .64 ) , or cerebral performance category score at discharge ( 1.5 vs 1.6 ; P = .90 ) . Similarly , in San Francisco there was no difference between the ACD group and st and ard CPR group in return of spontaneous circulation ( 19 % vs 21 % ; P = .65 ) , hospital admission ( 13.5 % vs 14.5 % ; P = .79 ) , hospital discharge ( 4.7 % vs 5.5 % ; P = .80 ) , or cerebral performance category score at discharge ( 2.2 vs 2.6 ; P = .31 ) . There was no increase in significant complications associated with the use of ACD CPR . CONCLUSION There was no improvement in outcome with ACD CPR in out-of-hospital cardiac arrest in these two cities . Differences in study design , demographics , EMS systems , response intervals , training , and technique performance may contribute to the lack of improvement in initial resuscitation with ACD CPR compared with previous studies . Future research needs to control these variables to determine the reason for these differences in outcome Introduction : Use of an inspiratory impedance threshold device ( ITD ) significantly increases coronary perfusion pressures and survival in patients ventilated with an endotracheal tube ( ETT ) during active compression – decompression cardiopulmonary resuscitation . We tested the hypothesis that the ITD could lower intratracheal pressures when attached to either a facemask or ETT . Methods : An active and sham ITD were r and omly applied first to a facemask and then to an ETT during active compression-decompression cardiopulmonary resuscitation in 13 out-of-hospital cardiac arrest patients in a r and omized , double-blinded , prospect i ve clinical trial . The compression-to – bag-valve ventilation ratio was 15:2 . Airway pressures ( surrogate for intrathoracic pressure ) were measured with a pressure transducer . A sham and an active ITD were used for 1 min each in a r and omized order , first on a facemask and then on an ETT . Statistical analyses were made using Friedman 's and Wilcoxon 's rank-sum tests . Results : For the primary end point , mean ± sd maximum negative intrathoracic pressures ( mm Hg ) during the decompression phase of cardiopulmonary resuscitation were −1.0 ± 0.73 mm Hg with a sham vs. −4.6 ± 3.7 mm Hg with an active ITD on the facemask ( p = .003 ) and −1.3 ± 1.3 mm Hg with a sham ITD vs. −7.3 ± 4.5 mm Hg with an active ITD on an ETT ( p = .0009 ) . Decompression phase airway pressures with the facemask and ETT were not statistically different . Conclusions : Use of an active ITD attached to a facemask or an ETT result ed in a significantly lower negative intratracheal pressure during the decompression phase of active compression – decompression cardiopulmonary resuscitation when compared with controls . Airway pressures with an ITD on either a facemask or ETT were similar . The ITD – facemask combination was practical and enables rapid deployment of this life-saving technology OBJECTIVE Active compression-decompression ( ACD ) cardiopulmonary resuscitation ( CPR ) utilizes a h and -held suction device with a pressure gauge that enables the operator to compress as well as actively decompress the chest . This new CPR method improves hemodynamic and ventilatory parameters when compared with st and ard CPR . ACD-CPR is easy to perform but may be more labor intensive . The purpose of this study was to quantify and compare the work required to perform ACD and st and ard CPR . METHODS Cardiopulmonary testing was performed on six basic cardiac life support- and ACD-trained St. Paul , MN fire-fighter personnel during performance of 10 min each of ACD and st and ard CPR on a mannequin equipped with a compression gauge . The order of CPR techniques was determined r and omly with > 1 h between each study . Each CPR method was performed at 80 compressions/min ( timed with a metronome ) , to a depth of 1.5 - 2 inches , and with a 50 % duty cycle . RESULTS Baseline cardiopulmonary measurements were similar at rest prior to performance of both CPR methods . During st and ard and ACD-CPR , respectively , rate-pressure product was 18.2 + /- 3.0 vs. 23.8 + /- 1.7 ( x 1000 , P < 0.01 ) ; mean oxygen consumption 15.98 + /- 2.29 vs. 20.07 + /- 2.10 ml/kg/min or 4.6 + /- 0.7 vs. 5.7 + /- 0.6 METS ( P < 0.01 ) ; carbon dioxide production 1115.7 + /- 110 vs. 1459.1 + /- 176 ml/min ; respiratory exchange ratio 0.88 + /- 0.04 vs. 0.92 + /- 0.04 ( P = NS ) ; and minute ventilation 35.5 + /- 5.1 vs. 45.6 + /- 9.2 l/min ( P < 0.01 ) . CONCLUSIONS Approximately 25 % more work is required to perform ACD-CPR compared with st and ard CPR . Both methods require subanaerobic energy expenditure and can therefore be sustained for a sufficient length of time by most individuals to optimize resuscitation efforts . Due to the slightly higher work requirement , ACD-CPR may be more difficult to perform compared with st and ard CPR for long periods of time , particularly by individuals unaccustomed to the workload requirement of CPR , in general Background and Purpose : The purpose of this study was to examine the relationship between the Modified Rankin Scale ( MRS ) and poststroke recovery in neurological deficits , activities of daily living ( ADL ) , higher level of physical and social functioning and the patients ’ preference for health state . Methods : Four hundred and fifty-nine participants in the Kansas City Stroke Study were prospect ively assessed for measures of MRS , NIH Stroke Scale ( NIHSS ) , Barthel ADL , SF-36 physical functioning , SF-36 social functioning , and Time Trade-Off ( TTO ) . ANOVA and Bonferroni multiple comparisons were used to examine any differences in 3-month scores of NIHSS , Barthel ADL , SF-36 physical functioning , SF-36 social functioning and TTO between levels of the MRS . In addition , SF-36 physical functioning , SF-36 social functioning and TTO were characterized in patients who demonstrated improvement in global MRS outcome and also achieved a Barthel Index ( BI ) ≧95 at 3 months after stroke . Results : Two hundred and eighty patients ( 62 % ) shifted at least one grade in MRS from baseline to 3 months after stroke . Only 67 or 194 patients were considered to have a favorable outcome using MRS 0/1 or MRS 0/1/2 , respectively , as criteria . Mean 3-month NIHSS and Barthel ADL scores were not significantly different between Rankin 0/1 and 2 , but they were significantly different among Rankin 3 , 4 and 5 ( all p < 0.05 ) . Mean 3-month scores of physical functioning and SF-36 social functioning were significantly different among Rankin 0/1 , 2 , 3 and 4 ( all pairwise p < 0.05 ) . Proportions of patients who achieved NIHSS ≤1 or BI ≧95 decreased as MRS grade s worsened . In patients who showed improvement in MRS global outcome and also achieved BI ≧95 , mean scores on TTO were similar . Conclusions : Definition of favorable outcomes should include transition in the Modified Rankin score rather than MRS dichotomized as 0/1 or 0/1/2 because patients with transition in MRS scores have improvement in ADL , increased higher level of functioning and higher utility for health state BACKGROUND Active compression-decompression cardiopulmonary resuscitation ( CPR ) with decreased intrathoracic pressure in the decompression phase can lead to improved haemodynamics compared with st and ard CPR . We aim ed to assess effectiveness and safety of this intervention on survival with favourable neurological function after out-of-hospital cardiac arrest . METHODS In our r and omised trial of 46 emergency medical service agencies ( serving 2·3 million people ) in urban , suburban , and rural areas of the USA , we assessed outcomes for patients with out-of-hospital cardiac arrest according to Utstein guidelines . We provisionally enrolled patients to receive st and ard CPR or active compression-decompression CPR with augmented negative intrathoracic pressure ( via an impedance-threshold device ) with a computer-generated block r and omisation weekly schedule in a one-to-one ratio . Adults ( presumed age or age ≥18 years ) who had a non-traumatic arrest of presumed cardiac cause and met initial and final selection criteria received design ated CPR and were included in the final analyses . The primary endpoint was survival to hospital discharge with favourable neurological function ( modified Rankin scale score of ≤3 ) . All investigators apart from initial rescuers were masked to treatment group assignment . This trial is registered with Clinical Trials.gov , number NCT00189423 . FINDINGS 2470 provisionally enrolled patients were r and omly allocated to treatment groups . 813 ( 68 % ) of 1201 patients assigned to the st and ard CPR group ( controls ) and 840 ( 66 % ) of 1269 assigned to intervention CPR received design ated CPR and were included in the final analyses . 47 ( 6 % ) of 813 controls survived to hospital discharge with favourable neurological function compared with 75 ( 9 % ) of 840 patients in the intervention group ( odds ratio 1·58 , 95 % CI 1·07 - 2·36 ; p=0·019 ] . 74 ( 9 % ) of 840 patients survived to 1 year in the intervention group compared with 48 ( 6 % ) of 813 controls ( p=0·03 ) , with equivalent cognitive skills , disability ratings , and emotional-psychological statuses in both groups . The overall major adverse event rate did not differ between groups , but more patients had pulmonary oedema in the intervention group ( 94 [ 11 % ] of 840 ) than did controls ( 62 [ 7 % ] of 813 ; p=0·015 ) . INTERPRETATION On the basis of our findings showing increased effectiveness and generalisability of the study intervention , active compression-decompression CPR with augmentation of negative intrathoracic pressure should be considered as an alternative to st and ard CPR to increase long-term survival after cardiac arrest . FUNDING US National Institutes of Health grant R44-HL065851 - 03 , Advanced Circulatory Systems The use of an inspiratory impedance threshold valve ( ITV ) during cardiopulmonary resuscitation ( CPR ) should reduce intrathoracic pressure during natural chest recoil or active chest decompression . This might in turn improve venous return and thereby organ blood flow . The haemodynamic effects during both st and ard CPR and active compression-decompression (ACD)-CPR with and without the ITV , therefore , were studied in a well-established porcine model with cross-over design . Sixteen pigs were r and omised to one of four methods initially , changing the method every fifth minute during mechanical chest compression at 100 min(-1 ) . Myocardial blood flow was doubled when the valve was added to st and ard CPR , median ( q25-q75 ) 14 ( 3 - 47 ) versus 27 ( 9 - 51 ) ml min(-1 ) 100 g(-1 ) ( P=0.001 ) . ACD-CPR caused a similar increase , while adding the ITV to ACD-CPR only tended to increase myocardial blood flow ( P=0.077 ) . Varying the technique had no effect on cerebral , kidney or carotid blood flow , coronary perfusion pressure , expired CO(2 ) concentrations or blood gases . The valve is a promising new tool in CPR , but more independent studies of the device are needed In a prospect i ve r and omised study we investigated end-tidal carbon dioxide levels during st and ard versus active compression-decompression ( ACD ) cardiopulmonary resuscitation ( CPR ) assuming that the end-tital carbon dioxide reflects cardiac output during resuscitation . In each group 60 patients with out-of-hospital cardiac arrest were treated either with the st and ard or the ACD method . End-tidal CO2 ( p(et)CO2 , mmHg ) was assessed with a side-stream capnometer following intubation and then every 2 min up to 10 min or restoration of spontaneous circulation ( ROSC ) . There was no difference in p(et)CO2 between both patient groups . However , CO2 was significantly higher in patients who were admitted to hospital as compared to patients declared dead at the scene . All of the admitted patients had a p(et)CO2 of at least 15 mmHg no later than 2 min following intubation , none of the dead patients ever exceeded 15.5 mmHg . From these data we conclude that capnometry adds valuable information to the estimation of a patient 's prognosis in the field ( threshold , 15 mmHg ) , but we could not detect any difference in p(et)CO2 between ACD and st and ard CPR Objective : Generation of negative intrathoracic pressure during the decompression phase of cardiopulmonary resuscitation enhances the refilling of the heart . We tested the hypothesis that when compared with closed-chest manual compressions at 80 chest compressions per min , treatment with active compression-decompression cardiopulmonary resuscitation at 80 chest compressions/min combined with augmentation of negative intrathoracic pressure would lower intracranial pressure and increase cerebral perfusion , thereby improving neurologically intact survival rates following prolonged untreated cardiac arrest . Design : Prospect i ve , r and omized animal study . Setting : Animal laboratory facilities . Subjects : A total of 26 female farm pigs in two different protocol s ( n = 17 and n = 9 ) . Interventions , Measurements , and Main Results : Seventeen pigs were subjected to 8.5 mins of untreated ventricular fibrillation and prospect ively r and omized to cardiopulmonary resuscitation at 80 chest compressions/min or active compression-decompression cardiopulmonary resuscitation at 80 chest compressions/min plus an impedance threshold device . Coronary perfusion pressures ( 29.5 ± 2.7 mm Hg vs. 22.4 ± 1.6 mm Hg , p = .03 ) , carotid blood flow ( 44.0 ± 12.2 vs. 30.9 ± 10.4 , p = .03 ) , and 24-hr neurological survival ( 88 % vs. 22 % , p = .015 ) were higher with active compression-decompression cardiopulmonary resuscitation + an impedance threshold device . Cerebral perfusion pressures , measured in nine additional pigs , were improved with active compression-decompression cardiopulmonary resuscitation + an impedance threshold device ( 21.9 ± 1.2 mm Hg vs. 8.9 ± 0.8 mm Hg , p < .0001 ) . With active compression-decompression cardiopulmonary resuscitation + impedance threshold device , mean diastolic intracranial pressure during decompression was lower ( 12.2 ± 0.2 mm Hg vs. 16.6 ± 1.2 mm Hg , p = .02 ) and the downward slope of the decompression phase intracranial pressure curve was steeper ( −60.3 ± 12.9 mm Hg vs. −46.7 ± 11.1 mm Hg/sec , p < .001 ) . Conclusions : Active compression-decompression cardiopulmonary resuscitation + an impedance threshold device increased cerebral perfusion pressures and lowered diastolic intracranial pressure and intracranial pressure rate during the decompression phase . These mechanisms may underlie the observed increase in cerebral perfusion pressure , carotid blood flow , and survival rates with favorable neurologic outcomes in this pig model of cardiac arrest |
2,252 | 25,213,734 | Experimental studies have shown that the virus can be transferred from contaminated h and s to food and surfaces . | 908 www.thelancet.com/infection Vol 14 October 2014 Despite the necessary and major goal of containment of artemisinin resistance in Plasmodium falciparum , not all malaria is caused by P falciparum and outside of Africa the greatest malaria burden is attributable to Plasmodium vivax .
They conclude that chloroquine-resistant P vivax is now present across most of vivax-endemic regions .
post-exposure prophylaxis to more than 10 000 people .
In Europe , active vaccination against hepatitis A is currently recommended mainly for travelers visiting countries endemic for hepatitis A virus .
International travel is a risk factor , accounting for about a third of cases in Austria and Germany .
By contrast with Germany , the Austrian national vaccination plan since 2008 has included a recommendation of hepatitis A virus vaccination for all seronegative food h and lers in food production and gastronomy companies .
Viral contamination of food can occur anywhere in the production process , but most foodborne viral infections can be traced back to infected people who h and led food that is not heated or otherwise treated afterwards . | BACKGROUND Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease . There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border , historically a site of emerging antimalarial-drug resistance . METHODS In two open-label , r and omized trials , we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin , western Cambodia , and Wang Pha , northwestern Thail and : oral artesunate given at a dose of 2 mg per kilogram of body weight per day , for 7 days , and artesunate given at a dose of 4 mg per kilogram per day , for 3 days , followed by mefloquine at two doses totaling 25 mg per kilogram . We assessed in vitro and in vivo Plasmodium falciparum susceptibility , artesunate pharmacokinetics , and molecular markers of resistance . RESULTS We studied 40 patients in each of the two locations . The overall median parasite clearance times were 84 hours ( interquartile range , 60 to 96 ) in Pailin and 48 hours ( interquartile range , 36 to 66 ) in Wang Pha ( P<0.001 ) . Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients ( 30 % ) receiving artesunate monotherapy and 1 of 20 ( 5 % ) receiving artesunate-mefloquine therapy in Pailin , as compared with 2 of 20 ( 10 % ) and 1 of 20 ( 5 % ) , respectively , in Wang Pha ( P=0.31 ) . These markedly different parasitologic responses were not explained by differences in age , artesunate or dihydroartemisinin pharmacokinetics , results of isotopic in vitro sensitivity tests , or putative molecular correlates of P. falciparum drug resistance ( mutations or amplifications of the gene encoding a multidrug resistance protein [ PfMDR1 ] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [ PfSERCA ] ) . Adverse events were mild and did not differ significantly between the two treatment groups . CONCLUSIONS P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thail and . Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing . Containment measures are urgently needed . ( Clinical Trials.gov number , NCT00493363 , and Current Controlled Trials number , IS RCT N64835265 . |
2,253 | 15,965,032 | Of the seven models , that of CHW pneumonia case management ( Model 6 ) has the strongest evidence for an impact on mortality . | A systematic review was conducted to categorize and describe Intervention Models involving community health workers ( CHWs ) that aim to improve case management of sick children at the household and community levels . | The contribution of acute respiratory infection control project within the framework of micro-credit-based development intervention in promoting maternal knowledge of ARIs in children was assessed . Data came from a cross-sectional survey of 2814 mothers of under 5-y-old children residing in 200 r and omly selected villages in five districts in Bangladesh . Findings revealed that the ARI control project had significant positive effects in raising knowledge of clinical signs and preventive measures . When ARI control project activities were integrated with the credit-based development initiative , maternal knowledge improved even further . The study concludes that the micro-credit programme can be a catalytic agent in raising health knowledge among poor women in developing countries BACKGROUND The Integrated Management of Childhood Illness ( IMCI ) strategy is design ed to address major causes of child mortality at the levels of community , health facility , and health system . We assessed the effectiveness of facility-based IMCI in rural Tanzania . METHODS We compared two districts with facility-based IMCI and two neighbouring comparison districts without IMCI , from 1997 to 2002 , in a non-r and omised study . We assessed quality of case-management for children 's illness , drug and vaccine availability , and supervision involving case-management , through a health-facility survey in 2000 . Household surveys were used to assess child-health indicators in 1999 and 2002 . Survival of children was tracked through demographic surveillance over a predefined 2-year period from mid 2000 . Further information on context ual factors was gathered through interviews and record review . The economic cost of health care for children in IMCI and comparison districts was estimated through interviews and record review at national , district , facility , and household levels . FINDINGS During the IMCI phase-in period , mortality rates in children under 5 years old were almost identical in IMCI and comparison districts . Over the next 2 years , the mortality rate was 13 % lower in IMCI than in comparison districts ( 95 % CI -7 to 30 or 5 to 21 , depending on how adjustment is made for district-level clustering ) , with a rate difference of 3.8 fewer deaths per 1000 child-years . Context ual factors , such as use of mosquito nets , all favoured the comparison districts . Costs of children 's health care with IMCI were similar to or lower than those for case-management without IMCI . INTERPRETATION Our findings indicate that facility-based IMCI is good value for money , and support widespread implementation in the context of health-sector reform , basket funding , good facility access , and high utilisation of health facilities OBJECTIVES To characterize community health worker ( CHW ) performance using an algorithm for managing common childhood illnesses in Siaya District , Kenya , we conducted CHW evaluations in 1998 , 1999 , and 2001 . METHODS R and omly selected CHWs were observed managing sick outpatient and inpatient children at a hospital , and their management was compared with that of an expert clinician who used the algorithm . RESULTS One hundred , 108 , and 114 CHWs participated in the evaluations in 1998 , 1999 , and 2001 , respectively . The proportions of children treated " adequately " ( with an antibiotic , antimalarial , oral rehydration solution , or referral , depending on the child 's disease classifications ) were 57.8 % , 35.5 % , and 38.9 % , respectively , for children with a severe classification and 27.7 % , 77.3 % , and 74.3 % , respectively , for children with a moderate ( but not severe ) classification . CHWs adequately treated 90.5 % of malaria cases ( the most commonly encountered classification ) . CHWs often made mistakes assessing symptoms , classifying illnesses , and prescribing correct doses of medications . CONCLUSIONS Deficiencies were found in the management of sick children by CHWs , although care was not consistently poor . Key reasons for the deficiencies appear to be guideline complexity and inadequate clinical supervision ; other possible causes are discussed OBJECTIVE The objective of this study was to assess the effect of Integrated Management of Childhood Illness ( IMCI ) case management training on the use of antimicrobial drugs among health-care workers treating young children at first-level facilities . Antimicrobial drugs are an essential child-survival intervention . Ensuring that children younger than five who need these drugs receive them promptly and correctly can save their lives . Prescribing these drugs only when necessary and ensuring that those who receive them complete the full course can slow the development of antimicrobial resistance . METHODS Data collected through observation-based surveys in r and omly selected first-level health facilities in Brazil , Ug and a and the United Republic of Tanzania were statistically analysed . The surveys were carried out as part of the multi-country evaluation of IMCI effectiveness , cost and impact ( MCE ) . FINDINGS Results from three MCE sites show that children receiving care from health workers trained in IMCI are significantly more likely to receive correct prescriptions for antimicrobial drugs than those receiving care from workers not trained in IMCI . They are also more likely to receive the first dose of the drug before leaving the health facility , to have their caregiver advised how to administer the drug , and to have caregivers who are able to describe correctly how to give the drug at home as they leave the health facility . CONCLUSIONS IMCI case management training is an effective intervention to improve the rational use of antimicrobial drugs for sick children visiting first-level health facilities in low-income and middle-income countries BACKGROUND No satisfactory strategy for reducing high child mortality from malaria has yet been established in tropical Africa . We compared the effect on under-5 mortality of teaching mothers to promptly provide antimalarials to their sick children at home , with the present community health worker approach . METHODS Of 37 tabias ( cluster of villages ) in two districts with hyperendemic to holoendemic malaria , tabias reported to have the highest malaria morbidity were selected . A census was done which included a maternity history to determine under-5 mortality . Tabias ( population 70,506 ) were paired according to under-5 mortality rates . One tabia from each pair was allocated by r and om number to an intervention group and the other was allocated to the control group . In the intervention tabias , mother coordinators were trained to teach other local mothers to recognise symptoms of malaria in their children and to promptly give chloroquine . In both intervention and control tabias , all births and deaths of under-5s were recorded monthly . FINDINGS From January to December 1997 , 190 of 6383 ( 29.8 per 1000 ) children under-5 died in the intervention tabias compared with 366 of 7294 ( 50.2 per 1000 ) in the control tabias . Under-5 mortality was reduced by 40 % in the intervention localities ( 95 % CI from 29.2 - 50.6 ; paired t test , p<0.003 ) . For every third child who died , a structured verbal autopsy was undertaken to ascribe cause of mortality as consistent with malaria or possible malaria , or not consistent with malaria . Of the 190 verbal autopsies , 13 ( 19 % ) of 70 in the intervention tabias were consistent with possible malaria compared with 68 ( 57 % ) of 120 in the control tabias . INTERPRETATION A major reduction in under-5 mortality can be achieved in holoendemic malaria areas through training local mother coordinators to teach mothers to give under-5 children antimalarial drugs A survey was done in June 1983 in Saradidi , Kenya , one year after the inception of a community-based malaria control programme to determine if people were obtaining malaria treatment from volunteer village health helpers ( VHH 's ) chosen by the community . Ten of 36 villages were r and omly chosen . From these ten villages , 100 households were r and omly selected and 222 people ten years of age or more were interviewed ; 113 ( 50.9 % ) had a history of malaria in the previous two weeks and 82 ( 72.6 % of 113 ) had taken medicine for malaria in that period . Of these 82 , 51.2 % obtained drug from the VHH , 28 % purchased it from a shop , 12.2 % from a health facility , 4.9 % from family members and 3.7 % from a private practitioner or a shop outside Saradidi . Reasons given for not obtaining treatment from the VHH 's among the 40 people who went elsewhere for treatment included : the VHH was not at home when needed ( 35 % ) ; the VHH had no drugs ( 22.5 % ) ; the patient was too sick for the VHH to treat ( 10 % ) ; had drugs already in the home ( 10 % ) ; ' not registered ' with VHH ( 10 % ) ; VHH ' no good ' ( 7.5 % ) ; and more ' convenient ' to go elsewhere ( 5 % ) . Similar results found on question ing the mother were obtained for 103 children under nine years old in these households ; 67 ( 65.0 % ) children had a history of malaria in the previous two weeks and 59 ( 88.1 % ) of these 67 children had received antimalarial treatment . The VHH was the principal source of treatment ( 50.8 % of 59 ) , followed by health facilities ( 20.3 % ) and shops ( 18.6 % ) . ( ABSTRACT TRUNCATED AT 250 WORDS Save the Children/USA in collaboration with the Ministry of Health of Mali has established over 300 village drug kits in southern Mali since 1996 . A cluster-r and omized trial was conducted between November 2001 and February 2002 in 10 health zones of Bougouni District to evaluate an intervention to ( i ) improve the skills of the village drug kit managers to counsel parents on correct home administration of chloroquine ( CQ ) , and ( ii ) increase the referral of sick children to community health centres ( CHC ) . Children 's carers were interviewed 5 d after the sale of CQ about knowledge of danger signs requiring referral , quality of counselling , administration of CQ , and referral . The intervention was associated with significant increases in knowledge of danger signs requiring referral , reported quality of counselling by the manger of the drug kit , and correct administration of CQ in the home . Parents reported that 42.1 % of children in the intervention group were referred to the CHC by the drug kit manager compared with 11.2 % in the comparison group ( odds ratio = 7.12 , 95 % CI 2.62 - 19.38 ) . CHC registers indicated that 87.0 % of referrals recorded in drug kit referral notebooks arrived at the health centre . Further research is needed to increase the effectiveness of the counselling and the community referral mechanism tested in this study In rural , malaria-endemic Burkina Faso , we evaluated the impact of the use of pre-packaged antimalarial drugs ( PPAM ) , by mothers in the home , on the progression of disease in children from uncomplicated fever to severe malaria . In each village of one province , a core group of opinion leaders ( mainly older mothers ) was trained in the management of uncomplicated malaria , including the administration of PPAM . Full courses of antimalarial ( chloroquine ) and antipyretic ( aspirin ) drugs were packaged in age-specific bags and made widely available through community health workers who were supplied through the existing drug distribution system . Drugs were sold under a cost-recovery scheme . Local schoolteachers conducted surveys in a r and om sample of 32 villages at the end of the high transmission seasons in 1998 and 1999 . Disease history and the treatment received were investigated for all children under the age of 6 years having suffered from a fever episode in the previous 4 weeks . ' Uncomplicated malaria ' was defined as every episode of fever and ' severe malaria ' as every episode of fever followed by convulsions or loss of consciousness . During the study period , 56%[95 % confidence interval ( CI ) 50 - 62 % ] of 3202 fever episodes in children under 6 years of age were treated promptly by mothers with the pre-packaged drugs made available by the study . A total of 59 % of children receiving PPAM were reported to have received the drugs over the prescribed 3-day period , while 52 % received the correct age-specific dose . PPAM use was similar among literate ( 61 % ) and non-literate mothers ( 55 % ) ( P = 0.08 ) . The overall reported risk of developing severe malaria was 8 % . This risk was lower in children treated with PPAM ( 5 % ) than in children not treated with PPAM ( 11 % ) ( risk ratio = 0.47 ; 95 % CI 0.37 , 0.60 ; P < 0.0001 ) . This estimate of the impact of PPAM was largely unchanged when account was taken of potential confounding by age , sex , maternal literacy status , year or village . Our findings support the view that , after appropriate training and with adequately packaged drugs made available , mothers can recognize and treat promptly and correctly malarial episodes in their children and , by doing so , reduce the incidence of severe disease BACKGROUND We report the preliminary findings from a continuing cluster r and omised evaluation of the Integrated Management of Childhood Illness ( IMCI ) strategy in Bangladesh . METHODS 20 first-level outpatient facilities in the Matlab sub-district and their catchment areas were r and omised to either IMCI or st and ard care . Surveys were done in households and in health facilities at baseline and were repeated about 2 years after implementation . Data on use of health facilities were recorded . IMCI implementation included health worker training , health systems support , and community level activities guided by formative research . FINDINGS 94 % of health workers in the intervention facilities were trained in IMCI . Health systems supports were generally available , but implementation of the community activities was slow . The mean index of correct treatment for sick children was 54 in IMCI facilities compared with 9 in comparison facilities ( range 0 - 100 ) . Use of the IMCI facilities increased from 0.6 visits per child per year at baseline to 1.9 visits per child per year about 21 months after IMCI introduction . 19 % of sick children in the IMCI area were taken to a health worker compared with 9 % in the non-IMCI area . INTERPRETATION 2 years into the assessment , the results show improvements in the quality of care in health facilities , increases in use of facilities , and gains in the proportion of sick children taken to an appropriate health care provider . These findings are being used to strengthen child health care nationwide . They suggest that low levels of use of health facilities could be improved by investing in quality of care and health systems support Mortality and fertility rates were measured from 1981 to 1983 by prospect i ve registration of vital events as part of a community-based malaria control and health development programme in Saradidi , Kenya . There was no obvious effect of providing chloroquine phosphate for treatment of malaria in each village on mortality or fertility rates . Crude death rates were 13.1 in the year before intervention ( 1 May 1981 to 30 April 1982 ) and 12.3 after intervention ( 1 September 1982 to 31 August 1983 ) . Neonatal mortality increased from 36.8 per 1000 live births pre-intervention to 49.1 during intervention . There was a slight decline in post-neonatal ( one to 12 months ) mortality ( 72.8 to 67.0 ) and a significant drop in early childhood mortality ( 25.2 to 18.2 ) . The change in mortality rates in these two age groups were fully explained by a high rate of measles mortality in the pre-intervention period . Measles accounted for 35.7 % of 284 reported deaths in infants one to 12 months of age and for 40.9 % of 230 deaths in children one to four years old . There was little change in reported malaria-specific mortality rates in infants and young children most likely because of a high level of chloroquine use for treatment of presumptive illness . Perinatal mortality by area ranged between 60.4 and 81.3 pre-intervention to 79.5 to 97.2 after the control programme was instituted . Crude birth rates by area remained stable at about 40 and general fertility rates were about 200 . Both pre-intervention and during intervention infants were significantly more likely to have died without medical consultation than children one to four years . However , 79.2 % of 284 infants and 90.7 % of 193 children died in spite of having consulted a health worker prior to death . The data suggest that a measles vaccine programme would significantly reduce mortality rates in infants and young children . The fact that the majority of infants and young children died in spite of receiving medical attention indicates both the inadequacy of curative medical services in this high mortality setting as well as the necessity for promoting preventive health measures A prospect i ve study was conducted to determine the magnitude of morbidity and mortality caused by acute respiratory infections ( ARI ) among children under 5 years of age and to assess the feasibility of reducing mortality owing to ARI by the use of community health workers . Villages selected for this study were situated on the south-west edge of Kathm and u Valley , about 24 km from the city centre . The study group consisted of 1019 children under the age of 5 years at the beginning of the study and followed for 3 years . During the 1st year , baseline information was collected . During the 2nd and 3rd years , intervention measures ( health education , immunization and antibiotics for children with signs suggesting pneumonia ) were taken and their effect assessed . There was a 59 % reduction in the ARI-specific death rate among study children between surveillance year and intervention year I and a further 25 % reduction in the ARI-specific death rate between intervention years I and II . Despite a substantial reduction in ARI mortality with the interventions , there was still an unacceptably high mortality from chronic diarrhoea , malnutrition and other factors . This implies that the programme to control ARI , diarrhoea , malnutrition and immunizable diseases should be integrated into one , within the framework of a primary health care strategy Integrated Management of Childhood Illness ( IMCI ) has been adopted by over 80 countries as a strategy for reducing child mortality and improving child health and development . It includes complementary interventions design ed to address the major causes of child mortality at community , health facility , and health system levels . The Multi-Country Evaluation of IMCI Effectiveness , Cost and Impact ( IMCI-MCE ) is a global evaluation to determine the impact of IMCI on health outcomes and its cost-effectiveness . The MCE is coordinated by the Department of Child and Adolescent Health and Development of the World Health Organization . MCE studies are under way in Bangladesh , Brazil , Peru , Tanzania and Ug and a. In Tanzania , the IMCI-MCE study uses a non-r and omized observational design comparing four neighbouring districts , two of which have been implementing IMCI in conjunction with evidence -based planning and expenditure mapping at district level since 1997 , and two of which began IMCI implementation in 2002 . In these four districts , child health and child survival are documented at household level through cross-sectional , before- and -after surveys and through longitudinal demographic surveillance respectively . Here we present results of a survey conducted in August 2000 in stratified r and om sample s of government health facilities to compare the quality of case-management and health systems support in IMCI and comparison districts . The results indicate that children in IMCI districts received better care than children in comparison districts : their health problems were more thoroughly assessed , they were more likely to be diagnosed and treated correctly as determined through a gold-st and ard re-examination , and the caretakers of the children were more likely to receive appropriate counselling and reported higher levels of knowledge about how to care for their sick children . There were few differences between IMCI and comparison districts in the level of health system support for child health services at facility level . This study suggests that IMCI , in the presence of a de central ized health system with practical health system planning tools , is feasible for implementation in re source -poor countries and can lead to rapid gains in the quality of case-management . IMCI is therefore likely to lead to rapid gains in child survival , health and development if adequate coverage levels can be achieved and maintained In a community-based intervention trial to reduce childhood mortality from pneumonia the intervention area included 58 villages ( 6176 children aged 0 - 4 years ) and the control area 44 villages ( 3947 children ) in Gadchiroli , India . The interventions included mass education about childhood pneumonia and case-management of pneumonia by paramedics , village health workers , and traditional birth attendants ( TBAs ) who were trained to recognise childhood pneumonia and treat it with co-trimoxazole . Parents sought treatment , and coverage was 76 % without active case-detection efforts . The case-fatality rate among the 612 cases treated by health workers was 0.8 % , compared with 13.5 % in the control area . After a year of intervention pneumonia-specific childhood mortality was significantly lower in the intervention than in the control area ( 8.1 vs 17.5 deaths per 1000 children under 5 years ) ; the difference between the areas was greatest in children under 1 year . The differences in infant mortality ( 89 vs 121 per 1000 ) and total under-5 mortality ( 28.5 vs 40.7 per 1000 ) were highly significant . Mortality from other causes remained similar in the two areas but neonatal mortality due to birth injury and prematurity was significantly lower in the intervention area , presumably owing to the combination of better maternal and neonatal care by the TBAs trained in the project and the availability of treatment for pneumonia . The cost of co-trimoxazole was US $ 0.025 per child per year ( $ 2.64 per child saved ) Two drug strategies for the control of malaria in children aged 3 - 59 months have been compared in a rural area of The Gambia -- treatment of presumptive episodes of clinical malaria with chloroquine by village health workers , and treatment combined with fortnightly chemoprophylaxis with ' Maloprim ' ( pyrimethamine/dapsone ) which was also given by village health workers . Treatment alone did not have any significant effect on mortality or morbidity from malaria . In contrast , treatment and chemoprophylaxis reduced overall mortality in children aged 1 - 4 years , mortality from probable malaria , and episodes of fever associated with malaria parasitaemia . A high level of compliance with chemoprophylaxis was obtained and no harmful consequences of chemoprophylaxis were observed |
2,254 | 18,254,056 | The primary outcome measure was tooth loss , secondary outcomes were reduction of probing depth , bleeding on probing and gain in probing attachment .
All treatment modalities led to significant improvements in clinical parameters after a follow up of at least 3 months .
No significant differences were observed for any of the outcome measures , when comparing FMS and control .
AUTHORS ' CONCLUSIONS In patients with chronic periodontitis in moderately deep pockets slightly more favourable outcomes for pocket reduction and gain in probing attachment were found following FMD compared to control .
However , these additional improvements were only modest and there was only a very limited number of studies available for comparison , thus limiting general conclusions about the clinical benefit of full-mouth disinfection | BACKGROUND In an attempt to enhance treatment outcomes , alternative protocol s for anti-infective periodontal therapy have been introduced .
OBJECTIVES To evaluate the effectiveness of full-mouth disinfection or full-mouth scaling compared to conventional quadrant scaling for periodontitis . | A classical treatment for chronic adult periodontitis consists of four to six consecutive sessions of scaling and root planing at a 1- to 2-week interval . Such a so-called " quadrant or sextant therapy " might result in a reinfection of a previously disinfected area by bacteria from an untreated region . The purpose of this study was to investigate , over an 8-month period , the clinical benefits of full-mouth disinfection within a 24-hour period in the control of chronic periodontitis . Ten adult patients with advanced chronic periodontitis were r and omly assigned to a test and a control group . The control group received the st and ard scheme of initial periodontal therapy , consisting of scaling and root planing of the four quadrants was performed within 24 hours and immediately followed by a thorough supra- and subgingival chlorhexidine application to limit any transfer of bacteria . The latter involved tongue brushing with a 1 % chlorhexidine gel for 60 seconds , mouthrinsing with a 0.2 % chlorhexidine solution twice for 60 seconds , repeated subgingival irrigation of all pockets with a 1 % chlorhexidine gel ( 3 times within 10 minutes ) , and mouthrinsing twice daily with a 0.2 % chlorhexidine solution during 2 weeks . In addition , both groups received thorough oral hygiene instructions . The plaque index , gingival index , probing depth , gingival recession , and bleeding on probing were recorded prior to professional cleaning and at 1 , 2 , 4 , and 8 months afterwards . Although the test group scored higher plaque indices than the control group , especially at months 2 and 4 , the gingival index and bleeding tendency showed similar improvements with time . However , when the gingival/plaque ratio was considered , the latter was lower in the test group at all follow-up visits . For pockets > or = 7 mm , full-mouth disinfection showed a significantly ( P = 0.01 ) higher reduction in probing depth at each follow-up visit with , at month 8 , a reduction of 4 mm ( from 8 mm to 4 mm ) , in comparison to 3 mm ( from 8 mm to 5 mm ) for the classical therapy . The increase in gingival recession in the full-mouth disinfection group remained below 0.7 mm , while in the control group it reached 1.9 mm after 8 months . This result ed in a gain of clinical attachment level of 3.7 mm for the test group versus 1.9 mm for the control group . A radiographical examination also indicated a superior improvement for the test group when compared to the control group . This pilot study suggests that a full-mouth disinfection in one day results in an improved clinical outcome in chronic periodontitis as compared to scalings per quadrant at 2-week intervals over several weeks A treatment for periodontal infections often consists of consecutive rootplanings ( per quadrant , at a 1- to 2-week interval ) , without a proper disinfection of the remaining intra-oral niches ( untreated pockets , tongue , saliva , mucosa and tonsils ) . Such an approach , could theoretically lead to a reinfection of previously-treated pockets . The present study aims to examine the effect of a full-mouth disinfection on the microbiota in the above-mentioned niches . Moreover , the clinical benefit of such an approach was investigated . 16 patients with severe periodontitis were r and omly allocated to a test and a control group . The patients from the control group were scaled and rootplaned , per quadrant , at 2-week intervals and obtained oral hygiene instructions . The patients from the test group received a full-mouth disinfection consisting of : scaling and rootplaning of all pockets in 2 visits within 24 h , in combination with tongue brushing with 1 % chlorhexidine gel for 1 min , mouth rinsing with a 0.2 % chlorhexidine solution for 2 min and subgingival irrigation of all pockets ( 3x in 10 min ) with 1 % chlorhexidine gel . Besides oral hygiene , the test group rinsed 2x daily with 0.2 % chlorhexidine and sprayed the tonsils with a 0.2 % chlorhexidine for 2 months . Plaque sample s ( pockets , tongue , mucosa and saliva ) were taken at baseline and after 2 and 4 months , and changes in probing depth , attachment level and bleeding on probing were reported . The full-mouth disinfection result ed in a statistically significant additional reduction/elimination of periodontopathogens , especially in the subgingival pockets , but also in the other niches . These microbiological improvements were reflected in a statistically-significant higher probing depth reduction and attachment gain in the test patients . These findings suggest that a disinfection of all intra-oral niches within a short time span leads to significant clinical and microbiological improvements for up to 4 months OBJECTIVES The beneficial effects of the one-stage , full-mouth disinfection remain controversial in the scientific literature . This might be due to the fact that an entire mouth disinfection with the use of antiseptics has been confused with a full-mouth scaling and root planing . This parallel , single blind RCT study aim ed to compare several full-mouth treatment strategies with each other . MATERIAL AND METHODS Seventy-one patients with moderate periodontitis were r and omly allocated to one of the following treatment strategies : scaling and root planing , quadrant by quadrant , at two-week intervals ( negative control , NC ) , full-mouth scaling and root planing within 2 consecutive days ( FRP ) , or three one-stage , full-mouth disinfection ( FM ) protocol s within 2 consecutive days applying antiseptics to all intra-oral niches for periopathogens using as antiseptics : chlorhexidine ( FMCHX ) for 2 months , amine fluoride/stannous fluoride for 2 months ( FMF ) , or chlorhexidine for 2 months followed by amine fluoride/stannous fluoride for another 6 months ( FMCHX+F ) . At baseline and after 2 , 4 , and 8 a series of periodontal parameters were recorded . RESULTS All treatment strategies result ed in significant ( p<0.05 ) improvements of all clinical parameters over the entire duration of the study . Inter-treatment differences were often encountered . The NC group nearly always showed significant smaller improvements than the two CHX groups . The differences between the FRP or FM groups , and the two CHX groups only sporadically reached a statistical significance . CONCLUSION These observations indicate that the benefits of the " OSFMD " protocol are partially due to the use of the antiseptics and partially to the completion of the therapy in a short time BACKGROUND / AIMS Recent studies reported significant additional clinical and microbiological improvements when severe adult periodontitis was treated by means of a " one-stage full-mouth " disinfection instead of a st and ard treatment strategy with consecutive root planings quadrant per quadrant . The one stage full-mouth disinfection procedure involves scaling and root planing of all pockets within 24 h in combination with an extensive application of chlorhexidine to all intra-oral niches such as periodontal pockets , tongue dorsum , tonsils ( chairside , and at home for 2 months ) . This study aims to examine the relative importance of the use of chlorhexidine in the one stage full-mouth disinfection protocol . METHODS Therefore , 3 groups of 12 patients each with advanced periodontitis were followed , both from a clinical and microbiological point of view , over a period of 8 months . The patients from the control group were scaled and root planed , quadrant per quadrant . at two-week intervals . The 2 other groups underwent a one stage full-mouth scaling and root planing ( all pockets within 24 h ) with ( Fdis ) or without ( FRp = full-mouth root planing ) the adjunctive use of chlorhexidine . At baseline and after 1 , 2 , 4 and 8 months , the following clinical parameters were recorded : plaque and gingivitis indices , probing depth , bleeding on probing and clinical attachment level . Microbiological sample s were taken from different intra-oral niches ( tongue , mucosa , saliva and pooled sample s from single- and multi-rooted teeth ) . The sample s were cultured on selective and non-selective media in order to evaluate the number of CFU/ml for the key-periodontopathogens . At baseline , an anonymous question naire was given to the patients to record the perception of each treatment ( post operative pain , fever , swelling etc . ) . RESULTS All 3 treatment strategies result ed in significant improvements for all clinical parameters , but the Fdis and FRp patients reacted always significantly more favourably than the control group , with an additional probing depth reduction of + /- 1.5 mm and an additional gain in attachment of + /- 2 mm ( for pockets > or = 7 mm ) . Also from a microbiological point of view both the FRp and Fdis patients showed additional improvements when compared to the control group , as well in the reduction of spirochetes and motile organisms as in the number of CFU/ml of the key-pathogens , especially when the subgingival plaque sample s were considered . The differences between FRp and Fdis patients were negligible . CONCLUSIONS These findings suggest that the benefits of a " one-stage full-mouth disinfection " in the treatment of patients suffering from severe adult periodontitis probably results from the full-mouth scaling and root planing within 24 h rather than the beneficial effect of chlorhexidine . The raise in body temperature the second day after the full-mouth scaling and root planing seems to indicate a Shwartzman reaction BACKGROUND The aim of the present study was to evaluate the effectiveness of non-surgical mechanical instrumentation at 2 different time intervals on short-term healing and to assess patient reactions following non-surgical periodontal therapy . METHODS The study population consisted of 100 patients with moderate periodontal disease . Patients were equally distributed into 2 groups , treated daily or weekly . The daily group received full-mouth daily scaling and root planing for 4 consecutive days . The weekly group was treated once a week for 4 weeks . All patients were asked for objective ( lymphadenopathy , aphthous stomatitis , and edema ) and subjective ( fatigue , pain , pruritus , burning sensation , and dentinalgia ) reactions . Clinical measurements of plaque index ( PI ) , gingival index ( GI ) , probing depth ( PD ) , bleeding on probing ( BOP ) , and gingival recession ( GR ) were taken at baseline and 3 months after treatment . All of the objective and subjective reactions were recorded after each treatment session . RESULTS The results of our study revealed a significant decrease in PI , GI , BOP , and PD measurements at the end of the third month , but no significant changes in GR . The incidence of subjective and objective reactions was higher in the daily treated group compared to those in the weekly group . Most of these complaints were observed after the third treatment session . CONCLUSIONS Within the limits of this study , no differences were observed between the study groups when the clinical parameters were evaluated . However , taking the subjective and objective reactions into consideration , the smallest time interval for non-surgical periodontal procedures might be 1 week BACKGROUND The aim of the present study was to evaluate the clinical effects of one-stage periodontal debridement with an ultrasonic instrument , associated with 0.5 % povidone (pvp)-iodine irrigation in patients with chronic periodontitis . METHODS Forty-five patients were r and omly assigned into three groups : the control group ( CG ) received quadrant root planing at 1-week intervals over four consecutive sessions ; the periodontal debridement plus pvp-iodine group ( PD-PIG ) received a 45-minute full-mouth debridement with an ultrasonic instrument , associated with 0.5 % pvp-iodine irrigation ; and the periodontal debridement group ( PDG ) received a 45-minute full-mouth periodontal debridement with an ultrasonic instrument , associated with NaCl irrigation . RESULTS At the 3-month evaluation , the mean probing depth ( PD ) reduction in CG was 2.51+/-0.52 mm , 2.53+/-0.50 mm in PD-PIG , and 2.58+/-0.60 mm in PDG ( P<0.05 ) . The clinical attachment level ( CAL ) analysis showed a statistically significant gain in all groups compared to baseline ( 1.87+/-0.56 mm [ CG ] , 1.94+/-0.70 mm [ PD-PIG ] , and 1.99+/-0.92 mm [ PDG ] ) . Intergroup analysis of PD and CAL at 1 and 3 months showed no differences ( P>0.05 ) . The N-benzoyl-L-arginine-p-nitroanilide ( BAPNA ) test showed a significant reduction in trypsin activity only during the first month ( P<0.05 ) ; at 3 months there were no differences compared to baseline ( P=0.80 ) . CONCLUSION This study provides no evidence that pvp-iodine is effective as an adjunct for one-stage periodontal debridement In a st and ard periodontal treatment strategy with consecutive root planings ( per quadrant at a one- to two-week interval ) , re-infection of a disinfected area might occur before completion of the treatment . This study examines , both clinical ly and microbiologically , whether a full-mouth disinfection within 24 hours significantly improves the outcome of periodontal treatment . Ten patients with advanced chronic periodontitis were r and omly allocated to a test and a control group . The patients from the control group received scalings and root planings as well as oral hygiene instructions per quadrant at two-week intervals . Full-mouth disinfection in the test group was sought by the removal of all plaque and calculus ( in two visits within 24 hours ) . In addition , at each of these visits , the tongue was brushed with a 1 % chlorhexidine gel for one min and the mouth rinsed with a 0.2 % chlorhexidine solution for two min . Furthermore , subgingival chlorhexidine ( 1 % ) irrigation was performed in all pockets . The recolonization of the pockets was retarded by oral hygiene and 0.2 % chlorhexidine rinses during two weeks . The clinical parameters were recorded , and plaque sample s were taken from the right upper quadrant at baseline and after one and two months . The test group patients showed a significantly higher reduction in probing depth for deep pockets at both follow-up visits ( p < 0.05 ) . At the one-month visit , differential phase-contrast microscopy revealed significantly lower proportions of spirochetes and motile rods in the test group ( p = 0.01 ) . Culturing showed that the test group harbored significantly fewer pathogenic organisms at one month ( p = 0.005 ) . At two months , the same sites harbored singificantly more " beneficial " bacteria ( p = 0.02 ) . Moreover , all sites of the test group initially harboring P. gingivalis ( 6/10 ) became negative after treatment . These findings suggest that it is possible to achieve a significant improvement of the treatment outcome ( both microbiologically and clinical ly ) with a one-stage full-mouth disinfection BACKGROUND The aim of this r and omized controlled clinical trial was to determine the effects of single-visit full-mouth ultrasonic debridement versus quadrant-wise therapy . MATERIAL AND METHODS Thirty-six subjects with chronic periodontitis , were r and omly allocated to three groups -- quadrant-wise ultrasonic debridement , single-visit full-mouth ultrasonic debridement with povidone iodine and single-visit full-mouth ultrasonic debridement with water . Whole-mouth plaque , bleeding on probing ( BOP ) , pocket depth and attachment level were recorded before treatment and 1 , 3 and 6 months post-treatment . Plaque and saliva sample s were collected for microbiological analysis . RESULTS After treatment , all groups showed significant improvement in clinical parameters . Full-mouth treatments result ed in similar improvements in full-mouth mean plaque percentage , probing pocket depth and probing attachment level as conventional therapy . When data were analysed based on pocket depth and tooth type , there was no difference between groups in probing depth reduction or attachment gains . The full-mouth groups demonstrated greater reduction in BOP% and number of pockets > or = 5 mm and the total treatment time was significantly shorter . The detection frequencies of periodontal pathogens in plaque and saliva showed slight changes with no difference between groups . CONCLUSION Single-visit full-mouth mechanical debridement may have limited additional benefits over quadrant-wise therapy in the treatment of periodontitis , but can be completed in a shorter time AIM To evaluate the clinical efficacy of ( i ) a single session of " full-mouth ultrasonic debridement " ( Fm-UD ) as an initial periodontal treatment approach and ( ii ) re-instrumentation of periodontal pockets not properly responding to initial subgingival instrumentation . METHODS Forty-one patients , having on the average 35 periodontal sites with probing pocket depth ( PPD ) > or = 5 mm , were r and omly assigned to two different treatment protocol s following stratification for smoking : a single session of full-mouth subgingival instrumentation using a piezoceramic ultrasonic device ( EMS PiezonMaster 400 , A+PerioSlim tips ) with water coolant ( Fm-UD ) or quadrant scaling/root planing ( Q-SRP ) with h and instruments . At 3 months , all sites with remaining PPD > or = 5 mm were subjected to repeated debridement with either the ultrasonic device or h and instruments . Plaque , PPD , relative attachment level ( RAL ) and bleeding following pocket probing ( BoP ) were assessed at baseline , 3 and 6 months . Primary efficacy variables were percentage of " closed pockets " ( PPD < or = 4 mm ) , and changes in BoP , PPD and RAL . RESULTS The percentage of " closed pockets " was 58 % at 3 months for the Fm-UD approach and 66 % for the Q-SRP approach ( p>0.05 ) . Both treatment groups showed a mean reduction in PPD of 1.8 mm , while the mean RAL gain amounted to 1.3 mm for Fm-UD and 1.2 mm for Q-SRP ( p>0.05 ) . The re-treatment at 3 months result ed in a further mean PPD reduction of 0.4 mm and RAL gain of 0.3 mm at 6 months , independent of the use of ultrasonic or h and instruments . The efficiency of the initial treatment phase ( time used for instrumentation/number of pockets closed ) was significantly higher for the Fm-UD than the Q-SRP approach : 3.3 versus 8.8 min . per closed pocket ( p<0.01 ) . The efficiency of the re-treatment session at 3 months was 11.5 min . for ultrasonic and 12.6 min . for h and instrumentation ( p>0.05 ) . CONCLUSION The results demonstrated that a single session of Fm-UD is a justified initial treatment approach that offers tangible benefits for the chronic periodontitis patient OBJECTIVES To determine the clinical effects of full mouth compared with quadrant wise scaling and root planing . METHOD Twenty patients with chronic periodontitis ( > or = 2 teeth per quadrant with probing pocket depths ( PPD ) > or = 5 mm and bleeding on probing ( BOP ) were r and omized into a test group treated in two sessions with subgingival scaling and root planing within 24 h ( full-mouth root planing ( FMRP ) ) and a control group treated quadrant by quadrant in four sessions in intervals of 1 week ( quadrant root planing ( QRP ) ) . PPD , relative attachment level ( RAL ) and BOP were recorded at baseline , 3 and 6 months . RESULTS Analysing first quadrant data , in moderately deep pockets ( 5 mm < or = PPD < 7 mm ) there was no evidence for a difference ( FMRP-QRP ) between both groups for PPD reduction ( mean : -0.128 mm ; CI : [ -0.949 , 0.693 ] ; p=0.747 ) , RAL gain ( mean : 0.118 mm ; CI : [ -0.763 , 1.000 ] ; p=0.781 ) , and BOP reduction ( mean : -20.1 % ; CI : [ -44.3 , 4.2 ] ; p=0.099 ) . Likewise , no significant differences between treatments were found for initially deep pockets ( PPD > or = 7 mm ) , neither for first quadrant nor for whole mouth data . CONCLUSION The results of the present study demonstrated equally favourable clinical results following both treatment modalities BACKGROUND A st and ard treatment strategy for periodontal infections often consists of 4 consecutive sessions of scaling and root planing ( per quadrant , at 1- to 2-week intervals ) , without proper disinfection of the remaining intra-oral niches for periodontopathogens . This could theoretically lead to a reinfection of previously disinfected pockets by bacteria from an untreated region/niche . This study aim ed to investigate , over an 8-month period , the clinical benefits of a one stage full-mouth disinfection in the control of severe periodontitis . METHODS Sixteen patients with early-onset periodontitis and 24 patients with severe adult periodontitis were r and omly assigned to test and control groups . The control group was scaled and root planed , per quadrant , at 2-week intervals and given st and ard oral hygiene instructions . A one stage full-mouth disinfection ( test group ) was sought by scaling and root planing the 4 quadrants within 24 hours in combination with the application of chlorhexidine to all intra-oral niches for periodontopathogens . Besides oral hygiene , the test group also rinsed twice daily with a 0.2 % chlorhexidine solution and sprayed the tonsils with a 0.2 % chlorhexidine spray , for 2 months . The plaque index , gingival index , probing depth , bleeding on probing , gingival recession , and clinical attachment level were recorded at baseline and at 1 , 2 , 4 , and 8 months afterwards . RESULTS The one stage full-mouth disinfection result ed , in comparison to the st and ard therapy , in a significant ( P < 0.001 ) additional probing depth reduction and gain in attachment up to 8 months . For initial pockets > or = 7 mm , the " additional " probing depth reduction at the 8 month follow-up was 1.2 mm for single-rooted and 0.9 mm for multi-rooted teeth , with corresponding additional gains in attachment of 1.0 mm and 0.8 mm , respectively . The additional improvements were observed for all subgroups ( adult periodontitis , generalized early-onset cases , smokers ) , with the largest differences in the non-smoking adult periodontitis patients . CONCLUSIONS These findings suggest that a one stage full-mouth disinfection results in an improved clinical outcome for the treatment of chronic adult or early-onset periodontitis as compared to scaling and root planing per quadrant at 2-week intervals |
2,255 | 16,235,318 | In these trials , systemic local anesthetics were safe , with no deaths or life-threatening toxicities .
Lidocaine and oral analogs were safe drugs in controlled clinical trials for neuropathic pain , were better than placebo , and were as effective as other analgesics .
More emphasis is necessary on outcomes measuring patient satisfaction to assess if statistically significant pain relief is clinical ly meaningful | BACKGROUND Lidocaine , mexiletine , tocainide , and flecainide are local anesthetics which give an analgesic effect when administered orally or parenterally .
Early reports described the use of intravenous lidocaine or procaine to relieve cancer and postoperative pain ( Keats 1951 ; Gilbert 1951 ; De Clive-Lowe 1958 ; Bartlett 1961 ) .
Interest reappeared decades later when patient series and clinical trials reported that parenteral lidocaine and its oral analogs tocainide , mexiletine , and flecainide relieved neuropathic pain in some patients ( Boas 1982 ; Lindblom 1984 ; Petersen 1986 ; Dunlop 1988 ; Bach 1990 ; Awerbuch 1990 ) .
With the recent publication of clinical trials with high quality st and ards , we have review ed the use of systemic lidocaine and its oral analogs in neuropathic pain to up date our knowledge , to measure their benefit and harm , and to better define their role in therapy .
OBJECTIVES To evaluate pain relief and adverse effect rates between systemic local anesthetic-type drugs and other control interventions . | Background : Pain following spinal cord injury ( SCI ) is a therapeutic challenge . Only a few treatments have been assessed in r and omized , controlled trials . The primary objective of the present study was to examine the analgesic effect of ketamine and lidocaine in a group of patients with neuropathic pain below the level of spinal cord injury . We also wanted to assess sensory abnormalities to see if this could help us to identify responders and if treatments result ed in changes of sensibility Background Several lines of evidence suggest that neuropathic pain ( including Complex Regional Pain Syndrome [ CRPS ] I and CRPS II ) is mediated in part by an increase in the density of voltage-sensitive sodium channels in injured axons and the dorsal root ganglion of injured axons . This study sought to characterize the effects of intravenous lidocaine ( a sodium channel blocker ) on acute sensory thresholds within the painful area and the size of the painful area in patients suffering from CRPS I and II . Methods This study used a r and omized , double-blind , placebo-controlled design in 16 subjects suffering from CRPS I and II with a prominent allodynia . Each subject received an intravenous infusion of lidocaine and diphenhydramine separated by 1 week . A computer-controlled infusion pump targeted stair-step increases in plasma levels of lidocaine of 1 , 2 , and 3 & mgr;g/ml . At baseline and at each plasma level , spontaneous and evoked pain scores and neurosensory testing within the painful area were measured . The neurosensory testing consisted of thermal thresholds , tactile thresholds and the area of allodynia to punctate , and stroking and thermal stimuli . Results Intravenous lidocaine and diphenhydramine had no significant effect on the cool , warm , or cold pain thresholds . However , lidocaine caused a significant elevation of the hot pain thresholds in the painful area . Intravenous lidocaine caused a significantly decreased response to stroking and cool stimuli in the allodynic area . There was also a significant decrease in pain scores to cool stimuli at all plasma levels and the spontaneous pain at the highest plasma level . Conclusions This study demonstrates that intravenous lidocaine affects pain in response to cool stimuli more than mechanical pain in subjects with neuropathic pain . There is a lesser effect on spontaneous pain and pain induced by stroking stimuli and no effect on the pain induced by punctate stimuli & NA ; In a double‐blind controlled design , 7 patients with painful diabetic neuropathy received lidocaine 5 mg/kg or saline intravenously over a period of 30 min . Thermal sensibility quantified by thermotest was not affected by lidocaine . In 3 of the patients nociceptive flexion reflex thresholds could be determined . The threshold was increased by lidocaine and returned to pre‐infusion level within 10 days . Lidocaine also increased the threshold in 4 healthy subjects , but did not affect the Hoffmann reflex . These results suggest that lidocaine exerts its pain‐relieving effect on the spinal level in diabetic neuropathy In a few uncontrolled studies intravenous lidocaine has been used in the treatment of chronic pain . In a controlled study we used intravenous lidocaine in 18 patients with severe chronic pain states due to various but mainly neurological diseases . After the infusion of lidocaine 14 patients ( 78 % ) had significant pain relief ranging from 2 hours to 25 days . There was no significant effect of placebo infusion with isotonic saline . The mechanism of the pain relieving ability of intravenous lidocaine is unknown Background and Objectives Mexiletine is a sodium channel blocker that has been used for the treatment of a variety of neuropathic pain syndromes . A recent double-blinded placebo-controlled study concluded that it was ineffective in the treatment of allodynia associated with neuropathic pain . However , this study failed to achieve adequate plasma levels of mexiletine . This was a study in healthy volunteers that sought to push the drug to dose-limiting side effects and then evaluate the effects on human experimental pain . Methods Twelve healthy volunteers were studied using a r and omized , double-blind , placebo-controlled crossover study . The subjects were titrated to a maximum dose of 1,350 mg/d or dose-limiting side effects , whichever occurred first . At baseline and day 10 and 17 , neurosensory testing , train-of-three thermal pulses , and side-effect measurements were performed and on day 17 , intradermal capsaicin was injected on the volar aspect of the forearm and the pain and secondary hyperalgesia to von Frey hair , stroking , and thermal stimuli were measured . Results Peak plasma levels occurred on day 10 and were 0.36 ± 0.21 μg/mL. All subjects experienced dose-limiting side effects . The mean maximum tolerable daily dose achieved was 859 mg ( range , 300 to 1,350 mg ) . The side effects reported by the subjects included nausea , lightheadedness , muscle twitching and weakness , blurred vision , headache , tremors , difficulty concentrating , dysphoria , sedation , pruritis , and rash . These side effects occurred at an average daily dose of 993 mg ( range , 600 to 1,350 mg ) . Compared with placebo , mexiletine had no significant effects on any of the neurosensory thresholds and pain scores after intradermal capsaicin . There was a significant reduction in the area of secondary hyperalgesia to von Frey hair stimulation only . There was a significant correlation between plasma mexiletine level and flare response . Conclusions Mexiletine has minimal effects on human experimental pain . It is severely limited by side effects and tolerable doses seem to be void of effects on normal neurosensation and facilitated pain induced by capsaicin and thermal heat pulses Background and Objectives Mexiletine is an oral sodium channel antagonist that has been reported to be effective in a variety of neuropathic pain syndromes . However , recent reports question the efficacy of oral mexiletine in neuropathic pain . The objectives of this study were to examine the effect of oral mexiletine on pain , neurosensation , allodynia , and quality of life . Methods Twenty subjects suffering from neuropathic pain with prominent allodynia were enrolled in a r and omized placebo-controlled crossover study . Patients were titrated to a maximum dose of 900 mg/d or doselimiting side effects , whichever occurred first . At baseline and on days 0 , 4 , 7 , and 10 , the following tests were performed : ( 1 ) Quality of Life Question naires ; ( 2 ) pain scores ; ( 3 ) area of allodynia ; ( 4 ) side effects ; ( 5 ) neurosensory testing ; and ( 6 ) peak and trough plasma mexiletine levels . Results Peak plasma levels occurred on day 10 and were 0.54 μg/mL. There was no significant effect on any quality of life measurement . There was no significant effect on any neurosensory threshold or the area of allodynia . There was a significant effect of mexiletine on stroking-induced pain . There were no significant effects on any other pain score . Side effects were negligible . Conclusions At doses of up to 900 mg/d , mexiletine has minimal effects on pain and allodynia of neuropathic pain . However , side effects may preclude higher doses & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies & NA ; Ten patients with organic nerve injury causing chronic neuropathic pain were tested for the effects of intravenous lidocaine versus saline upon psychophysical somatosensory variables . The variables assessed were the subjective magnitude of pain , area of mechanical hyperalgesia and presence and magnitude of thermal heat/cold hyperalgesia . The study methods applied to evaluate these conditions were the conventional testing of somatosensory submodalities with area mapping and the subjective magnitude estimation of spontaneous pain . It was found that spontaneous pain and mechanical hyperalgesia were consistently improved , transiently , by intravenous administration of lidocaine in all 10 patients ; areas of hyperalgesia which extended beyond the territory of the nerve also improved transiently . Spontaneous pain and mechanical hyperalgesia , but not hypoesthesia , were transiently improved by injection of saline in only 1 of the 10 patients . This outcome is probably due to a placebo effect . This improvement is in keeping with the inhibition of anomalous neural impulses which can be generated anywhere along the sensory channels responsible for generating spontaneous pain and hyperalgesia . Thus , intravenous lidocaine is proposed as a diagnostic aid in the examination of patients complaining of complex sensory disorders associated with nerve injury . The transient pain relief may allow a fuller identification of the area of sensory loss Severe pain occurs in 5 - 30 % of the spinal cord-injured ( SCI ) population and is difficult to treat . Subarachnoid lidocaine has been used in selected patients with some success . Mexiletine , an analog of lidocaine that acts at Na+/K+ channels in the peripheral nerve , has been found effective in persons with diabetic dysesthetic neuropathy . The effect of mexiletine in the treatment of spinal cord dysesthetic pain was examined in this study . Fifteen patients were enrolled , and 11 patients completed the prospect i ve , r and omized , placebo-controlled , double-blind , crossover design trial . Inclusion /exclusion criteria were carefully defined . A 1-wk washout period was followed by a 4-wk drug trial of either mexiletine ( 450 mg/day ) or placebo . This was repeated for the second medication in the second arm of the study . Patients were followed weekly with McGill and visual analog pain scales . Baseline , midpoint , and endpoint Barthel function scores were recorded . The Wilcoxon 's signed-rank test and paired t test were used for statistical analysis . Results showed no significant effect of mexiletine on SCI dysesthetic pain scales or Barthel index . In conclusion , in this trial , mexiletine did not appear to decrease spinal cord injury-related dysesthetic pain We studied the analgesic efficacy of an intravenous infusion of lidocaine and morphine in 19 adults with well-established postherpetic neuralgia in a three-session , r and omized , double-blind , placebo-controlled trial . Compared with saline placebo , both lidocaine and morphine reduced pain intensity . Reductions in pain did not correlate with side effects produced by the infusions . For morphine , there was a significant correlation between reductions in pain intensity and blood level achieved . In the majority of subjects who reported definite pain relief , allodynia also disappeared . The results show that neuropathic pain can respond to opioids and to systemically administered local anesthetic drugs The objective of this double-blind placebo controlled multicenter study was to prove the efficacy of mexiletine in painful diabetic neuropathy . Treatment was provided for in three dosages . For pain measurements a visual analogue scale ( VAS ) and McGill 's verbal rating scale were chosen . 95 patients were included . A global assessment of the VAS showed no differences in treatment . The total evaluation ( PRIT = Pain Rating Index Total ) of the McGill scale just failed the level of significance . More specific exploratory evaluation of subclasses of the McGill scale , representing different qualities of pain , gave remarkable differences between mexiletine and placebo . According to types of complaints an evaluation showed substantial advantages of the mexiletine treatment with both the VAS and the McGill scale . There is strong evidence that particularly patients with stabbing or burning pain , heat sensations or formication will benefit most by mexiletine therapy . Concerning the dosage , a medium regimen of 450 mg per day seems to be appropriate in this indication . With an increase in dosage the efficacy does not rise proportionally . Mexiletine proved a very safe therapy with negligible side effects at the medium dose range , even less than placebo . There were no cardiovascular side effects . Further investigations should pay more attention to the variety of the complaints and include the quality of life Although mexiletine , an antiarrhythmic with local anesthetic properties , has been reported to relieve discomfort in diabetic neuropathy , its usefulness in the treatment of HIV-related painful peripheral neuropathy ( PPN ) has not been determined . The tolerance and effectiveness of mexiletine in HIV-related PPN were assessed in 22 patients who were r and omized to receive mexiletine ( maximum dose , 600 mg/day ) or placebo for 6 weeks , followed by the alternative intervention for 6 weeks after a 1-week washout period . The daily pain response was assessed using a visual analogue scale card in 19 patients who received at least 2 weeks of the drug , 16 of whom were crossed-over to receive the alternate agent . No statistically significant difference was found between the mean daily pain scores for patients receiving mexiletine versus placebo , irrespective of the order in which the agents were received . Comparing the mean individual daily pain scores for each phase of study , 5 patients ( 31 % ) had significantly less pain while receiving mexiletine compared with their response to placebo , 5 patients ( 31 % ) had significantly less pain while receiving placebo , and no difference was noted in 6 patients ( 38 % ) . Crossover and multivariate analyses for repeated measures showed no apparent difference in the response to mexiletine versus placebo . Dose-limiting adverse events occurred in 39 % of those receiving mexiletine , but only 1 patient ( 5 % ) discontinued placebo . Mexiletine was only modestly well tolerated despite its relatively brief period of administration , and no evidence was found to support its benefit in HIV-related PPN . Although a first-drug effect was not demonstrated , a powerful placebo effect was seen in some patients This study investigated the effect of intravenous lidocaine at two doses ( 1 mg/kg and 5 mg/kg over 2 hours ) and an intravenous saline placebo on the pain and allodynia of postherpetic neuralgia ( PHN ) . Twenty-four patients were studied using a r and omized , double-blind , within-patient crossover design . Each patient received normal saline , lidocaine 0.5 mg/kg/h , and lidocaine 2.5 mg/kg/h for a 2-h period . The McGill Pain Question naire Short Form , visual analogue scores ( VAS ) , and area of allodynia were measured at intervals during the infusions . Free plasma lidocaine levels were also measured . The results were statistically analyzed using Student 's t-test for paired data . The VAS for ongoing pain showed a significant reduction after all the infusions ( P < 0.05 ) . For dynamic pressure-provoked pain , the VAS was unaffected by placebo but showed a reduction at an equal level of significance with both lidocaine infusions ( P < 0.05 ) . The area of allodynia of PHN , as mapped by brush stroke , declined in association with intravenous lidocaine ( 0.5 mg/kg/h = P < 0.05 ; 2.5 mg/kg/h = P < 0.001 ) . Placebo had no significant effect on the area of allodynia . These findings demonstrate a positive effect on pain and allodynia following a brief intravenous infusion of lidocaine . The higher dose infusion may produce plasma levels in the toxic range , with no significant clinical increase in response Sixteen of nineteen patients completed a r and omised double-blind crossover trial to assess the effect of oral mexiletine ( 10 mg/kg bodyweight daily ) on the symptoms and signs of chronic painful diabetic neuropathy . The median age of the sixteen patients was 50 years ( range 30 - 64 ) . Assessment with a five-item clinical symptom scale showed significant improvement during the mexiletine phase compared with the placebo phase . Pain was reduced during mexiletine but not during placebo , as assessed by a visual analogue rating scale . Mexiletine treatment had no effect on tendon reflexes , vibration threshold levels , beat-to-beat variation in heart rate during deep breathing , and postural blood pressure response . Mild side-effects were seen in three of the sixteen patients during mexiletine treatment Objective : To investigate the effects of systemic administration of lidocaine on different components of neuropathic central pains by quantitative sensory testing . Methods : The efficacy of systemic lidocaine ( 5 mg/kg IV over 30 minutes ) was evaluated in a double-blind , placebo-controlled , and cross-over fashion , on both spontaneous ongoing pain and evoked pains ( allodynia and hyperalgesia ) in 16 patients with chronic poststroke ( n = 6 ) or spinal cord injury ( n = 10 ) related pain . Results : Lidocaine was significantly superior to the placebo ( saline ) in reducing the intensity of spontaneous ongoing pain for up to 45 minutes after the injection : 10 of 16 patients ( 62.5 % ) receiving lidocaine showed a significant reduction in spontaneous pain , whereas only six patients showed this after the placebo . Lidocaine also significantly reduced the intensity of brush-induced allodynia and mechanical hyperalgesia , but was no better than the placebo against thermal allodynia and hyperalgesia . In general , the side effects were moderate and consisted mainly of lightheadedness ( 44 % ) . Conclusions : Systemic lidocaine can induce a significant and selective reduction of several components of pain caused by CNS injuries . The observed preferential antihyperalgesic and antiallodynic effects of this drug suggest a selective central action on the mechanisms underlying these evoked pains OBJECTIVE : To evaluate the efficacy and safety of mexiletine in the symptomatic treatment of diabetic peripheral neuropathy ( DPN ) . METHODS : In this prospect i ve , double-blind study , 29 patients were r and omized to receive mexiletine 600 mg/d or matching placebo for 3 weeks . A four-item symptom score ( FIS ) , which rated pain , dysesthesias , paresthesias , and nightly exacerbations of symptoms , and a 100-mm visual analog scale ( VAS ) , which rated pain intensity , were completed by patients before and after treatment . At the end of treatment independent patient and investigator global assessment s were made . Patients reported adverse effects after 1 and 3 weeks of treatment . RESULTS : Treatment groups were similar at baseline . The difference between the median changes in FIS scores ( mexiletine = 5.5 , placebo = 2 ) was not statistically significant . Overall symptom response was similar in both treatment groups as demonstrated by both global assessment s ( p = 0.19 ) . The mean change in VAS score from baseline to posttreatment was determined for both groups and the difference between these mean scores was 16.5 mm ( 95 % CI , −7.1 to 40.2 mm ) ( p = 0.16 ) . Inadequate statistical power ( 1 — β = 0.40 ) may have result ed from small sample size , small magnitude of effect , or variability in the measured effect . Adverse effects were more common in the mexiletine group , though not statistically significant . One patient receiving mexiletine was hospitalized for palpitations . CONCLUSIONS : Because of conflicting reports of mexiletine 's efficacy in the treatment of symptomatic DPN , this drug should be reserved for patients unresponsive or intolerant to st and ard therapy , without evidence of heart disease , and with sensations of burning , heat , formication , or stabbing pain Objective : To investigate the effects of IV lidocaine on spontaneous and evoked pain ( allodynia and hyperalgesia ) due to peripheral nerve injury ( postherpetic neuralgia or nerve trauma ) using quantitative sensory testing . Method : The authors r and omized 22 patients to receive lidocaine 5 mg/kg IV during 30 minutes or placebo in a double-blind crossover design and 16 patients subsequently received mexiletine on an open basis titrated from 400 to 1,000 mg per day ( mean 737 mg/day ) . Results : Lidocaine induced a significant decrease in ongoing pain for up to 6 hours with a peak effect 60 to 120 minutes postinjection . The drug also decreased mechanical dynamic allodynia and static ( punctate ) mechanical allodynia/hyperalgesia , but not thermal allodynia and hyperalgesia . The effects of lidocaine and mexiletine on spontaneous pain intensity were significantly higher in patients with concomitant mechanical allodynia in comparison with those without allodynia . Conclusions : These data indicate modality-specific antihyperalgesic effects of IV lidocaine in patients with peripheral nerve injury . Patients with mechanical allodynia may be good c and i date s for treatment with local anesthetic-like drugs and possibly with other sodium-channel blockers In a r and omized double-blind , cross-over study the effect of intravenous lidocaine ( 5 mg/kg body weight ) on the symptoms and signs of painful diabetic neuropathy of more than 6 months duration has been evaluated . Using a clinical symptom scale , there was significant beneficial effect 1 and 8 days after lidocaine infusion compared to after saline infusion ( P less than 0.05 and P less than 0.02 , respectively ) . The duration of the individual effect ranged from 3 to 21 days . Lidocaine infusion had no effect on the objective measurements of neuropathy . Intravenous lidocaine infusion seems to be a new alternative treatment of chronic painful diabetic neuropathy Basic research indicates that systemic local‐anaesthetic‐type drugs that block sodium channels are effective in pain due to nerve damage . These drugs were first used as analgesics in the 1950s and they are still commonly used to try to relieve neuropathic pain and incident pain caused by cancer . As they are potentially toxic , these drugs should not be used without proven effectiveness . For these reasons , a systematic review of r and omized controlled trials of systemically administered local‐anaesthetic‐type drugs in chronic pain was performed . Main outcomes were pain relief or pain intensity difference and adverse effects . Twenty‐one reports were found , and four publications were excluded . In the remaining 17 studies ( 450 patients ) , 10 used intravenous lignocaine , two used intranasal lignocaine , four used oral mexiletine and one used oral tocainide Although effective in neuropathic pain , the efficacy of systemic lidocaine in non-neuropathic pain remains uncertain . We investigated the analgesic effect of systemic lidocaine on the heat/capsaicin sensitization model of experimental pain in 24 volunteers . Sensitization was produced by heating the skin to 45 ° C for 5 min , followed by a 30-min application of 0.075 % capsaicin cream , and maintained by periodically reheating the sensitized skin . Subjects received IV lidocaine ( bolus 2 mg/kg , then infusion 3 mg · kg · h ) , or saline for 85 min . Areas of secondary hyperalgesia , heat pain detection thresholds , and painfulness of stimulation with 45 ° C for 1 min ( long thermal stimulation ) were quantified . Systemic lidocaine reduced the area of secondary hyperalgesia to brush , but not to von Frey hair stimulation . Lidocaine did not alter heat pain detection thresholds or painfulness of long thermal stimulation in normal skin . We conclude that , at infusion rates in the low- to mid-antiarrhythmic range , lidocaine has no effect on acute nociceptive pain but does have a limited and selective effect on secondary hyperalgesia . Implication s The efficacy of systemic lidocaine in nonneuropathic pain remains uncertain . This study investigates the effect of systemic lidocaine on experimental-induced hyperalgesia in 25 volunteers . Hyperalgesia was induced by using an experimental pain model that uses heat and capsaicin in combination . Systemic lidocaine showed a selective effect on secondary hyperalgesia OBJECTIVE To assess the reliability of an augmented SF-36 instrument , the Treatment Outcomes in Pain Survey ( " TOPS " ) , in patients treated in two pain management programs , and present norms for initial values and treatment-related improvements . DESIGN Prospect i ve case series at two sites with longitudinal follow-up . SETTING Multidisciplinary , comprehensive outpatient pain treatment centers in university hospitals in Salt Lake City and Boston . PATIENTS Nine hundred and forty seven adult out patients with a range of socioeconomic , demographic , and ethnic characteristics , all referred for evaluation and treatment of chronic pain . INTERVENTIONS Usual practice multidisciplinary pain treatment . OUTCOMES MEASURES TOPS prior to pain treatment and 5-week nominal follow-up . Means and st and ard deviations of baseline and follow-up results . Psychometric results for reliability ( Cronbach alpha ) , validity ( item discriminant validity , validity coefficients ) , and related statistical precision measures for group and individual design s. RESULTS Several measures were precise enough to permit following individual patients in st and ard clinic treatment , of which the Total Pain Experience dimension was the most powerful . Similar psychometrics were observed in the Boston and Salt Lake City sites . The Pain Symptom , Objective Family/Social Disability , Objective Work Disability , and Upper Body Functional Limitations scales were vali date d. DISCUSSION The TOPS was design ed to satisfy several models of clinical pain treatment . It successfully monitored treatment based on those models . Not all patients improve with treatment , but most do . The TOPS can be administered in a variety of ways , but we found paper and pencil administration with computer scanning of results quick and efficient for making the data available to clinicians as part of treatment . CONCLUSIONS The accuracy of the TOPS is sufficient to monitor the response of individual patients during multidisciplinary treatment of chronic pain . The TOPS provides needed documentation ( e.g. , to third-party payors ) of the aggregate value of multidisciplinary outpatient treatment of chronic pain as well as its benefit for individual patients The management of patients with neuropathic pain is challenging . There are only a few reports regarding the acute effects of the commonly used adjuvant drugs amitriptyline ( AMI ) , gabapentin ( GBP ) , and lidocaine ( LDC ) on neuropathic pain behaviors in animal models . Thus , the purpose of this study was to investigate the acute effects of AMI , GBP , and LDC on behavioral signs of mechanical allodynia and the site of action of these drugs using a rat model of neuropathic pain . Under general anesthesia with halothane , neuropathic injury was produced in rats by tightly ligating the left L5 and L6 spinal nerves . In Experiment 1 , baseline mechanical allodynia data were recorded , and the animals were r and omly divided into five groups : Group 1 received saline intraperitoneally ( IP ) , Group 2 received AMI ( 1.5 mg/kg IP ) ; Group 3 received GBP ( 50 mg/kg IP ) , Group 4 received an IV saline infusion for 10 min , and Group 5 received LDC ( 10-mg/kg IV infusion ) for 10 min . Measurements of mechanical allodynia were repeated 0.5 , 1 , 2 , and 4 h and 1 , 3 , and 7 days after treatment . In Experiment 2 , rats were prepared similarly to the first experiment , and a single unit activity of continuous discharges of injured afferent fibers was recorded from the left L5 fascicles before and until 1 h after treatment . All animals developed neuropathic pain behavior within 7 days after surgery . All three tested drugs were effective in increasing the threshold for mechanical allodynia as early as 30 min after treatment , and the effect lasted for at least 1 h. Furthermore , AMI and LDC reduced the rate of continuing discharges of injured afferent fibers , whereas GBP did not influence these discharges . Our findings clearly demonstrate an attenuation of neuropathic pain behavior in rats treated with AMI , GBP , or LDC . Finally , the site of action of LDC seems to be primarily in the periphery , and that of GBP is exclusively central , whereas that of AMI seems to have both peripheral and central components . Implication s : In the present study , we examined the effectiveness of three drugs commonly used for the treatment of neuropathic pain . Systemic injections of amitriptyline , gabapentin , or lidocaine produced pain-relieving effects in this established model for neuropathic pain in rats , which supports their clinical use in managing patients with neuropathic pain syndromes . ( Anesth Analg 1998;87:1360 - 6 & NA ; The purpose of this study was to determine the levels of change on st and ard pain scales that represent clinical ly important differences to patients . Data from analgesic studies are often difficult to interpret because the clinical importance of the results is not obvious . Differences between groups , as summarized by a change in mean values over time , can be difficult to apply to clinical care . Baseline scores vary widely and group mean differences could reflect large changes in a few patients , small changes in many patients , or any combination of these outcomes . Determination of the proportion of patients who have a clinical ly important improvement in their pain would provide a more interpretable result with direct clinical implication s. However , determining a clinical ly important outcome requires information about the degree of change over time that is clinical ly important . Data from the titration phase of a multiple cross‐over r and omized clinical trial of oral transmucosal fentanyl citrate ( OTFC ) for the treatment of cancer‐related breakthrough pain were re‐analyzed to examine the differences in pain scores between treatment episodes that did and did not yield adequate pain relief . The scales evaluated were absolute pain intensity difference ( PID , 0–10 scale ) , percentage pain intensity difference ( PID% , 0–100 % scale ) , pain relief ( PR , 0 ( none ) , 1 ( slight ) , 2 ( moderate ) , 3 ( lots ) , 4 ( complete ) ) , sum of the pain intensity difference ( SPID over 60 min ) , percentage of maximum total pain relief ( % Max TOTPAR over 60 min ) , and global medication performance ( 0 ( poor ) , 1 ( fair ) , 2 ( good ) , 3 ( very good ) , 4 ( excellent ) ) . Adequate relief was defined by the patient 's decision not to use another dose of opioid medication as a rescue , in addition to the study medication , to treat each painful episode . One hundred thirty OTFC naive patients contributed data on 1268 episodes of breakthrough pain . The scales that were converted to a percentage change yielded the best accuracy in predicting adequate relief , with balanced sensitivity and specificity . The best cut‐off point for both the % Max TOTPAR and the PID% was 33 % . The best cut‐off points for the absolute scales were absolute pain intensity difference of 2 , pain relief of 2 ( moderate ) , and SPID of 2 . The global medication performance of 2 ( good ) had excellent values as well . This study presents data ‐derived cut‐off points for the changes in several pain scales , each reflecting the clinical ly important improvement for patients treating breakthrough cancer pain episodes with OTFC . Confirmation in other patient population s and different pain syndromes will be needed . The use of consistent clinical ly important cut‐off points as the primary outcome in future pain therapy clinical trials will enhance their validity , comparability , and clinical applicability BACKGROUND AND OBJECTIVES Sciatica is a neuropathic pain syndrome caused by compression and /or inflammation of spinal nerve roots by herniated disc material , and its treatment is therefore usually aim ed at reducing compression and inflammation . Studies have shown that both systemic local anesthetics and N-methyl-D-aspartate ( NMDA ) receptor antagonists may produce analgesia in a variety of neuropathic pain syndromes . The present study evaluated the analgesic efficacy of i.v . infusions of the local anesthetic lidocaine , the NMDA receptor antagonist amantadine , and a placebo in sciatica . METHODS Thirty patients with sciatica , as confirmed by physical examination and imaging studies , were enrolled in a r and omized , double-blind , three-arm crossover trial . Infusions of amantadine ( 2.5 mg/kg ) , lidocaine ( 5 mg/kg ) , and a placebo were administered over a 2-hour period , 2 - 7 days apart from each other . Spontaneous pain ( visual analog scale ) and evoked pain ( straight leg raise ) were measured every 30 minutes for 3 hours . RESULTS Lidocaine reduced spontaneous pain as compared with amantadine and with the placebo for all measurements and at a significant level at the 30 ( P < .05 ) , 120 , and 180 ( P < .01 ) minute time points . Maximal pain reduction from the baseline was 62 + /- 7 % for lidocaine , 43 + /- 7 % for amantadine , and 47 + /- 7 % for the placebo . Straight leg raise test also significantly improved with lidocaine ( from 30 to 37 degrees ; P < .05 ) , as compared to amantadine ( 34 - 36 degrees ) and to the placebo ( 32 - 34 degrees ) . All three treatments were relatively well tolerated . CONCLUSIONS Intravenous lidocaine , rather than amantadine , reduces both spontaneous and evoked sciatic pain The proposed practice of " evidence -based medicine , " which calls for careful clinical judgment in evaluating the " best available evidence , " should be differentiated from the special collection of data regarded as suitable evidence . Although the proposed practice does not seem new , the new collection of " best available " information has major constraints for the care of individual patients . Derived almost exclusively from r and omized trials and meta-analyses , the data do not include many types of treatments or patients seen in clinical practice ; and the results show comparative efficacy of treatment for an " average " r and omized patient , not for pertinent subgroups formed by such cogent clinical features as severity of symptoms , illness , co-morbidity , and other clinical nuances . The intention-to-treat analyses do not reflect important post-r and omization events leading to altered treatment ; and the results seldom provide suitable background data when therapy is given prophylactically rather than remedially , or when therapeutic advantages are equivocal . R and omized trial information is also seldom available for issues in etiology , diagnosis , and prognosis , and for clinical decisions that depend on pathophysiologic changes , psychosocial factors and support , personal preferences of patients , and strategies for giving comfort and reassurance . The laudable goal of making clinical decisions based on evidence can be impaired by the restricted quality and scope of what is collected as " best available evidence . " The authoritative aura given to the collection , however , may lead to major abuses that produce inappropriate guidelines or doctrinaire dogmas for clinical practice A quantitative systematic review , or meta- analysis , uses statistical methods to combine the results of multiple studies . Meta-analyses have been done for systematic review s of therapeutic trials , diagnostic test evaluations , and epidemiologic studies . Although the statistical methods involved may at first appear to be mathematically complex , their purpose is simple : They are trying to answer four basic questions . Are the results of the different studies similar ? To the extent that they are similar , what is the best overall estimate ? How precise and robust is this estimate ? Finally , can dissimilarities be explained ? This article provides some guidance in underst and ing the key technical aspects of the quantitative approach to these questions . We have avoided using equations and statistical notations ; interested readers will find implementations of the described methods in the listed references . We focus here on the quantitative synthesis of reports of r and omized , controlled , therapeutic trials because far more meta-analyses on therapeutic studies than on other types of studies have been published . For practical reasons , we present a stepwise description of the tasks that are performed when statistical methods are used to combine data . These tasks are 1 ) deciding whether to combine data and defining what to combine , 2 ) evaluating the statistical heterogeneity of the data , 3 ) estimating a common effect , 4 ) exploring and explaining heterogeneity , 5 ) assessing the potential for bias , and 6 ) presenting the results . Deciding Whether To Combine Data and Defining What To Combine By the time one performs a quantitative synthesis , certain decisions should already have been made about the formulation of the question and the selection of included studies . These topics were discussed in two previous articles in this series [ 1 , 2 ] . Statistical tests can not compensate for lack of common sense , clinical acumen , and biological plausibility in the design of the protocol of a meta- analysis . Thus , a reader of a systematic review should always address these issues before evaluating the statistical methods that have been used and the results that have been generated . Combining poor- quality data , overly biased data , or data that do not make sense can easily produce unreliable results . The data to be combined in a meta- analysis are usually either binary or continuous . Binary data involve a yes/no categorization ( for example , death or survival ) . Continuous data take a range of values ( for example , change in diastolic blood pressure after antihypertensive treatment , measured in mm Hg ) . When one is comparing groups of patients , binary data can be summarized by using several measures of treatment effect that were discussed earlier in this series [ 3 ] . These measures include the risk ratio ; the odds ratio ; the risk difference ; and , when study duration is important , the incidence rate . Another useful clinical measure , the number needed to treat ( NNT ) , is derived from the inverse of the risk difference [ 3 ] . Treatment effect measures , such as the risk ratio and the odds ratio , provide an estimate of the relative efficacy of an intervention , whereas the risk difference describes the intervention 's absolute benefit . The various measures of treatment effect offer complementary information , and all should be examined [ 4 ] . Continuous data can be summarized by the raw mean difference between the treatment and control groups when the treatment effect is measured on the same scale ( for example , diastolic blood pressure in mm Hg ) , by the st and ardized mean difference when different scales are used to measure the same treatment effect ( for example , different pain scales being combined ) , or by the correlation coefficients between two continuous variables [ 5 ] . The st and ardized mean difference , also called the effect size , is obtained by dividing the difference between the mean in the treatment group and the mean in the control group by the SD in the control group . Evaluating the Statistical Heterogeneity of the Data This step is intended to answer the question , Are the results of the different studies similar ( homogeneous ) ? It is important to answer this question before combining any data . To do this , one must calculate the magnitude of the statistical diversity ( heterogeneity ) of the treatment effect that exists among the different sets of data . Statistical diversity can be thought of as attributable to one or both of two causes . First , study results can differ because of r and om sampling error . Even if the true effect is the same in each study , the results of different studies would be expected to vary r and omly around the true common fixed effect . This diversity is called the within- study variance . Second , each study may have been drawn from a different population , depending on the particular patients chosen and the interventions and conditions unique to the study . Therefore , even if each study enrolled a large patient sample , the treatment effect would be expected to differ . These differences , called r and om effects , describe the between- study variation with regard to an overall mean of the effects of all of the studies that could be undertaken . The test most commonly used to assess the statistical significance of between- study heterogeneity is based on the chi-square distribution [ 6 ] . It provides a measure of the sum of the squared differences between the results observed and the results expected in each study , under the assumption that each study estimates the same common treatment effect . A large total deviation indicates that a single common treatment effect is unlikely . Any pooled estimate calculated must account for the between- study heterogeneity . In practice , this test has low sensitivity for detecting heterogeneity , and it has been suggested that a liberal significance level , such as 0.1 , should be used [ 6 ] . Estimating a Common Effect The questions that this step tries to answers are , 1 ) To the extent that data are similar , what is their best common point estimate of a therapeutic effect , and 2 ) how precise is this estimate ? The mathematical process involved in this step generally involves combining ( pooling ) the results of different studies into an overall estimate . Compared with the results of individual studies , pooled results can increase statistical power and lead to more precise estimates of treatment effect . Each study is given a weight according to the precision of its results . The rationale is that studies with narrow CIs should be weighted more heavily than studies with greater uncertainty . The precision is generally expressed by the inverse of the variance of the estimate of each study . The variance has two components : the variance of the individual study and the variance between different studies . When the between- study variance is found to be or assumed to be zero , each study is simply weighted by the inverse of its own variance , which is a function of the study size and the number of events in the study . This approach characterizes a fixed-effects model , as exemplified by the Mantel-Haenszel method [ 7 , 8 ] or the Peto method [ 9 ] for dichotomous data . The Peto method has been particularly popular in the past . It has the advantage of simple calculation ; however , although it is appropriate in most cases , it may introduce large biases if the data are unbalanced [ 10 , 11 ] . On the other h and , r and om-effects models also add the between- study variance to the within- study variance of each individual study when the pooled mean of the r and om effects is calculated . The r and om-effects model most commonly used for dichotomous data is the DerSimonian and Laird estimate of the between- study variance [ 12 ] . Fixed- and r and om-effects models for continuous data have also been described [ 13 ] . Pooled results are generally reported as a point estimate and CI , typically a 95 % CI . Other quantitative techniques for combining data , such as the Confidence Profile Method [ 14 ] , use Bayesian methods to calculate posterior probability distributions for effects of interest . Bayesian statistics are based on the principle that each observation or set of observations should be viewed in conjunction with a prior probability describing the prior knowledge about the phenomenon of interest [ 15 ] . The new observations alter this prior probability to generate a posterior probability . Traditional meta- analysis assumes that nothing is known about the magnitude of the treatment effect before r and omized trials are performed . In Bayesian terms , the prior probability distribution is noninformative . Bayesian approaches may also allow the incorporation of indirect evidence in generating prior distributions [ 14 ] and may be particularly helpful in situations in which few data from r and omized studies exist [ 16 ] . Bayesian analyses may also be used to account for the uncertainty introduced by estimating the between- study variance in the r and om-effects model , leading to more appropriate estimates and predictions of treatment efficacy [ 17 ] . Exploring and Explaining Heterogeneity The next important issue is whether the common estimate obtained in the previous step is robust . Sensitivity analyses determine whether the common estimate is influenced by changes in the assumptions and in the protocol for combining the data . A comparison of the results of fixed- and r and om-effects models is one such sensitivity analysis [ 18 ] . Generally , the r and om-effects model produces wider CIs than does the fixed-effects model , and the level of statistical significance may therefore be different depending on the model used . The pooled point estimate per se is less likely to be affected , although exceptions are possible [ 19 ] . Other sensitivity analyses may include the examination of the residuals and the chi-square components [ 13 ] and assessment of the effect of deleting each study in turn . Statistically significant results that depend on a single study may require further exploration . Cumulative Meta- Analysis The local anesthetic sodium-channel blockers lidocaine and mexiletine reduce spontaneous and evoked activity in experimental neuroma models and have been reported to relieve a variety of clinical neuropathic pain conditions . The predictive value of relief from an intravenous lidocaine infusion ( IVL ) for subsequent relief from a 4-week trial of oral mexiletine was assessed in a prospect i ve study of nine subjects with chronic neuropathic pain of peripheral origin . Subjects received IVL , 2 mg/kg and 5 mg/kg , over 45 min during separate sessions in r and om order under double-blind conditions . One week later , a 4-week titrating trial of oral mexiletine was initiated . Both doses of IVL significantly reduced pain visual analogue scores ( VAS ) scores . Although IVL 5 mg/kg produced significantly higher pain relief scores than IVL 2 mg/kg , subjects responded in a highly consistent manner to the two IVL . Subsequent response to oral mexiletine was significantly correlated with the average response to the two IVL . Mexiletine dose and blood levels were not correlated with pain relief . The results suggest that IVL may be a valuable tool in selecting patients for oral therapy with analogous drugs Abstract Objective To determine whether poor reporting of methods in r and omised controlled trials reflects on poor methods . Design Observational study . Setting Reports of r and omised controlled trials conducted by the Radiation Therapy Oncology Group since its establishment in 1968 . Participants The Radiation Therapy Oncology Group . Outcome measures Content of reports compared with the design features described in the protocol s for all r and omised controlled trials . Results The method ological quality of 56 r and omised controlled trials was better than reported . Adequate allocation concealment was achieved in all trials but reported in only 42 % of papers . An intention to treat analysis was done in 83 % of trials but reported in only 69 % of papers . The sample size calculation was performed in 76 % of the studies , but reported in only 16 % of papers . End points were clearly defined and α and βerrors were prespecified in 76 % and 74 % of the trials , respectively , but only reported in 10 % of the papers . The one exception was the description of drop outs , where the frequency of reporting was similar to that contained in the original statistical files of the Radiation Therapy Oncology Group . Conclusions The reporting of method ological aspects of r and omised controlled trials does not necessarily reflect the conduct of the trial . Review ing research protocol s and contacting trialists for more information may improve quality assessment Dans 11 cas sur 15 l'injection i.v . de lidocaine amene une sedation importante de la douleur et des troubles . Les effets ne sont pas expliques par des modifications metaboliques . Il pourrait s'agir , comme dans le cas des arythmies cardiaques , de deconnection de circuits nerveux We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked ( dynamic ) pain and punctate-evoked ( static ) hyperalgesia induced by capsaicin . In a r and omized , double-blind , placebo-controlled , crossover study , we studied 12 volunteers in three experiments . Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v . infusion of ketamine ( bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1 ) , lidocaine 5 mg kg-1 or saline for 50 min . Infusion started 15 min after injection of capsaicin . The following were measured : spontaneous pain , pain evoked by punctate and brush stimuli ( VAS ) , and areas of brush-evoked and punctate-evoked hyperalgesia . Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain . Lidocaine reduced the area of punctate-evoked hyperalgesia significantly . It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain . The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms and have a distinct pharmacology OBJECTIVE To investigate the efficacy and safety of mexiletine in the treatment of painful diabetic neuropathy . RESEARCH DESIGN AND METHODS A total of 216 insulin-treated diabetes patients with painful diabetic neuropathy were r and omly allocated to three dosages of mexiletine or placebo . The Visual Analog Scale ( VAS ) for pain/discomfort was scored each day during daytime and nighttime , and sleeping disturbances were also recorded by the patients . Plasma levels of mexiletine and 24-h electrocardiogram ( ECG ) mapping were assessed before and during the 3-week study period . RESULTS A significant reduction in sleep disturbances and pain during nighttime was observed in the group of patients taking the highest dosages ( 675 mg/day ) of mexiletine compared with the other groups . No significant correlation was found between plasma concentration of mexiletine and the therapeutic effect or adverse events . No serious adverse events were seen . The 24-h ECG mapping did not disclose onset of significant arrhythmias in any patient . CONCLUSIONS Mexiletine in a dosage of 675 mg daily can reduce pain caused by diabetic neuropathy , and the effect of this drug appears to have a rapid onset Abstract : In 10 cancer patients with cutaneous allodynia , intravenous lidocaine ( 5 mg/dg/ body weight ) or 0.9 % NaCI was given in a double blind cross-over study to determine the analgesic effect . One patient had complete and one had partial pain relief with lidocaine infusion , whereas three patients experienced partial pain relief with placebo . Neither lidocaine nor placebo reduced pain intensity or consumption of analgesics significantly during the study period . Intravenous infusion of lidocaine can not be recommended as routine pain treatment in cancer patients with cutaneous allodynia or pain , but further studies are needed to test the effects of lidocaine on different peripheral Neuropathic pain is often a difficult condition to treat . Clinical and laboratory studies using intravenously administered local anesthetics or antiarrhythmic agents support the use of these drugs for the treatment of neuropathic pain . The availability of the oral antiarrhythmic medication , mexiletine , has made it possible to study the effects of an orally administered medication on chronic neuropathic pain . The study used a double-blind placebo-controlled design to examine 11 subjects in whom treatment with conventional pain medications had been unsuccessful . Subjects had a history of peripheral nerve injury or dysfunction , and all complained of symptoms consistent with neuropathic pain . After baseline pain measurements , mexiletine or placebo was given in gradually increasing doses to a maximum daily dose of 750 mg mexiletine . After 1 month at steady state , the subject received the alternative medication . Mexiletine was found to produce a statistically significant reduction in reported pain when compared to baseline or placebo . Pain scores were rated on a scale from 0 ( no pain ) to 10 ( unbearable pain ) . Median pain scores prior to mexiletine were 7 , after placebo treatment 7 , and while receiving mexiletine ( 750 mg/day ) 4 . Side effects were mild and well-tolerated . Mexiletine may be effective in reducing neuropathic pain for patients in whom alternative pain medications have been unsatisfactory Patients with multiple sclerosis ( MS ) often show positive symptoms of painful tonic seizure and dysesthesia as well as negative symptoms of paralysis and hypesthesia . Positive manifestation is paroxysmal and /or persistent . These are considered to be mediated by ectopic impulses generated at the site of demyelination , whereas negative symptoms are caused by conduction block . Conduction block at a demyelinated segment should reduce positive symptoms , but worsen negative ones . As reported previously , lidocaine , an Na channel blocker unmasks silent negative symptoms presumably by further reducing the action current in demyelinated portions and blocking conduction . Furthermore , because it blocks Na channels in a voltage- and frequency dependent manner , fibers that mediate positive symptoms are preferentially blocked . We administered lidocaine to 30 MS patients with positive symptoms . Lidocaine ( mean plasma level , 2.4 pg/ml ) almost completely abolished the paroxysmal manifestation of painful tonic seizures , neuralgic attacks , paroxysmal itching , and Lhermitte 's sign . It also markedly alleviated persistent symptoms , but less so than paroxysmal symptoms . Similar effects were obtained with orally-administered mexiletine ( 300 - 400 mg/day ) , a derivative of lidocaine , but to a lesser extent . Na channel blockers have a dual effect on symptoms in MS , depending on whether symptoms are positive or negative . The mechanism that produces positive symptoms and the effects of the drugs on these symptoms are discussed Background : Neuropathic pain is often severe and resistant to pharmacological treatment . The aims of the present study were to assess the analgesic effect of ketamine and lidocaine and to investigate if measurement of different variables of sensibility could be used to identify responders . We also wanted to study if treatment result ed in changes of sensibility Pain intensity , muscle strength , static muscle endurance , pressure pain threshold , and pain tolerance at tender points and control points were assessed in 31 patients with fibromyalgia ( FM ) , before and after intravenous administration of morphine ( 9 patients ) , lidocaine ( 11 patients ) , and ketamine ( 11 patients ) . The three different studies were double-blind and placebo-controlled . The patients were classified as placebo-responders , responders ( decrease in pain intensity by > 50 % ) and non-responders . The morphine test did not show any significant changes . The lidocaine test showed a pain decrease during and after the infusion . The ketamine test showed a significant reduction in pain intensity during and after the test period . Tenderness at tender points decreased and endurance increased significantly , while muscle strength remained unchanged . The present results support the hypothesis that the NMDA receptors are involved in pain mechanisms in fibromyalgia . These findings also suggest that central sensitization is present in FM and that tender points represent secondary hyperalgesia & NA ; Background : Systemic lidocaine has been reported to be effective in treating several neuropathic pain syndromes . Few reports relate plasma lidocaine concentration to analgesia and the available studies have been complicated by labile plasma lidocaine concentrations . We used a computer‐controlled infusion pump ( CCIP ) to target and maintain stable plasma lidocaine concentrations and study the effect of intravenous lidocaine on ( 1 ) pain scores , ( 2 ) current perception thresholds , ( 3 ) side effects , and ( 4 ) pain distribution in patients suffering from peripheral nerve injury pain . Methods : This study used a r and omized double‐blind placebo‐controlled design . Eleven patients suffering from neuropathic pain after peripheral nerve injury received both a lidocaine and saline infusion in separate study sessions . The order of the study sessions was r and omized and separated from each other by 1 week . The CCIP was programmed to target plasma lidocaine concentrations of 0.5 , 1 , 1.5 , 2 , and 2.5 & mgr;g/ml , each held for 10 min . Pain scores and pain distribution were assessed in the painful area , and electrical current perception thresholds ( CPT ) of the ring finger were measured using a cutaneous perception threshold neurometer ( Neurometer CPT , Neurotron , Baltimore , MD ) . Side effects were recorded at fixed intervals . Plasma lidocaine concentrations were measured at 4 and 9 min after each step increase in infusion and correlated with the observed effects . Results : Saline infusion had no effect . However , with lidocaine there was a significant plasma concentration‐dependent decrease in pain scores starting at 1.5 & mgr;g/ml . This effect typically corresponded with a decrease in the size of the receptive field to which the pain was referred . For the electrical stimulus , there was no significant effect on cutaneous perception at 2000‐Hz stimulation at the highest concentration examined ; however , there was a significant increase in thresholds at 250‐Hz ( starting at 1.5 & mgr;g/ml ) and 5‐Hz ( starting at 1.0 & mgr;g/ml ) stimulation . There were no serious side effects . In all , 54.5 % of patients reported lightheadedness ( average plasma lidocaine concentration : 1.5 & mgr;g/ml ) and one patient reported nausea ( 2.3 & mgr;g/ml ) . Discussion : The computer‐controlled delivery of intravenous lidocaine results in relatively stable plasma concentrations which allows a more thorough evaluation of the relationship between plasma concentration and patient response . This administration methodology for intravenous lidocaine may prove to be a valuable clinical and research tool In a r and omized , double-blind , crossover study , we evaluated the effect of intravenous lidocaine ( 5 mg/kg body weight over 30 min ) on the neuropathic pain of advanced cancer patients . Pain intensity , assessed by a visual analogue scale , did not show any significant difference between lidocaine and placebo infusion . The blinded choice of patients and investigators also suggested no significant improvement from lidocaine when given by this regimen . Intravenous lidocaine does not appear to have a significant analgesic effect on neuropathic cancer pain Background Phantom and stump pains , common sequelae of limb amputations , are significant impediments to rehabilitation of amputees . The pathophysiology and optimal treatment of postamputation pain states are unclear . While stump pain may result from neuromas in the stump , phantom pain is thought to be related to cortical reorganization . The authors hypothesized that morphine and lidocaine may have differential effectiveness on stump and phantom pains . Methods The authors conducted a r and omized double-blind , active-placebo-controlled , crossover trial to compare the analgesic effects of intravenous morphine and lidocaine on postamputation stump and phantom pains . An intravenous bolus followed by an intravenous infusion of morphine ( 0.05 mg/kg bolus + 0.2 mg/kg infusion over 40 min ) , lidocaine ( 1 mg/kg bolus + 4 mg/kg infusion ) and the active placebo , diphenhydramine ( 10 mg bolus + 40 mg infusion ) , were performed on three consecutive days . Phantom and stump pain ratings and sedation scores were recorded at 5-min intervals using a 0–100 visual analog scale . Pain measures were initiated 30 min before drug infusion and continued until 30 min after the end of infusion . Subjects ’ self-reported pain relief and satisfaction were assessed at the end of each infusion . Results Thirty-one of 32 subjects enrolled completed the study . Eleven subjects had both stump and phantom pains , 11 and 9 subjects had stump and phantom pain alone , respectively . Baseline pain scores were similar in the three drug groups . Compared with placebo , morphine reduced both stump and phantom pains significantly ( P < 0.01 ) . In contrast , lidocaine decreased stump ( P < 0.01 ) , but not phantom pain . The changes in sedation scores for morphine and lidocaine were not significantly different from placebo . Compared with placebo , self-reported stump pain relief was significantly greater for lidocaine ( P < 0.05 ) and morphine ( P < 0.01 ) , while phantom pain relief was greater only for morphine ( P < 0.01 ) . Satisfaction scores were significantly higher for lidocaine ( mean ± SD : 39.3 ± 37.8 , P < 0.01 ) and morphine ( 45.9 ± 35.5 , P < 0.01 ) when compared with placebo ( 9.6 ± 21.0 ) . Conclusions Stump pain was diminished both by morphine and lidocaine , while phantom pain was diminished only by morphine , suggesting that the mechanisms and pharmacological sensitivity of stump and phantom pains are different Background : Pre clinical studies have emphasized that persistent small afferent input will induce a state of central facilitation that can be regulated by systemically administered lidocaine . The authors extended these pre clinical studies to human volunteers by examining the concentration‐dependent effects of intravenous lidocaine on acute sensory thresholds and facilitated processing induced by intradermal capsaicin . Methods : Fifteen healthy persons received a lidocaine or a placebo infusion . A computer‐controlled infusion pump targeted sequential stepwise increases in plasma lidocaine concentration steps of 1 , 2 , and 3 micro gram/ml . At each plasma concentration , neurosensory testing ( thermal and von Frey hair test stimulation ) were performed . After completing the tests at the 3 micro gram/ml plasma lidocaine level , intradermal capsaicin was injected into the volar aspect of the left forearm , and the flare response and hyperalgesia to von Frey hair stimulation , stroking , and heat was assessed . Results : The continuous infusion of lidocaine and placebo had no significant effect on any stimulus threshold . Although intravenous lidocaine result ed in a decrease in all secondary hyperalgesia responses , this was only significant for heat hyperalgesia . Intravenous lidocaine result ed in a significant decrease in the flare response induced by intradermal capsaicin . Conclusions : These studies suggest that the facilitated state induced by persistent small afferent input human pain models may predict the activity of agents that affect components of nociceptive processing that are different from those associated with the pain state evoked by “ acute ” thermal or mechanical stimuli . Such insight may be valuable in the efficient development of novel analgesics for both neuropathic and post‐tissue‐injury pain states The occurrence of ventricular premature depolarizations in survivors of myocardial infa rct ion is a risk factor for subsequent sudden death , but whether antiarrhythmic therapy reduces the risk is not known . The Cardiac Arrhythmia Suppression Trial ( CAST ) is evaluating the effect of antiarrhythmic therapy ( encainide , flecainide , or moricizine ) in patients with asymptomatic or mildly symptomatic ventricular arrhythmia ( six or more ventricular premature beats per hour ) after myocardial infa rct ion . As of March 30 , 1989 , 2309 patients had been recruited for the initial drug-titration phase of the study : 1727 ( 75 percent ) had initial suppression of their arrhythmia ( as assessed by Holter recording ) through the use of one of the three study drugs and had been r and omly assigned to receive active drug or placebo . During an average of 10 months of follow-up , the patients treated with active drug had a higher rate of death from arrhythmia than the patients assigned to placebo . Encainide and flecainide accounted for the excess of deaths from arrhythmia and nonfatal cardiac arrests ( 33 of 730 patients taking encainide or flecainide [ 4.5 percent ] ; 9 of 725 taking placebo [ 1.2 percent ] ; relative risk , 3.6 ; 95 percent confidence interval , 1.7 to 8.5 ) . They also accounted for the higher total mortality ( 56 of 730 [ 7.7 percent ] and 22 of 725 [ 3.0 percent ] , respectively ; relative risk , 2.5 ; 95 percent confidence interval , 1.6 to 4.5 ) . Because of these results , the part of the trial involving encainide and flecainide has been discontinued . We conclude that neither encainide nor flecainide should be used in the treatment of patients with asymptomatic or minimally symptomatic ventricular arrhythmia after myocardial infa rct ion , even though these drugs may be effective initially in suppressing ventricular arrhythmia . Whether these results apply to other patients who might be c and i date s for antiarrhythmic therapy is unknown We investigated the analgesic efficacy of mexiletine and gabapentin on acute and chronic pain associated with cancer breast surgery in 75 patients . They were r and omized to receive , in a double-blinded manner , mexiletine 600 mg/d , gabapentin 1200 mg/d , or placebo for 10 days . Anesthesia was st and ardized , and all patients had access to routine postoperative analgesics on dem and . The visual analog scale score assessed pain at rest and after movement . Three months later , all patients were interviewed to identify intensity of chronic pain and analgesic requirements . Mexiletine and gabapentin reduced codeine consumed from the second to tenth day by 50 % ( P = 0.029;P = 0.018 and P = 0.035 for mexiletine versus control and gabapentin versus control comparisons , respectively ) . Total paracetamol consumption was also reduced during the same time ( P = 0.0085;P = 0.007 and P = 0.011 for the mexiletine and gabapentin groups when compared with the control , respectively ) . Pain at rest and after movement was reduced by both drugs on the third postoperative day . Pain after movement also was reduced by gabapentin between the second and fifth postoperative day . Three months later , the incidence of chronic pain , its intensity , and need for analgesics were not affected by either treatment . However , burning pain was more frequent in the control group ( P = 0.033 ) Background : Painful sensory neuropathy is a common complication of HIV infection . Based on prior uncontrolled observations , we hypothesized that amitriptyline or mexiletine would improve the pain symptoms . Method : A r and omized , double-blind , 10-week trial of 145 patients assigned equally to amitriptyline , mexiletine , or matching placebo . The primary outcome measure was the change in pain intensity between baseline and the final visit . Results : The improvement in amitriptyline group ( 0.31 ± 0.31 units [ mean ± SD ] ) and mexiletine group ( 0.23 ± 0.41 ) was not significantly different from placebo ( 0.20 ± 0.30 ) . Both interventions were generally well tolerated . Conclusions : Neither amitriptyline nor mexiletine provide significant pain relief in patients with HIV-associated painful sensory neuropathy & NA ; Tocainide is a derivative of lidocaine with anti‐arrhythmic action and , unlike lidocaine , can be used for oral treatment . Tocainide was alternatively with carbamazepine given to 12 patients with trigeminal neuralgia in a double‐blind cross‐over study for 2 weeks . The analgesic effect was estimated each day by the patients using a 0–10‐point scale summarizing the frequency and severity of the attacks . The similarity in analgesic effect of the two drugs was striking . A possible analgesic mechanism could be that tocainide blocks the sodium channels in the hyperexcitable nerve membranes in the pain‐producing foci in trigeminal neuralgia OBJECTIVE To prove the efficacy of mexiletine in painful diabetic neuropathy . RESEARCH DESIGN AND METHODS Treatment was provided in three dosages . For pain measurements , a VAS and McGill 's verbal rating scale were chosen . Ninety-five patients were included in the study . RESULTS A global assessment of the VAS among patients showed no differences between mexiletine treatment and placebo . The total evaluation ( PRIT ) of the McGill scale fell just below the level of significance . More specific exploratory evaluations of subclasses of the McGill scale , representing different degrees of pain , gave remarkable differences between mexiletine and placebo in sensory and miscellaneous items . In special subgroups , which were formed according to types and courses of complaints compiled at the beginning of this evaluation , the substantial advantages of the mexiletine treatment were shown with both the VAS and the McGill scale . CONCLUSIONS Evidence strongly indicates that , in particular , those patients with stabbing or burning pain , heat sensations , or formication will benefit most by mexiletine therapy . Concerning the dosage , a medium regimen of 450 mg/day seems to be appropriate . With an increase in the antiarryhthmic dosage level , the efficacy does not rise proportionally . Mexiletine proved to be a safe therapy with negligible side effects at the medium dose range , even < placebo ; and remarkably , no cardiovascular side effects were noted . Further studies should avoid global assessment s and pay more attention to the variety of complaints and quality of life |
2,256 | 29,936,326 | HIIT appears to be safe and effective in increasing fitness in people with MS and low levels of disability . | BACKGROUND Aerobic high intensity interval training ( HIIT ) is safe in the general population and more efficient in improving fitness than continuous moderate intensity training .
The body of literature examining HIIT in multiple sclerosis ( MS ) is exp and ing but to date a systematic review has not been conducted .
The aim of this review was to investigate the efficacy and safety of HIIT in people with MS . | Background — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies Introduction Low-to-moderate intensity exercise improves muscle contractile properties and endurance capacity in multiple sclerosis ( MS ) . The impact of high intensity exercise remains unknown . Methods Thirty-four MS patients were r and omized into a sedentary control group ( SED , n = 11 ) and 2 exercise groups that performed 12 weeks of a high intensity interval ( HITR , n = 12 ) or high intensity continuous cardiovascular training ( HCTR , n = 11 ) , both in combination with resistance training . M.vastus lateralis fiber cross sectional area ( CSA ) and proportion , knee-flexor/extensor strength , body composition , maximal endurance capacity and self-reported physical activity levels were assessed before and after 12 weeks . Results Compared to SED , 12 weeks of high intensity exercise increased mean fiber CSA ( HITR : + 21±7 % , HCTR : + 23±5 % ) . Furthermore , fiber type I CSA increased in HCTR ( + 29±6 % ) , whereas type II ( + 23±7 % ) and IIa ( + 23±6 % , ) CSA increased in HITR . Muscle strength improved in HITR and HCTR ( between + 13±7 % and + 45±20 % ) and body fat percentage tended to decrease ( HITR : -3.9±2.0 % and HCTR : -2.5±1.2 % ) . Furthermore , endurance capacity ( Wmax + 21±4 % , time to exhaustion + 24±5 % , VO2max + 17±5 % ) and lean tissue mass ( + 1.4±0.5 % ) only increased in HITR . Finally self-reported physical activity levels increased 73±19 % and 86±27 % in HCTR and HITR , respectively . Conclusion High intensity cardiovascular exercise combined with resistance training was safe , well tolerated and improved muscle contractile characteristics and endurance capacity in MS . Trial Registration Clinical Trials.gov Abstract Purpose A better underst and ing of how people with multiple sclerosis ( pwMS ) recover from exercise may help inform interventions . Methods We explored physiological and perceptual responses following exercise of different intensities , using a crossover exposure-response design , in 14 adults with multiple sclerosis ( MS ) and 9 controls . A cycling exercise test determined maximum capacity ( Wpeak ) . Participants then performed 20-min exercise sessions relative to Wpeak ( r and om order separated by 7 days ) : ( 1 ) 45 % and ( 2 ) 60 % continuous cycling and ( 3 ) 90 % intermittent cycling ( 30 s cycling , 30 s rest ) . During a 45-min recovery period , tympanic temperature ( Temp ° C ) , exertion in breathing ( RPEbr ) and legs ( RPEleg ) , and cortical excitability ( MEParea ) were measured . Results Eleven pwMS and eight controls completed the study . Controls performed better on the exercise test ( p < 0.05 ) , thus more absolute work during subsequent sessions . PwMS took longer to recover RPEleg with recovery time increasing with intensity ( 45%-6 min ; 60%-15 min ; 90%-35 min ) and correlating with Temp ° C . MEParea was significantly depressed in both groups at 45 % and 60 % ( p < 0.001 ) , in the MS group this also correlated with RPEleg . Conclusions Feelings of leg exertion may persist after exercise in some pwMS , especially at high intensities . This may relate to body temperature and , after continuous exercise , cortical excitability . These results support considering the recovery period post exercise and provide an insight into potential correlates of post-exercise fatigue . Implication s for Rehabilitation A better underst and ing of how pwMS recover following exercise may help inform exercise prescription a long side fatigue management . This study showed that , in pwMS , the time taken to recover from feelings of leg fatigue increased with the intensity of the exercise session rather that total work performed and was related to increase in body temperature . The results of this relatively small study support the need to consider a recovery period after exercise and provide an insight into potential physiological Introduction The prevalence of impaired glucose tolerance ( IGT ) is higher in persons with multiple sclerosis ( MS ) compared to healthy controls , indicating metabolic deficits that may increase comorbidity . In other population s , IGT can , at least partly , be reversed by intense physical exercise , but this is never investigated before in MS . Aim To investigate the effect of high intensity aerobic and resistance training on glucose tolerance and skeletal muscle GLUT4 content in MS . Methods Thirty-four persons with MS ( aged 45 ± 3 years , EDSS 2.5 ± 1.07 ) were r and omized into three groups , including a ( 1 ) sedentary control group ( SED , n = 11 ) , ( 2 ) 12-week high intensity interval plus resistance training group ( HITR , n = 12 ) , or ( 3 ) 12-week high intensity continuous aerobic training plus resistance training group ( HCTR , n = 11 ) . Before and after 12 weeks , glucose tolerance and skeletal muscle GLUT4 content were determined by an oral glucose tolerance test and analysis of a m.vastus lateralis biopsy , respectively . Results There were no significant changes for subjects of SED . From pre- to post-intervention , total area under the glucose curve ( tAUC ) decreased significantly in both HITR ( −6.9 ± 6.2 % ) and HCTR ( −11.0 ± 7.7 % ) ( P < 0.05 ) . Insulin tAUC decreased ( −12.3 ± 14.7 % ) within HCTR and muscle GLUT4 content increased ( + 6.6 ± 4.5 % ) in HITR . Conclusion Twelve weeks of high intensity aerobic exercise in combination with resistance training improved glucose tolerance in persons with MS Background Poststroke guidelines recommend moderate-intensity , continuous aerobic training ( MCT ) to improve aerobic capacity and mobility after stroke . High-intensity interval training ( HIT ) has been shown to be more effective than MCT among healthy adults and people with heart disease . However , HIT and MCT have not been compared previously among people with stroke . Objective The purpose of this study was to assess the feasibility and justification for a definitive r and omized controlled trial ( RCT ) comparing HIT and MCT in people with chronic stroke . Design A preliminary RCT was conducted . Setting The study was conducted in a cardiovascular stress laboratory and a rehabilitation research laboratory . Patients Ambulatory people at least 6 months poststroke participated . Intervention Both groups trained 25 minutes , 3 times per week , for 4 weeks . The HIT strategy involved 30-second bursts at maximum-tolerated treadmill speed alternated with 30- to 60-second rest periods . The MCT strategy involved continuous treadmill walking at 45 % to 50 % of heart rate reserve . Measurements Measurements included recruitment and attendance statistics , qualitative HIT acceptability , adverse events , and the following blinded outcome variables : peak oxygen uptake , ventilatory threshold , metabolic cost of gait , fractional utilization , fastest treadmill speed , 10-Meter Walk Test , and Six-Minute Walk Test . Results During the 8-month recruitment period , 26 participants consented to participate . Eighteen participants were enrolled and r and omly assigned to either the HIT group ( n=13 ) or the MCT group ( n=5 ) . Eleven out of the 13 HIT group participants attended all sessions . Participants reported that HIT was acceptable and no serious adverse events occurred . St and ardized effect size estimates between groups were moderate to very large for most outcome measures . Only 30 % of treadmill speed gains in the HIT group translated into overground gait speed improvement . Limitations The study was not design ed to definitively test safety or efficacy . Conclusions Although further protocol optimization is needed to improve overground translation of treadmill gains , a definitive RCT comparing HIT and MCT appears to be feasible and warranted UNLABELLED Poststroke hemiparesis often leads to a vicious cycle of limited activity , deconditioning , and poor cardiovascular health . Accumulating evidence suggests that exercise intensity is a critical factor determining gains in aerobic capacity , cardiovascular protection , and functional recovery after stroke . High-intensity interval training ( HIT ) is a strategy that augments exercise intensity using bursts of concentrated effort alternated with recovery periods . However , there was previously no stroke-specific evidence to guide HIT protocol selection . PURPOSE This study aim ed to compare within-session exercise responses among three different HIT protocol s for persons with chronic ( > 6 months after ) stroke . METHODS Nineteen ambulatory persons with chronic stroke performed three different 1-d HIT sessions in a r and omized order , approximately 1 wk apart . HIT involved repeated 30-s bursts of treadmill walking at maximum tolerated speed , alternated with rest periods . The three HIT protocol s were different on the basis of the length of the rest periods , as follows : 30 s ( P30 ) , 60 s ( P60 ) , or 120 s ( P120 ) . Exercise tolerance , oxygen uptake ( V˙O2 ) , HR , peak treadmill speed , and step count were measured . RESULTS P30 achieved the highest mean V˙O2 , HR , and step count but with reduced exercise tolerance and lower treadmill speed than P60 or P120 ( P30 : 70.9 % V˙O2peak , 76.1 % HR reserve ( HRR ) , 1619 steps , 1.03 m·s(-1 ) ; P60 : 63.3 % V˙O2peak , 63.1 % HRR , 1370 steps , 1.13 m·s(-1 ) ; P120 : 47.5 % V˙O2peak , 46.3 % HRR , 1091 steps , 1.10 m·s(-1 ) ) . P60 achieved treadmill speed and exercise tolerance similar to those in P120 , with higher mean V˙O2 , HR , and step count . CONCLUSIONS For treadmill HIT in chronic stroke , a combination of P30 and P60 may optimize aerobic intensity , treadmill speed , and stepping repetition , potentially leading to greater improvements in aerobic capacity and gait outcomes in future studies 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 . Background : The most effective exercise dose has yet to be established for multiple sclerosis ( MS ) . Objective : The aim of this study was to investigate the effect of different exercise intensities in people with MS . Methods : We completed a r and omized comparator study of three cycling exercise intensities , with blinded assessment , was carried out in Oxford . Sixty-one adults with MS who fulfilled inclusion criteria were r and omized at entry into the study , using a computer-generated list held by an exercise professional , into either : continuous ( at 45 % peak power , n = 20 ) , intermittent ( 30 sec on , 30 sec off at 90 % peak power , n = 21 ) or combined ( 10 min intermittent at 90 % peak power then 10 min continuous at 45 % peak power , n = 20 ) exercise for 20 min twice a week for 12 weeks in a leisure facility . Groups were assessed at : baseline , halfway ( 6 weeks ) , end intervention ( 12 weeks ) and follow-up ( 24 weeks ) . Primary outcome measure was 2 min walk . Results : Fifty-five participants were included in the analysis ( n = continuous 20 , intermittent 18 , combined 17 ) . No differences were found between groups . After 6 weeks , considering all participants , 2 min walk distance increased by 6.96 ± 2.56 m ( 95 % CI : 1.81 to 12.10 , effect size ( es ) : 0.25 , p < 0.01 ) . The continuous group increased by 4.71 ± 4.24 m ( 95 % CI : −3.80 to 13.22 , es : 0.06 ) , intermittent by 12.94 ± 4.71 m ( 95 % CI : 3.97 to 21.92 , es : 0.28 ) and combined by 3.22 ± 4.60 m ( 95 % CI : −6.01 to 12.46 , es : 0.04 ) . Two minute walk did not significantly change between further assessment s. Between 6 and 12 weeks there was a drop in attendance that seemed to be associated with the intermittent and combined groups ; these groups also had a greater number of adverse events ( leg pain during cycling most common ) and dropouts ( n = continuous 1 , intermittent 5 , combined 10 ) . Considering all participants , 6 weeks of cycling exercise produced benefits in mobility that were maintained with further sessions . Conclusion : While no differences were found between groups , greater benefit may be associated with higher-intensity exercise , but this may be less well tolerated . CONSORT - trial registration number ( IS RCT N89009719 OBJECTIVE To compare the immediate effects of different training interventions on gait parameters in patients with early Parkinson 's disease ( PD ) . DESIGN R and omized , multiple intervention crossover pilot study . SETTING A rehabilitation center for adult persons with neurologic disorders . PARTICIPANTS Seventeen patients with early PD ( Hoehn and Yahr stages I through III ) and gait disturbances . INTERVENTION Patients were r and omly assigned to varying sequences of the following interventions over 4 consecutive days : structured speed-dependent treadmill training ( STT ) , limited progressive treadmill training ( LTT ) , conventional gait training ( CGT ) , and a control intervention . MAIN OUTCOME MEASURES Basic gait parameters ( overground walking speed and stride length at self-adapted speeds ) and parameters of gait analysis based on vertical ground reaction forces . RESULTS STT and LTT improved all basic gait parameters and the double stance duration compared with preintervention values ( P<.05 ) . No changes were found after CGT and the control intervention ( P<.05 ) . Significantly higher gains were observed in all basic gait parameters after STT and LTT when compared with CGT and the control intervention ( P<.05 ) . Additionally , a greater reduction of double stance duration was found after STT than after the control intervention ( P<.001 ) . No significant differences in gains were observed between STT and LTT , or between CGT and the control intervention , in all gait parameters . CONCLUSION The main disturbances of gait in PD , namely , speed and stride length , can be improved through a single intervention of STT or LTT , but not through CGT and the control intervention This study tested whether upper-body endurance training ( ET ) is feasible and can be performed at sufficient intensity to induce cardiovascular adaptations in severely disabled patients with progressive multiple sclerosis ( MS ) . Eleven progressive MS patients ( 6.5 ≤ EDSS ≤ 8.0 ) scheduled for a four-week inpatient rehabilitation program were r and omized to a control group ( CON , n = 5 ) that received st and ard individualized MS rehabilitation or an intervention group ( EXE , n = 6 ) that in addition received 10 sessions of predominantly upper-body ET . One patient dropped out of the EXE group ( drop-out rate : 1/6~17 % ) and no adverse events were recorded . The EXE group completed on average 9.3±0.8 sessions ( ~96.0±5 % ) . During the ET sessions an average heart rate of 93.9±9.3beats*min–1 were sustained corresponding to 91.6±6.8 % of the maximal pre-intervention heart rate . In the EXE group a trend toward a time*group interaction was seen for VO2peak ( p = 0.06 ) . ET is feasible in severely disabled patients with progressive MS and it can probably be performed at sufficient intensity to induce cardiovascular adaptations |
2,257 | 24,627,326 | The studies comparing therapeutic ultrasound versus placebo or versus exercise alone did not report on overall satisfaction with treatment , or quality of life .
There was low quality evidence that spinal manipulation reduces pain and functional disability more than ultrasound over the short to medium term .
There is also very low quality evidence that there is no clear benefit on any outcome measure between electrical stimulation and therapeutic ultrasound ; and that phonophoresis results in improved SF-36 scores compared to therapeutic ultrasound .
None of the included studies reported on adverse events related to the application of therapeutic ultrasound .
AUTHORS ' CONCLUSIONS No high quality evidence was found to support the use of ultrasound for improving pain or quality of life in patients with non-specific chronic LBP .
There is some evidence that therapeutic ultrasound has a small effect on improving low-back function in the short term , but this benefit is unlikely to be clinical ly important . | BACKGROUND Chronic non-specific low-back pain ( LBP ) has become one of the main causes of disability in the adult population around the world .
Therapeutic ultrasound is frequently used by physiotherapists in the treatment of LBP and is one of the most widely used electro-physical agents in clinical practice .
OBJECTIVES The objective of this review is to determine the effectiveness of therapeutic ultrasound in the management of chronic non-specific LBP . | BACKGROUND AND OBJECTIVE To develop a checklist of items measuring the quality of reports of r and omized clinical trials ( RCTs ) assessing nonpharmacological treatments ( NPTs ) . STUDY DESIGN AND SETTING The Delphi consensus method was used to select and reduce the number of items in the checklist . A total of 154 individuals were invited to participate : epidemiologists and statisticians involved in the field of methodology of RCTs ( n = 55 ) , members of the Cochrane Collaboration ( n = 41 ) , and clinicians involved in planning NPT clinical trials ( n = 58 ) . Participants ranked on a 10-point Likert scale whether an item should be included in the checklist . RESULTS Fifty-five experts ( 36 % ) participated in the survey . They were experienced in systematic review s ( 68 % were involved in the Cochrane Collaboration ) and in planning RCTs ( 76 % ) . Three rounds of the Delphi method were conducted to achieve consensus . The final checklist contains 10 items and 5 subitems , with items related to the st and ardization of the intervention , care provider influence , and additional measures to minimize the potential bias from lack of blinding of participants , care providers , and outcome assessors . CONCLUSIONS This tool can be used to critically appraise the medical literature , design NPT studies , and assess the quality of trial reports included in systematic review Background Chronic non-specific low-back pain ( LBP ) is one of the most common and expensive musculoskeletal disorders in industrialized countries . Similar to other countries in the world , LBP is a common health and socioeconomic problem in Iran . One of the most widely used modalities in the field of physiotherapy for treating LBP is therapeutic ultrasound . Despite its common use , there is still inconclusive evidence to support its effectiveness in this group of patients . This r and omised trial will evaluate the effectiveness of continuous ultrasound in addition to exercise therapy in patients with chronic LBP . Methods and design A total of 46 patients , between the ages 18 and 65 years old who have had LBP for more than three months will be recruited from university hospitals . Participants will be r and omized to receive continuous ultrasound plus exercise therapy or placebo ultrasound plus exercise therapy . These groups will be treated for 10 sessions during a period of 4 weeks . Primary outcome measures will be functional disability and pain intensity . Lumbar flexion and extension range of motion , as well as changes in electromyography muscle fatigue indices , will be measured as secondary outcomes . All outcome measures will be measured at baseline , after completion of the treatment sessions , and after one month . Discussion The results of this trial will help to provide some evidence regarding the use of continuous ultrasound in chronic LBP patients . This should lead to a more evidence -based approach to clinical decision making regarding the use of ultrasound for LBP.Trial registration Netherl and s Trial Register ( NTR ) : Abstract . The literature on the efficacy of traction in the treatment of low back pain ( LBP ) is conflicting . The aim of this study was to examine its efficacy in this disorder . Forty-two patients with at least 6 weeks of nonspecific LBP were selected . Demographic data were obtained . All patients completed the Oswestry disability index ( ODI ) to assess disability and the 10-cm visual analog scale ( VAS ) for evaluation of pain . Subjects were r and omly assigned into group 1 , receiving only st and ard physical therapy , or group 2 , receiving st and ard physical therapy with conventional lumbar traction . St and ard physical therapy consisted of local heat , ultrasound for the lumbar region , and an active exercise program , given for ten sessions in all . The subjects received instruction on correct posture and recommended therapeutic exercises . They were reevaluated at the end of treatment and at 3-month follow-up . The mean outcome measures were global improvement and satisfaction with the therapy , as well as disability by ODI and pain by VAS . There were no group differences in terms of demographic and baseline clinical characteristics . There was a significant reduction in pain intensity and disability at the end of treatment in both groups . There was complete or mild improvement in 47.6 % of group 1 and 40 % of group 2 . The satisfaction rate with both treatments was more than 70 % immediately after the therapies . During the 3-month period , the outcome measures except disability remained statistically stable , with no difference amongst groups . Disability was significantly reduced at follow-up in both groups . Of the patients , 51 % continued with the recommended exercises and had significantly lower disability scores than those who did not continue with the exercises . Pain and global improvement were also better in this group , but the difference was not statistically significant . In conclusion , no specific effect of traction on st and ard physical therapy was observed in our study group . We suggest focusing on back education and exercise therapy in the management of patients suffering from this chronic condition Our aim is to investigate the effects of three therapeutic approaches in the chronic low back pain on pain , spinal mobility , disability , psychological state , and aerobic capacity . Sixty patients with chronic low back pain were r and omized to three groups : group 1 , aerobic exercise + home exercise ; group 2 , physical therapy ( hot pack , ultrasound , TENS ) + home exercise ; group 3 , home exercise only . Spinal mobility , pain severity , disability , and psychological disturbance of the patients were assessed before and after the treatment and at 1-month follow-up . Aerobic capacities of the patients were measured before and after treatment . All of the groups showed similar decrease in pain after the treatment and at 1-month follow-up , and there was no significant difference between the groups . In group 2 , a significant decrease in Beck Depression Inventory scores was observed with treatment . At 1-month follow-up , group 1 and 2 showed significant decreases in General Health Assessment Question naire scores . In group 2 , there was also a significant improvement in Rol and Morris Disability scores . There were similar improvements in exercise test duration and the MET levels in all the three groups . All of the three therapeutic approaches were found to be effective in diminishing pain and thus increasing aerobic capacity in patients with chronic low back pain . On the other h and , physical therapy + home exercise was found to be more effective regarding disability and psychological disturbance OBJECTIVE --To compare the effectiveness of manipulative therapy , physiotherapy , treatment by the general practitioner , and placebo therapy in patients with persistent non-specific back and neck complaints . DESIGN --R and omised clinical trial . SETTING -- Primary health care in the Netherl and s. PATIENTS --256 patients with non-specific back and neck complaints of at least six weeks ' duration who had not received physiotherapy or manipulative therapy in the past two years . INTERVENTIONS --At the discretion of the manipulative therapists , physiotherapists , and general practitioners . Physiotherapy consisted of exercises , massage , and physical therapy ( heat , electrotherapy , ultrasound , shortwave diathermy ) . Manipulative therapy consisted of manipulation and mobilisation of the spine . Treatment by general practitioners consisted of drugs ( for example , analgesics ) , advice about posture , home exercises , and (bed)rest . Placebo treatment consisted of detuned shortwave diathermy ( 10 minutes ) and detuned ultrasound ( 10 minutes ) . MAIN OUTCOME MEASURES --Changes in severity of the main complaint and limitation of physical functioning measured on 10 point scales by a blinded research assistant and global perceived effect measured on a 6 point scale by the patients . RESULTS --Many patients in the general practitioner and placebo groups received other treatment during follow up . Improvement in the main complaint was larger with manipulative therapy ( 4.5 ) than with physiotherapy ( 3.8 ) after 12 months ' follow up ( difference 0.9 ; 95 % confidence interval 0.1 to 1.7 ) . Manipulative therapy also gave larger improvements in physical functioning ( difference 0.6 ; -0.1 to 1.3 ) . The global perceived effect after six and 12 months ' follow up was similar for both treatments . CONCLUSIONS --Manipulative therapy and physiotherapy are better than general practitioner and placebo treatment . Furthermore , manipulative therapy is slightly better than physiotherapy after 12 months Background Non-specific chronic low back pain ( NSCLBP ) is one of the most common musculoskeletal disorders around the world including Iran . One of the most widely used modalities in the field of physiotherapy is therapeutic ultrasound ( US ) . Despite its common use , there is still inconclusive evidence to support its effectiveness in patients with NSCLBP . The objective of this study was to evaluate the effect of continuous US compared with placebo US additional to exercise therapy for patients with NSCLBP . Methods In this single blind placebo controlled study , 50 patients with NSCLBP were r and omized into two treatment groups : 1 ) continuous US ( 1 MHz & 1.5 W/cm2 ) plus exercise 2 ) placebo US plus exercise . Patients received treatments for 4 weeks , 10 treatment sessions , 3 times per week , every other day . Treatment effects were assessed in terms of primary outcome measures : 1 ) functional disability , measured by Functional Rating Index , and 2 ) global pain , measured by a visual analog scale . Secondary outcome measures were lumbar flexion and extension range of motion ( ROM ) , endurance time and rate of decline in median frequency of electromyography spectrum during a Biering Sorensen test . All outcome variables were measured before , after treatment , and after one-month follow-up . An intention to treat analysis was performed . Main effects of Time and Group as well as their interaction effect on outcome measures were investigated using repeated measure ANOVA . Results Analysis showed that both groups had improved regarding function ( FRI ) and global pain ( VAS ) ( P < .001 ) . Lumbar ROM as well as holding time during the Sorensen test and median frequency slope of all measured paravertebral muscles did not change significantly in either group ( P > .05 ) . Improvement in function and lumbar ROM as well as endurance time were significantly greater in the group receiving continuous US ( P < .05 ) . Conclusions The study showed that adding continuous US to a semi supervised exercise program significantly improved function , lumbar ROM and endurance time . Further studies including a third group of only exercise and no US can establish the possible effects of placebo US.Trial registration Study Design . Multicenter r and omized , controlled trial . Objective . To compare two physical therapy programs for patients with lumbar spinal stenosis . Summary of Background Data . Scant evidence exists regarding effectiveness of nonsurgical management programs for lumbar spinal stenosis . Methods . Fifty-eight patients with lumbar spinal stenosis were r and omized to one of two 6-week physical therapy programs . One program included manual physical therapy , body weight supported treadmill walking , and exercise ( Manual Physical Therapy , Exercise , and Walking Group ) , while the other included lumbar flexion exercises , a treadmill walking program , and subtherapeutic ultrasound ( Flexion Exercise and Walking Group ) . Perceived recovery was assessed with a global rating of change scale . Secondary outcomes included : Oswestry , a numerical pain rating scale , a measure of satisfaction , and a treadmill test . Testing occurred at baseline , 6 weeks , and 1 year . Perceived recovery , pain , and other healthcare re sources used were collected with a long-term follow-up question naire . Results . A greater proportion of patients in the manual physical therapy , exercise , and walking group reported recovery at 6 weeks compared with the flexion exercise and walking group ( P = 0.0015 ) , with a number needed to treat for perceived recovery of 2.6 ( confidence interval , 1.8–7.8 ) . At 1 year , 62 % and 41 % of the manual therapy , exercise , and walking group and the flexion exercise and walking group , respectively , still met the threshold for recovery . Improvements in disability , satisfaction , and treadmill walking tests favored the manual physical therapy , exercise , and walking group at all follow-up points . Conclusions . Patients with lumbar spinal stenosis can benefit from physical therapy . Additional gains may be realized with the inclusion of manual physical therapy interventions , exercise , and a progressive body-weight supported treadmill walking program For ultrasound to be effective , a conducting medium must be placed between the soundhead and the skin . Little research has been performed to test whether or not these mediums actually work . The purpose of this study was to compare the effect of tap water immersion and ultrasound gel conducting mediums on tissue temperature rise in the human leg . A 23-gauge hypodermic needle microprobe was inserted 3 cm deep into the medial portion of the gastrocnemius muscle of 20 subjects . Each subject participated in two r and om order treatments using tap water immersion and topical gel conducting mediums . Each treatment consisted of continuous ultrasound delivered topically at 1.5 W/cm2 for 10 minutes . During both treatments , the soundhead was moved at a speed of 4 cm per second , and the temperature was recorded every 30 seconds . A significant difference was found between the two treatment methods [ t(19 ) = 9.18 , p < .001 ] . The topical gel increased tissue temperature 4.8 degrees C , whereas the underwater treatment increased tissue temperature only 2.1 degrees C. Therefore , at a tissue depth of 3 cm , ultrasound gel is a better conducting medium than water . Also , the authors discovered that it took nearly 8 minutes for the temperature to reach therapeutic levels during the gel technique . These findings should be of clinical significance to clinicians who regularly use ultrasound OBJECTIVES Some occupations are more prone to low back pain ( LBP ) due to their static work postures and work place design . Multidisciplinary pain programs have shown their effectiveness in the management of LBP in general population but which treatment and which segment of the population will be benefited more was not investigated yet . This study determines the effect of two treatment protocol s on five occupationally subgrouped male LBP patients . METHODS A total of 102 occupational male , 20 - 40 yrs of age , with sub-acute or chronic nonspecific LBP were r and omized and treated either with conventional treatment a combination of two electrotherapy ( ultrasound and short wave diathermy ) and one exercise therapy ( lumbar strengthening exercises ) or dynamic muscular stabilization techniques ( DMST ) an active approach of stabilizing training . At the end of the treatment , subjects of both the groups were further stratified in five subgroups on the basis of their occupation . The pain was the primary outcome measure while physical strength [ back pressure changes ( BPC ) and abdominal pressure changes ( APC ) ] the secondary . RESULTS The Pain , BPC and APC of all subgroups improved significantly ( P < 0.01 ) in the both treatments but more in DMST . For each variable , improvement in subgroups differed within and between the treatments . Overall improvement in all assessed variables were evident on Desk workers followed by Shop keepers the most while BPC of Movement job , APC of Others and Pain of Sedentary and Shop keepers improved the least . CONCLUSIONS Study concluded that for the management of occupational LBP , DMST is more effective than conventional treatment . The Pain of Sedentary and Shopkeepers and physical strength of Movement job and Others may need more clinical attention . Findings of this study may be helpful in the management of occupational LBP STUDY DESIGN A descriptive question naire of chartered physiotherapists . OBJECTIVE To investigate current physiotherapeutic management of low back pain throughout Britain and Irel and . SUMMARY OF BACKGROUND DATA Physiotherapists play a key role in low back pain management . Although clinical guidelines for best practice have been developed recently , there has been no large-scale attempt to describe current physiotherapeutic treatment approaches within Britain or Irel and . METHODS After semi-structured interviews ( n = 6 ) and two pilot studies ( n = 77 ) were done , postal question naires were distributed to four regional cluster sample s of the membership of two physiotherapy professional organizations ( n = 2654 ) . After two mailings , a r and om sample of 90 nonresponders were followed up . Data were analyzed using the Statistical Package for the Social Sciences ( SPSS Ltd. , Woking , Surrey , UK ) , and precision of the survey estimates was assessed by calculation of sampling errors and intraclass correlation coefficients for cluster sampling . RESULTS Results were received from 1548 therapists ( total response rate , 58.3 % ) ; of these , 813 reported that they were practicing in setting s in which they treated patients with low back pain . Analysis of the results indicated the overall popularity of the Maitl and mobilization and McKenzie approaches among physiotherapists . Although exercise per se was mentioned frequently by respondents , a marked difference in opinion among therapists regarding the optimal type of exercise for low back pain was obvious . Little evidence was demonstrated of the use of manipulation , fitness programs , or multidisciplinary efforts involving behavioral and physical aspects of treatment . Commonly used methods of electrotherapy were interferential therapy , ultrasound , pulsed short-wave diathermy , and transcutaneous electrical nerve stimulation . CONCLUSIONS The results of this study emphasize the need to evaluate further and improve the dissemination of findings regarding the effectiveness of specific physiotherapy approaches for low back pain management BACKGROUND CONTEXT There have been no trials of optimal chiropractic care in terms of number of office visits for spinal manipulation and other therapeutic modalities . PURPOSE To conduct a pilot study to make preliminary identification of the effects of number of chiropractic treatment visits for manipulation with and without physical modalities ( PM ) on chronic low back pain and disability . STUDY DESIGN / SETTING R and omized controlled trial with a balanced 4x2 factorial design . Conducted in the faculty practice of a chiropractic college outpatient clinic . PATIENT SAMPLE Seventy-two patients with chronic , nonspecific low back pain of mechanical origin . MAIN OUTCOME MEASURES Von Korff pain and disability ( 100-point ) scales . METHODS Patients were r and omly allocated to visits ( 1 , 2 , 3 or 4 visits/week for 3 weeks ) and to treatment regimen ( spinal manipulation only or spinal manipulation with PM ) . All patients received high-velocity low-amplitude spinal manipulation . Half received one or two of the following PM at each visit : soft tissue therapy , hot packs , electrotherapy or ultrasound . RESULTS Pain intensity : At 4 weeks , there was a substantial linear effect of visits favoring a larger number of visits : 5.7 points per 3 visits ( SE=2.3 , p=.014 ) . There was no effect of treatment regimen . At 12 weeks , the data suggested the potential for a similar effect of visits on patients receiving both manipulation and PM . Functional disability : At 4 weeks , a visits effect was noted ( p=.018 ) ; the slope for group means was approximately 5 points per 3 visits . There were no group differences at 12 weeks . CONCLUSIONS There was a positive , clinical ly important effect of the number of chiropractic treatments for chronic low back pain on pain intensity and disability at 4 weeks . Relief was substantial for patients receiving care 3 to 4 times per week for 3 weeks The aim of this trial is to investigate and compare the effects of electrical stimulation ( ES ) program and ultrasound ( US ) therapy on pain , disability , trunk muscle strength , walking performance , spinal mobility , quality of life ( QOL ) , and depression in the patients with chronic low back pain ( CLBP ) . A total of 59 patients with definite CLBP were enrolled in this study . These patients were r and omized into three groups . Group 1 ( n = 20 ) was given an ES program and exercises . Group 2 ( n = 19 ) was given an US treatment and exercises . Group 3 ( n = 20 ) was accepted as the control group and was given only exercises . All of the programs were performed 3 days a week , for 6 weeks . The patients were evaluated according to pain , disability , walking performance , endurance , mobility , QOL , depression . The trunk muscle strength was measured with a h and -held dynamometer . All of the groups showed stastically significant improvements in pain , disability , muscle strength , endurance , walking performance , mobility , sub-scores of SF 36 , and depression when compared with their initial status . The intergroup comparison showed significant difference in physical function , energy and social function sub-groups of SF-36 , VAS pain , extensor muscle strength , between three groups . This difference was statistically significant in the groups 1 and 2 compared to the control group . There was also no significant difference between the groups 1 and 2 . We observed that US treatment and ES treatment were effective in improving pain , isometric extensor muscle strength , and QOL in patients with CLBP Objective Replacement of radiography by sonography for determination of skeletal maturity . Design Sonographic and radiographie evaluation of the maturation of the iliac bone apophysis ( Risser 's sign ) and evaluation of the distal radial epiphyses . Patients 64 children and adolescents with idiopathic scoliosis , aged from 5 to 19 years . Results Sonograms with corresponding radiographs were available for the h and and wrist in 36 cases and for the iliac bone in 28 cases . Comparison of sonographic with radiological data revealed sonography to have a sensitivity for qualifying the status of the distal radial epiphysis of 93.1 % . Specificity was 100 % , accuracy 94.4 % for investigation of the distal radial epiphysis . Overall accuracy for correct determination of Risser 's stage by ultrasound ( in comparison with the radiographie st and ard ) was 89.2 % . Conclusions These findings suggest that ultrasound is a useful and highly acceptable tool for bone age determination in clinical routine or screening studies and will help to reduce ionizing radiation to children and adolescents We r and omly surveyed 100 specialists in rehabilitation medicine and 100 rheumatologists concerning their perceptions of the value of 11 different physical modalities -- cold , active and passive exercise , interferential current , laser , magnetotherapy , microwave , shortwave diathermy , traction , ultrasound and transcutaneous nerve stimulation in the treatment of seven different musculoskeletal conditions -- acute arthritis , joint contracture , neck pain , back pain , tendinitis , reflex sympathetic dystrophy and frozen shoulder . There were significant differences in the perceived benefits of modalities which varied by modality and condition . Overall , rehabilitation medicine specialists regarded modalities to be helpful more often than rheumatologists ( P < 0.001 ) Objective : To assess the effectiveness of therapeutic exercises alone and in combination with a single physical agent — ultrasound — in patients with lumbar spinal stenosis . Design : R and omized , prospect i ve , controlled trial . Setting : Department of Physical Medicine and Rehabilitation , University Hospital . Subjects : Forty-five patients presenting with symptoms of neurological claudication and magnetic resonance image-proven lumbar spinal stenosis were assigned to one of three groups : ultrasound plus exercise group ( group 1 , n = 15 ) , sham ultrasound plus exercise group ( group 2 , n= 15 ) and no exercise — no treatment group ( control group , n = 15 ) . Interventions : Stretching and strengthening exercises for lumbar , abdominal , leg muscles as well as low-intensity cycling exercises were given as therapeutic exercises . Ultrasound was applied with 1 mHz , 1.5 W/cm2 intensity , in continuous mode on the back muscle for 10 minutes in group 1 while ultrasound on/off mode was applied in group 2 . Main outcome measures : Before and after a three-week period , all subjects were evaluated by pain , disability , functional capacity and consumption of analgesic . Results : Thirty-two of the participants were women and 13 were men , with an average age of 53.2 ± 12.68 years ( range 25—82 years ) . After a three-week treatment period , leg pain decreased in group 1 ( —1.47 ± 3.02 ) and group 2 ( —2.47 ± 3.75 ) compared with the control group ( P<0.05 ) . Disability score decreased in group 1 ( —3.94 ± 7.20 ) and group 2 ( —7.80 ± 10.26 ) compared with control group ( P<0.05 ) . We did not find any statistically significant difference between groups 1 and 2 ( P>0.05 ) . The amount of analgesic consumption is significantly less in the group with ultrasound application compared to that in the control group ( P<0.05 ) . Conclusion : The results of our study suggest that therapeutic exercises are effective for pain and disability in patients with lumbar spinal stenosis and that addition of ultrasound to exercise therapy lowers the analgesic intake substantially STUDY DESIGN Counterbalanced , within-subjects experimental design . OBJECTIVE To determine the effect of continuous 1-MHz ultrasound , given at 1.5 W/cm2 and 2.0 W/cm2 for 10 minutes , on tissue temperature in the region of the L4-L5 zygapophyseal joint . BACKGROUND Ultrasound is a modality commonly used for the treatment of lower back pain syndromes . R and omized controlled trials supporting the clinical effectiveness for ultrasound in the treatment of any type of lower back condition are lacking . While one purported purpose of ultrasound is the deep-heating effect , it has not been demonstrated that ultrasound can heat tissues in the area of the lumbar zygapophyseal joints , and the specific parameters needed for a heating effect have not been investigated . To aid in the design of the ultrasound intervention for future r and omized controlled trials , it would be beneficial to have insight into the thermal effects of ultrasound on tissues of the lumbar spine and the parameters needed to produce a thermal effect . The present study examined the heating effect of ultrasound on periarticular tissue in the lumbar spine . METHODS AND MEASURES Continuous , 1-MHz ultrasound at intensities of 1.5 W/cm2 and 2.0 W/cm2 was applied for 10 minutes to the lower back of 6 healthy individuals without lower back pain , while temperature measurements were taken with a hypodermic thermocouple implanted next to the L4-L5 zygapophyseal joint . ANOVA models were used for statistical analysis . RESULTS Statistical analysis confirmed that the 2.0-W/cm2 ultrasound application produced ( a ) a more rapid increase in temperature over time , ( b ) a greater overall level of heating , and ( c ) significantly greater heating 6 minutes after the beginning of ultrasound administration . The mean terminal temperatures ( at 10 minutes ) obtained during the 1.5-W/cm2 and 2.0-W/cm2 ultrasound applications were 38.1 degrees C and 39.3 degrees C , respectively . CONCLUSION Continuous 1-MHz ultrasound given at either 1.5-W/cm2 or 2.0-W/cm2 intensity has the capability of heating lumbar periarticular tissue . The higher-intensity ultrasound result ed in greater and faster temperature increase OBJECTIVE This study measures and compares the outcome of traction , ultrasound , and low-power laser ( LPL ) therapies by using magnetic resonance imaging and clinical parameters in patients presenting with acute leg pain and low back pain caused by lumbar disc herniation ( LDH ) . METHODS A total of 60 patients were enrolled in this study and r and omly assigned into 1 of 3 groups equally according to the therapies applied , either with traction , ultrasound , or LPL . Treatment consisted of 15 sessions over a period of 3 weeks . Magnetic resonance imaging examinations were done before and immediately after the treatment . Physical examination of the lumbar spine , severity of pain , functional disability by Rol and Disability Question naire , and Modified Oswestry Disability Question naire were assessed at baseline , immediately after , and at 1 and 3 months after treatment . RESULTS There were significant reductions in pain and disability scores between baseline and follow-up periods , but there was not a significant difference between the 3 treatment groups at any of the 4 interview times . There were significant reductions of size of the herniated mass on magnetic resonance imaging after treatment , but no differences between groups . CONCLUSIONS This study showed that traction , ultrasound , and LPL therapies were all effective in the treatment of this group of patients with acute LDH . These results suggest that conservative measures such as traction , laser , and ultrasound treatments might have an important role in the treatment of acute LDH OBJECTIVE To study the efficacy of manual therapy and physiotherapy in subgroups of patients with persistent back and neck complaints . The second objective was to determine the correlation between three important outcome measures used in this trial . DESIGN R and omized clinical trial ( subgroup analysis ) . SETTING Primary health care in the Netherl and s. PATIENTS Two hundred fifty-six patients with nonspecific back and neck complaints of at least 6 wk duration who had not received physiotherapy or manual therapy in the past 2 yr . INTERVENTIONS At the discretion of the manual therapists , physiotherapists and general practitioners . Physiotherapy consisted of exercises , massage and physical therapy ( heat , electrotherapy , ultrasound , shortwave diathermy ) . Manual therapy consisted of manipulation and mobilization of the spine . Treatment by the general practitioner consisted of drugs ( e.g. , analgesics ) , advice about posture , home exercises and (bed)rest . Placebo treatment consisted of detuned shortwave diathermy ( 10 min ) and detuned ultrasound ( 10 min ) . MAIN OUTCOME MEASURES Changes in severity of the main complaint and limitation of physical functioning measured on 10-point scales by a blinded research assistant and global perceived effect measured on a 6-point scale by the patients . RESULTS Improvement in the main complaint was larger with manual therapy ( 4.3 ) than with physiotherapy ( 2.5 ) for patients with chronic conditions ( duration complaint of 1 yr or longer ) . Also , improvement in the main complaint was larger with manual therapy ( 5.5 ) than with physiotherapy ( 4.0 ) for patients younger than 40 yr ( both were measured after 12-mo follow-up ) . Labeling of patients by the treating manual therapists as " suitable " or " not suitable " for treatment with manual therapy did not predict differences in outcomes . Generally , there was a moderate to strong correlation between the three outcome measures , although a considerable number of patients gave a relatively low score for perceived benefit , while the research assistant gave a high improvement score for the main complaint and physical functioning . CONCLUSIONS The subgroup analysis suggests better results of manual therapy compared to physiotherapy in chronic patients ( duration of present complaints of 1 yr or longer ) and in patients younger than 40 yr old ) . Differences for other subgroups were less clear . The explorative findings of these subgroup analyses have to be investigated in future research In a r and omized trial , the effectiveness of manual therapy , physiotherapy , continued treatment by the general practitioner , and placebo therapy ( detuned ultrasound and detuned short-wave diathermy ) were compared for patients ( n = 256 ) with nonspecific back and neck complaints lasting for at least 6 weeks . The principle outcome measures were severity of the main complaint , global perceived effect , pain , and functional status . These are presented for 3 , 6 , and 12 weeks follow-up . Both physiotherapy and manual therapy decreased the severity of complaints more and had a higher global perceived effect compared to continued treatment by the general practitioner . Differences in effectiveness between physiotherapy and manual therapy could not be shown . A substantial part of the effect of manual therapy and physiotherapy appeared to be due to nonspecific ( placebo ) effects In this prospect i ve study , 145 patients with lumbar spinal stenosis were evaluated for clinical signs and radiologic findings and conservative treatment results . Clinical parameters such as pain on motion , lumbar range of motion , stralight leg raising test , deep tendon reflexes , dermatomal sensations , motor functions and neurogenic claudication distances ware assessed at admission and were compared after a conservative treatment program was completed . A conservative treatment program consisted of physical therapy ( infrared heating , ultrasonic diathermy and active lumbar exercises ) and salmon calcitonin . Pain on motion ( 100 % ) , restriction of extension ( 77 % ) , limited straight leg raising test ( 23 % ) , neurogenic claudication ( 100 % ) , dermatomal sensory impairment ( 47 % ) , motor deficit ( 29 % ) , and reflex deicit ( 40 % ) were observed in the patients . All aforementioned disturbances except reflex deficits Improved by the conservative treatment and results were statistically significant . The authors conclude that this conservative treatment should be the treatment of choice in elderly patients and in those patients without clinical surgical indications BACKGROUND Low back pain syndromes are one of the most frequent causes of movement limitation in population s of highly industrialized countries . They are listed as the main cause of inability to work among people of working age . Chronic pain and the associated limitation of movement underlie the quest for effective therapies . The use of ultrasound , LLLT , vacuum therapy with Ultra Reiz current in physical therapy of these patients prompts research over their effectiveness in the therapy of patients with low-back pain . The aim of the work was to evaluate the analgesic efficacy of LLLT , ultrasound , and vacuum therapy with Ultra Reiz current in patients with low back pain . MATERIAL AND METHODS The study involved 94 people divided into three groups ( A , B , C ) . Group A ( n=35 ) received a series of 10 low energy laser therapy sessions ( wave length 808 nm , surface density of radiation 510 mW/cm(2 ) , continuous wave form , scanning mode , a dose of 12 J/cm(2 ) on a surface of 100 cm(2 ) [ 10x10 cm ] ) . Patients in Group B ( n=27 ) had ultrasound sessions with a wave intensity of 1 W/cm(2 ) for 3 minutes . Patients in Group C ( n=32 ) underwent vacuum therapy ( 8 kPa ) combined with Ultra Reiz current . Subjective pain assessment was carried out using a modified Latinen question naire and a visual analogue scale of pain intensity . Lumbosacral spine mobility was evaluated with the Schober test and the finger-to- floor test . RESULTS In Group A , following low energy laser therapy , a statistically significant decrease in pain intensity was observed , together with decreased analgesic consumption compared to the other groups . In Group C , following vacuum therapy combined with Ultra Reiz currents , a significant decrease in the frequency of pain was observed together with increased physical activity compared to both Groups A and B , assessed according to a modified Laitinen pain indicator question naire . The biggest improvement in global spine mobility and lumbosacral flexion was observed in Group C ( vacuum therapy plus Ultra Reiz current ) compared to the other groups . However , the most significant improvement in lower spine extension was noted in Group B ( ultrasound ) . CONCLUSIONS 1 . The study showed slightly higher analgesic efficacy of laser biostimulation in comparison to vacuum therapy combined with Ultra Reiz current in patients with low back pain . 2 . A more prominent increase in lumbosacral spine mobility was observed after vacuum therapy combined with Ultra Reiz current and ultrasound therapy Kumar , S , Sharma , VP , and Negi , MPS . Efficacy of dynamic muscular stabilization techniques ( DMST ) over conventional techniques in rehabilitation of chronic low back pain . J Strength Cond Res 23(9 ) : 2651 - 2659 , 2009-Low back pain ( LBP ) is a common health problems . Although it is multifactorial , its treatment varies considerably , including medication , physical therapy modalities , and exercise therapy , and each have several interventions . Despite their effectiveness , their head-to-head comparisons are limited . This study was aim ed at 1 such comparison . A total of 30 hockey players , 18 to 28 years of age , with subacute or chronic LBP were r and omly assigned equally in 2 groups . One group was treated with conventional treatment-a combination of 2 electrotherapies ( ultrasound and short-wave diathermy ) and 1 exercise therapy ( lumbar strengthening exercises)- and the other group was treated with dynamic muscular stabilization techniques ( DMST ) , an active approach of stabilizing training . The results showed that both the treatments are effective in the management of LBP , but DMST was found to be more effective than conventional treatment . The walking , st and ups , climbing , and pain improved 4.7 , 2.0 , 1.4 , and 2.1 times , respectively , more with DMST than with conventional treatment . With time ( days ) , walking , st and ups , climbing , and pain improved ( correlation ) significantly ( p < 0.01 ) higher in DMST ( r = 0.83 to 0.92 ) than in conventional treatment ( r = 0.40 to 0.75 ) , and their rate of improvement ( regression β coefficients ) were also significantly ( p < 0.01 ) higher in DMST ( β = −0.16 to 0.73 ) than in conventional treatment ( β = −0.07 to 0.15 ) . Subjects matching were perfect ( p < 0.01 ) and test-retest reliability of all dependent variables was significantly ( p < 0.01 ) high ( intraclass correlation coefficient ≈ 1 ) . No major adverse effects were recorded in any of the patients in either group . This study concluded that for early recovery , DMST is more suitable than conventional treatment The aim of this trial is to investigate and compare the effects of phonophoresis ( PP ) and ultrasound ( US ) therapy on pain , disability , trunk muscle strength , walking performance , spinal mobility , quality of life ( QOL ) , and depression in the patients with chronic low back pain ( CLBP ) . A total of 60 patients with definite CLBP were included in this study . The patients were r and omized into three groups . Group 1 ( n = 20 ) was accepted as the control group and was given only exercises . Group 2 ( n = 20 ) received US treatment and exercises . Group 3 ( n = 20 ) received PP and exercises . All of the programs were performed 3 days a week , for 6 weeks . The pain ( visual analog scale , VAS ) , disability ( Oswestry Disability Question naire , ODQ and pain disability index , PDI ) , walking performance ( 6 min walking test , 6MWT ) , depression ( Beck Depression Inventory scores , BDI ) , and QOL ( Short Form 36 , SF-36 ) of all participants were evaluated . The trunk muscle strength was measured with a h and held dynamometer . All of the groups showed statistically significant improvements in pain , disability , muscle strength , endurance , 6MWT , mobility , QOL , and depression . The intergroup comparison showed significant differences in VAS pain , 6MWT , and EMS , among three groups . These differences were statistically significant in groups 2 and 3 compared with the group 1 . The intergroup comparison showed significant difference in pain , physical function , and energy subgroups of SF-36 . The differences were statistically in group 3 compared with group 1 and 2 . We observed that US and PP treatments were effective in the treatment of patients with CLBP but PP was not found to be superior over ultrasound therapy OBJECTIVES The purpose of this study was to investigate the effects of electrotherapy and exercise on pain intensity and mobility of connective tissue in patients with myofascial pain syndrome ( MPS ) in their cervical region . METHODS 60 patients were divided into 3 groups using a r and om allocation programme method . A hotpack was applied , and ultrasound was carried out on the patients in the treatment group who were also given exercise training . Exercise training was only given to the exercise group while the control group was given two weeks rest . The demographic characteristics , autonomic symptoms , and other MPS-associated symptoms of patients were recorded . The Short-Form McGill Pain Question naire was used to evaluate the intensity and quality of pain , and a skin-roll test was used to evaluate connective tissue mobility . RESULTS There was a statistically significant difference between treatment and control group on the sensory pain , total pain , and Visual Analog Scale measurements ( p < 0.05 ) . There was a decrease in connective tissue sensitivity measurements in the treatment and control groups . The connective tissue tension measurements were also decreased after treatment in the treatment and exercise groups . CONCLUSION We concluded that combined treatment was more effective to decrease pain intensity , and increase connective tissue mobility PURPOSE We studied the efficacy of osteopathic manual treatment ( OMT ) and ultrasound therapy ( UST ) for chronic low back pain . METHODS A r and omized , double-blind , sham-controlled , 2 × 2 factorial design was used to study OMT and UST for short-term relief of nonspecific chronic low back pain . The 455 patients were r and omized to OMT ( n = 230 ) or sham OMT ( n = 225 ) main effects groups , and to UST ( n = 233 ) or sham UST ( n = 222 ) main effects groups . Six treatment sessions were provided over 8 weeks . Intention-to-treat analysis was performed to measure moderate and substantial improvements in low back pain at week 12 ( 30 % or greater and 50 % or greater pain reductions from baseline , respectively ) . Five secondary outcomes , safety , and treatment adherence were also assessed . RESULTS There was no statistical interaction between OMT and UST . Patients receiving OMT were more likely than patients receiving sham OMT to achieve moderate ( response ratio [ RR ] = 1.38 ; 95 % CI , 1.16 - 1.64 ; P < .001 ) and substantial ( RR = 1.41 , 95 % CI , 1.13 - 1.76 ; P = .002 ) improvements in low back pain at week 12 . These improvements met the Cochrane Back Review Group criterion for a medium effect size . Back-specific functioning , general health , work disability specific to low back pain , safety outcomes , and treatment adherence did not differ between patients receiving OMT and sham OMT . Nevertheless , patients in the OMT group were more likely to be very satisfied with their back care throughout the study ( P < .001 ) . Patients receiving OMT used prescription drugs for low back pain less frequently during the 12 weeks than did patients in the sham OMT group ( use ratio = 0.66 , 95 % CI , 0.43 - 1.00 ; P = .048 ) . Ultrasound therapy was not efficacious . CONCLUSIONS The OMT regimen met or exceeded the Cochrane Back Review Group criterion for a medium effect size in relieving chronic low back pain . It was safe , parsimonious , and well accepted by patients BACKGROUND Although chiropractors often use physical modalities with spinal manipulation , evidence that modalities yield additional benefits over spinal manipulation alone is lacking . OBJECTIVE The purpose of the study was to estimate the net effect of physical modalities on low back pain ( LBP ) outcomes among chiropractic patients in a managed-care setting . METHODS Fifty percent of the 681 patients participating in a clinical trial of LBP treatment strategies were r and omized to chiropractic care with physical modalities ( n = 172 ) or without physical modalities ( n = 169 ) . Subjects were followed for 6 months with assessment s at 2 , 4 , and 6 weeks and at 6 months . The primary outcome variables were average and most severe LBP intensity in the past week , assessed with numerical rating scales ( 0 - 10 ) , and low back-related disability , assessed with the 24-item Rol and -Morris Disability Question naire . RESULTS Almost 60 % of the subjects had baseline LBP episodes of more than 3 months ' duration . The 6-month follow-up was 96 % . The adjusted mean differences between groups in improvements in average and most severe pain and disability were clinical ly insignificant at all follow-up assessment s. Clinical ly relevant improvements in average pain and disability were more likely in the modalities group at 2 and 6 weeks , but this apparent advantage disappeared at 6 months . Perceived treatment effectiveness was greater in the modalities group . CONCLUSIONS Physical modalities used by chiropractors in this managed-care organization did not appear to be effective in the treatment of patients with LBP , although a small short-term benefit for some patients can not be ruled out BACKGROUND Low back pain ( LBP ) is a common musculoskeletal disorder that is highly prevalent in the general population . Management of this pathology includes numerous interventions depending on pain severity : analgesic , nonsteroidal anti-inflammatory drugs , steroid injections . However , the effect size and duration of symptom relief are limited . Physical therapy ( ultrasound [ US ] , laser therapy , manual therapy , interferential current therapy , Back School , aerobic work , therapeutic aquatic exercise acupuncture ) have been reported often with mixed results . AIM To evaluate the short-term effectiveness of high-intensity laser therapy ( HILT ) versus ultrasound ( US ) therapy in the treatment of LBP . DESIGN R and omized clinical trial . SETTING University hospital . POPULATION Thirty patients with LBP were r and omly assigned to a HILT group or a US therapy group . METHODS Study participants received fifteen treatment sessions of HILT or US therapy over a period of three consecutive weeks ( five days/week ) . RESULTS For the 30 study participants there were no between-group differences at baseline in Visual Analogic Scale ( VAS ) and Oswestry Low Back Pain Disability Question naire ( OLBPDQ ) scores . At the end of the 3-week intervention , participants in the HILT group showed a significantly greater decrease in pain ( measured by the VAS ) and an improvement of related disability ( measured by the OLBPDQ ) compared with the group treated with US therapy . CONCLUSION Our findings obtained after 15 treatment sessions with the experimental protocol suggested greater effectiveness of HILT than of US therapy in the treatment of LBP , proposing HILT as a promising new therapeutic option into the rehabilitation of LBP INTRODUCTION A pilot study was conducted to provide an indication of the power density ( PD ) dependent analgesic effect of ultrasound ( US ) under serial application in patients with low back pain . METHODS Thirty patients ( n=3 x 10 ) were r and omly assigned to one of three PDs ( 0.3 , 0.7 or 1.0 W/cm(2 ) ) . Twelve treatments were applied once a day for 2 weeks . The sonation time per treatment was 10 minutes . Patients were unaware of their grouping . Pain intensity ( PI ) was assessed using a visual analogue scale for each treatment . The relationship between the different PI profiles was tested by repeated measures by ANOVA . RESULTS The averaged duration of pain was over 10 years ( chronic low back pain ) . Twenty-seven ( n=3 x 9 ) patients could be analyzed ( three drop-outs ) . In the medium ( 0.7 W/cm(2 ) ) and high ( 1.0 W/cm(2 ) ) PD groups the PI showed a clearly decreasing trend , while in the low ( 0.3 W/cm(2 ) ) PD group , the PI remained stationary . None of the contrasts showed a locally significant effect ( Bonferroni adjustment ) . CONCLUSIONS The observed effect is presumably overestimated . In the low PD group , there were more people out of work , and fewer took analgesic drugs . No conclusive judgement is possible . The concept of the PD-dependent effect of US must be evaluated in trials with greater sample sizes The professional literature contains relatively few r and omized-control studies that have assessed the efficacy of physical therapy approaches to the management of patients with chronic low back pain ( CLBP ) . The purpose s of this study were : 1 ) to investigate the effects of physical agents , joint manipulation , low-tech exercise , and high-tech exercise on objective measures of CLBP ; 2 ) to track the length of CLBP relief ; and 3 ) to determine treatment cost-effectiveness . Two-hundred-fifty subjects ( 68 females , 182 males ; ages 34 - 51 years ) with CLBP following an L5 laminectomy were r and omly assigned into five separate groups for a treatment period of 8 weeks . Chronic low back pain status was measured by modified-modified Schober , Cybex Liftask , and Oswestry procedures . Results revealed that : 1 ) only low-tech and high-tech exercise produced significant improvements ( p < .05 ) in CLBP , 2 ) the mean period of CLBP relief ranged from 1.6 weeks ( control ) to 91.4 weeks ( low-tech exercise ) , and 3 ) low-tech exercise was most cost-effective . It was concluded that : 1 ) low-tech and high-tech exercise were the only effective treatments for CLBP , 2 ) low-tech exercise produced the longest period of CLBP relief , and 3 ) low-tech exercise was the most cost-effective form of treatment . Clinical ly , low-tech exercise may be the treatment method of choice for the effective management of chronic low back pain OBJECTIVE This study determines the efficacy of two such multimodal treatments in the management of lumbar pain syndrome in males and females . METHOD Total subjects of 141 male or female were r and omized to treat either with conventional treatment or by DMST ( dynamic muscular stabilization techniques ) . After stratification on the basis of gender ( 51 male and 21 female ) were found in DMST group whereas ( 40 male and 29 female ) were found in conventional group . The primary outcome measures were pain severity , physical strength ( BPC and APC ) , functional ability ( Walking , Stairs climbing and St and -ups ) and QOL . All patients were assessed at baseline ( day 0 ) , 10 days , 20 days , 90 days and at the end treatment or follow up ( day 180 ) . RESULT In this study the improvement of pain , BPC , APC , Walking , Stair climbing and st and -ups in females and males were 22.5 % and 29.0 % , 60.9 % and 53.7 % , 42.0 % and 51.9 % , 49.8 % and 49.3 % , 54.2 % and 48.7 % , 52.3 % and 39.7 % , higher respectively in DMST as compared to CONV whereas QOL in females of DMST improved by 53.6 % more than the females of CONV while males of DMST improved by 57.9 % more than the males of CONV . CONCLUSION DMST as well as CONV treatments are more effective in males than the females . Study also concluded that subgroup " female " may need more clinical attention during the management of LBP OBJECTIVE To observe the curative effect of different physical rehabilitation techniques on patients with lumbar disc herniation . METHODS Eighty-four patients were r and omly divided into Group A , Group B and Group C. Group A were treated with the computerized pelvis traction and ultrashort wave , Group B were treated with the computerized pelvis traction only , while Groups C were treated with the computerized pelvis traction , the ultrashort wave and the traditional Chinese medicine iontophoresis . The outcome was measured with the Japanese Orthopaedics Association Score ( JOA score ) about lower back pain ( LBP ) . RESULTS Compared with before the treatment , the JOA score of all the 3 groups increase markedly after the treatment ( P<0.001 ) . Compared with group B , the JOA score of Groups A and Group C significantly increased ( P<0.05 ) . Compared with Group A , the JOA score in Group C significantly increased ( P<0.05 ) . CONCLUSION The curative effect of comprehensive rehabilitation on lumbar disc herniation is better than that of the single rehabilitation The purpose was to determine the efficacy of therapeutic ultrasound in patients with chronic low back pain . Thirty-one patients , age 38 - 77 , with low back pain lasting more than three months and the intensity of pain on visual analogue scale at least 50 mm , are r and omly divided in two groups . Ultrasound is applied on the lumbar paravertebral muscle in 16 patients and in 15 patients the machine was not switched on . All patients also underwent kinesitherapy . Pharmacological treatment was not changed during the research ( except the possibility of using paracetamol as the " rescue drug " ) . Following parameters were measured at the beginning and at the end of the research : pain intensity on the visual analogue scale/mm , modified Schober measure/cm , patient 's and physician 's global assessment of treatment efficacy ( 1 - 5 scale ) . The intensity of pain in the ultrasound group before the treatment was 82,7+/-14,0 and after the treatment 79,8+/-12,2 ( p<0,05 ) . The intensity of pain in the placebo group before the treatment was 81,7+/-12,1 and at the end of the treatment 78,9+/-12,1 ( p>0,05 ) . The value of the modified Schober measure for the ultrasound group were 5,7 + 0,8 cm vs. 5,8+/-0,9 cm ( p>0,05 ) and in the placebo group were 5,4+/-0,9 cm vs. 5,6+/-1,0 cm ( p>0,05 ) . There was no significant statistical difference between ultrasound and placebo group regarding the efficacy of the treatment ( patients p>0,05 , physicians p>0,05 ) . Therapeutic ultrasound was effective in decreasing the pain intensity in this research , but showed no improvement regarding the functional ability of the lumbar spine in patients with chronic low back pain Low back pain ( LBP ) is a very common problem in primary care and a major cause of disability . There is no evidence for the efficacy of therapeutic modalities such as ultrasound in LBP In a r and omized , single blind placebo controlled clinical trial , we aim ed to evaluate the effect of continuous ultrasound ( US ) in patients with non specific LBP Of the fifty eight patients recruited , 10 patients ( 8 women and 2 men ) r and omly allocated to ultrasound ( n=5 ) or placebo controlled ( n=5 ) groups . The patients were treated by either US or sham-US for ten sessions , three days per week , every other day . The outcome measures were Functional Rating Index ( FRI ) , Hmax/Mmax ratio and range of motion ( ROM ) , which were measured at baseline , after 5 treatment sessions and at the end of treatment . To analyze the data , The Mann Whitney U test and Wilcoxon Signed Rank test were used . After treatment , both US and placebo groups showed statistically significant decrease in FRI scores indicating improvement in functional ability ( p = 0.042 and p = 0.043 , respectively ) . The mean changes of FRI during the second five treatment sessions and after the end of treatment was significantly better in the US group than in the placebo group ( p = 0.016 and p = 0.032 , respectively ) . Before and after treatment , the mean H reflex latency and Hmax/Mmax ratio , right and left side were similar in the groups ( p > 0.05 ) , and no significant changes were observed in the treatment groups ( p > 0.05 ) . After treatment , the extension and lateral flexion range of motion significantly increased in the US group ( p = 0.04 ) , but the back movements in the placebo group did not show significant changes ( p > 0.05 ) . The present study supports the significant effect of US on LBP , and suggests that US may improve the functional ability of patients with non specific low back pain |
2,258 | 31,955,324 | Quantitative measures of tissue mechanics have the potential to contribute towards more objective diagnosis of hEDS/HSD . | Hypermobile Ehlers-Danlos syndrome ( hEDS ) and hypermobility spectrum disorders ( HSD ) are heritable connective tissue disorders associated with pain , activity limitations and participation restrictions .
A key feature is reported to be reduced stiffness and increased extensibility and elasticity of connective tissues .
Yet diagnosis relies on assessment of joint range of motion , which may be influenced by other factors , and semi-quantitative assessment of forearm skin extensibility .
The objective of this systematic review was to determine if quantitative measures of tissue mechanics can discriminate between hEDS/HSD and healthy tissues . | Objectives : The reproducibility of clinical tests for skin extensibility and consistency , essential for differentiating between types of Ehlers – Danlos syndrome ( EDS ) and benign joint hypermobility syndrome ( BJHS ) , is unknown . Para clinical methods may provide objective differential diagnostic methods . Methods : Six EDS , 11 BJHS , and 19 controls completed the trial . We analysed the overall inter‐examiner agreement on clinical tests for skin extensibility and consistency , in addition to analyses on suction cup ( SC ) and soft tissue stiffness meter ( STSM ) methods . Results : Overall agreement on tests for skin extensibility and consistency varied between 0.44 and 0.72 . Extensibility evaluated by SC showed an insignificant difference between EDS patients and controls ( p = 0.056 ) . Consistency evaluated by STSM showed significant differences ( p = 0.001 ) . Conclusions : Overall inter‐examiner agreement on clinical tests for skin extensibility and consistency was below 0.80 , which was required a priori to conduct a reproducibility study . Further refinement of tests and a training phase are necessary . The SC and STSM results are encouraging but must be reproduced in a larger study population Simple but objective measurement of soft tissue consistency would be advantageous in the assessment of many neurological , lymphostatic and venous disorders . The aim of the present study was to evaluate the feasibility of using a novel h and -held computerized soft tissue stiffness meter ( STSM ) . The STSM describes the soft tissue stiffness ( STS ) in the form of the instantaneous force ( N ) by which the tissue resists the constant deformation produced by a cylindrical intender . Firstly , the STSM was used to test elastomer sample s with known mechanical properties . In the in vivo assessment , 12 healthy , nondisabled adults ( age range , 24 - 57 years ) and 16 subjects with chronic myofascial neck pain syndrome ( age range , 27 - 55 years ) were studied . To study the reproducibility ( coefficient of variation ( CV(% ) ) ) of the method , the measurement sites were either marked with a marker pen ( marked points ) or localized anatomically ( unmarked points ) . Measurements were made from the dorsal forearm ( Arm ) , trapezius ( Tra ) , levator scapulae ( Lev ) , infraspinatus ( Inf ) and deltoideus ( Del ) muscle areas . STS in the forearm was studied during different types of short-term relative isometric loading of the muscle as well as during venous occlusion . STS values of the myofascial trigger points in the Lev muscles were evaluated bilaterally . A linear , positive relationship was found between the indenter force ( N ) and the dynamic compressive modulus ( MPa ) of elastomer stiffness ( r(2 ) = 0.90 , n = 9 ) . Intra- and interrater CVs of marked and unmarked sites varied between 4.31 % and 12.06 % . STS increased linearly along the relative muscle load ( r(2 ) = 0.96 ) and nonlinearly during the venous occlusion ( r(2 ) = 0.97 ) . Statistically significant regional variation of STS was found between the different measurement sites ( p < 0.05 ) . In conclusion , STSM can evaluate tissue stiffness quantitatively and yield reproducible data |
2,259 | 32,303,823 | No significant effects of RWP were seen in diastolic blood pressure or flow-mediated dilation ( FMD ) of the brachial artery .
RWP have the potential to improve vascular health in at risk human population s , particularly in regard to lowering systolic blood pressure ; however , such benefits are not as prevalent as those observed in animal models | Red wine polyphenols ( RWP ) are plant-based molecules that have been extensively studied in relation to their protective effects on vascular health in both animals and humans .
The aim of this review was to quantify and compare the efficacy of RWP and pure resveratrol on outcomes measures of vascular health and function in both animals and humans . | Objectives To determine the incremental net health benefits of dabigatran etexilate 110 mg and 150 mg twice daily and warfarin in patients with non-valvular atrial fibrillation and to estimate the cost effectiveness of dabigatran in the United Kingdom . Design Quantitative benefit-harm and economic analyses using a discrete event simulation model to extrapolate the findings of the RE-LY ( R and omized Evaluation of Long-Term Anticoagulation Therapy ) study to a lifetime horizon . Setting UK National Health Service . Population Cohorts of 50 000 simulated patients at moderate to high risk of stroke with a mean baseline CHADS2 ( Congestive heart failure , Hypertension , Age≥75 years , Diabetes mellitus , previous Stroke/transient ischaemic attack ) score of 2.1 . Main outcome measures Quality adjusted life years ( QALYs ) gained and incremental cost per QALY of dabigatran compared with warfarin . Results Compared with warfarin , low dose and high dose dabigatran were associated with positive incremental net benefits of 0.094 ( 95 % central range −0.083 to 0.267 ) and 0.146 ( −0.029 to 0.322 ) QALYs . Positive incremental net benefits result ed for high dose dabigatran in 94 % of simulations versus warfarin and in 76 % of those versus low dose dabigatran . In the economic analysis , high dose dabigatran dominated the low dose , had an incremental cost effectiveness ratio of £ 23 082 ( € 26 700 ; $ 35 800 ) per QALY gained versus warfarin , and was more cost effective in patients with a baseline CHADS2 score of 3 or above . However , at centres that achieved good control of international normalised ratio , such as those in the UK , dabigatran 150 mg was not cost effective , at £ 42 386 per QALY gained . Conclusions This analysis supports regulatory decisions that dabigatran offers a positive benefit to harm ratio when compared with warfarin . However , no subgroup for which dabigatran 110 mg offered any clinical or economic advantage over 150 mg was identified . High dose dabigatran will be cost effective only for patients at increased risk of stroke or for whom international normalised ratio is likely to be less well controlled Background Synthesis of multiple r and omized controlled trials ( RCTs ) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions . Filtering of search es is time consuming , and no single method fulfills the principal requirements of speed with accuracy . Automation of systematic review s is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making . We developed Rayyan ( http://rayyan.qcri.org ) , a free web and mobile app , that helps expedite the initial screening of abstract s and titles using a process of semi-automation while incorporating a high level of usability . For the beta testing phase , we used two published Cochrane review s in which included studies had been selected manually . Their search es , with 1030 records and 273 records , were uploaded to Rayyan . Different features of Rayyan were tested using these two review s. We also conducted a survey of Rayyan ’s users and collected feedback through a built-in feature . Results Pilot testing of Rayyan focused on usability , accuracy against manual methods , and the added value of the prediction feature . The “ taster ” review ( 273 records ) allowed a quick overview of Rayyan for early comments on usability . The second review ( 1030 records ) required several iterations to identify the previously identified 11 trials . The “ suggestions ” and “ hints , ” based on the “ prediction model , ” appeared as testing progressed beyond five included studies . Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements . The survey respondents reported 40 % average time savings when using Rayyan compared to others tools , with 34 % of the respondents reporting more than 50 % time savings . In addition , around 75 % of the respondents mentioned that screening and labeling studies as well as collaborating on review s to be the two most important features of Rayyan . As of November 2016 , Rayyan users exceed 2000 from over 60 countries conducting hundreds of review s totaling more than 1.6 M citations . Feedback from users , obtained mostly through the app web site and a recent survey , has highlighted the ease in exploration of search es , the time saved , and simplicity in sharing and comparing include-exclude decisions . The strongest features of the app , identified and reported in user feedback , were its ability to help in screening and collaboration as well as the time savings it affords to users . Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of review ers ABSTRACT Endothelial dysfunction is a surrogate marker of cardiovascular risk . Resveratrol is known to improve endothelial function in animals , however , clinical trials are limited . We hypothesized that the acute trans-resveratrol supplementation improves endothelial function in treated hypertensive patients with endothelial dysfunction . Twenty-four hypertensive patients between 45 and 65 years-old with baseline endothelial dysfunction were enrolled in a r and omized , cross-over , double-blind , placebo-controlled trial . Individuals received either a single dose of trans-resveratrol ( 300 mg ) or placebo and were crossed-over after a one-week washout period . Blood pressure ( BP ) measurements , aortic systolic blood pressure ( SBP ) and brachial flow-mediated dilation ( FMD ) were performed before and 1.5 hours after the intervention . FMD was significantly increased in women ( 4.2 ± 0.5 vs 7.1 ± 1.3 % , p = 0.026 ) but not in men ( 4.4 ± 0.9 vs 4.9 ± 0.8 % , p = 0.588 ) in the trans-resveratrol group . There was no statistical difference between baseline and final values of brachial BP and also no changes in aortic SBP . Patients with higher low-density lipoprotein ( LDL ) cholesterol had better FMD response to trans-resveratrol than patients with lower LDL cholesterol ( 7.4 ± 1.2 vs 4.3 ± 1.0 % , p = 0.004 ) . Our study demonstrated that the acute supplementation of trans-resveratrol promoted an improvement in endothelial function , especially in women and those with higher LDL-cholesterol , despite no changes in BP . List of Abbreviation : Aix : augmentation index ; AP : augmentation pressure ; BP : blood pressure ; BMI : body Mass Index ; CVD : cardiovascular disease ; FMD : flow-mediated dilation ; FRS : Framingham Risk Score ; HDL : high-density lipoprotein ; LDL : low-density lipoprotein ; NO : nitric oxide ; SPSS : Statistical Package for Social Sciences ; ROS : reactive oxygen species ; SBP : systolic blood pressure ; TG : triglycerides Abstract Aims Oxidative stress plays a pivotal role in the pathogenesis of type 2 diabetes ( T2D ) . In vitro and animal studies have shown that resveratrol exerts an antioxidant effect , but clinical trials addressing this effect in patients with T2D are limited . The aim of this study was to determine whether resveratrol supplementation affects oxidative stress markers in a r and omized , placebo-controlled , double-blind clinical trial . Methods A total of 48 patients with T2D r and omly were assigned to receive 800 mg/day resveratrol or placebo for 2 months . Plasma total antioxidant capacity , malondialdehyde concentration , protein carbonyl and total thiol contents , intracellular superoxide anion ( O2− · ) and hydrogen peroxide ( H2O2 ) in P BMC s , the expression of genes involved in oxidative stress responses ( Nrf2 , SOD , Cat , HO-1 , RAGE , NOS ) in P BMC s , and metabolic and anthropometric parameters were measured at the baseline and at the trial end . Results Compared with the placebo group , resveratrol reduced plasma protein carbonyl content and P BMC s O2− · level and significantly increased plasma total antioxidant capacity and total thiol content . Furthermore , the expression of Nrf2 and SOD was significantly increased after resveratrol consumption . Resveratrol had no significant effects on the metabolic and anthropometric parameters except for a significant reduction in weight , BMI , and blood pressure levels . Resveratrol was well tolerated , and no serious adverse event was occurred . Conclusions Our study demonstrated that 8 weeks of supplementation with 800 mg/day resveratrol has an antioxidant effect in the blood and P BMC s of patients with T2D . Clinical Trial Registry number and website I RCT registration number : I RCT 2015072523336N1 and http://en . search .i rct .ir/view/24752 Studies on the effects of the long-term intake of trans-resveratrol on vascular function are conflicting . In addition , postpr and ial effects of long-term trans-resveratrol intake on endothelial function are not known . We therefore supplemented 45 overweight and slightly obese volunteers ( 25 men and 20 women ) with a mean ( ±SD ) age of 61 ± 7 years and body mass index of 28.3 ± 3.2 kg/m2 in r and om order trans-resveratrol ( 2 × 75 mg/day ) or placebo capsules for 4 weeks , separated by a washout period of at least 4 weeks . At the end of each intervention period , brachial artery flow-mediated vasodilation ( FMD ) was measured before and after meal consumption . Plasma biomarkers for endothelial function , inflammation , and glucose and lipid metabolism were also determined . Compared with the placebo , trans-resveratrol did not affect fasting FMD ( 2.9 ± 1.4 % vs. 3.0 ± 1.9 % ; p = 0.69 ) . After the postpr and ial test , changes in FMD ( −0.7 ± 2.3 % vs. 0.2 ± 2.6 % ; p = 0.13 ) were also not significantly different . Postpr and ial changes in biomarkers were also comparable . In conclusion , for overweight and slightly obese volunteers , a daily intake of 150 mg of trans-resveratrol for 4 weeks does not change plasma biomarkers of endothelial function or inflammation in the fasting state or postpr and ial phase BACKGROUND The many putative beneficial effects of the polyphenol resveratrol include an ability to bolster endogenous antioxidant defenses , modulate nitric oxide synthesis , and promote vasodilation , which thereby improves blood flow . Resveratrol may therefore modulate aspects of brain function in humans . OBJECTIVE The current study assessed the effects of oral resveratrol on cognitive performance and localized cerebral blood flow variables in healthy human adults . DESIGN In this r and omized , double-blind , placebo-controlled , crossover study , 22 healthy adults received placebo and 2 doses ( 250 and 500 mg ) of trans-resveratrol in counterbalanced order on separate days . After a 45-min resting absorption period , the participants performed a selection of cognitive tasks that activate the frontal cortex for an additional 36 min . Cerebral blood flow and hemodynamics , as indexed by concentration changes in oxygenated and deoxygenated hemoglobin , were assessed in the frontal cortex throughout the posttreatment period with the use of near-infrared spectroscopy . The presence of resveratrol and its conjugates in plasma was confirmed by HPLC after the same doses in a separate cohort ( n = 9 ) . RESULTS Resveratrol administration result ed in dose-dependent increases in cerebral blood flow during task performance , as indexed by total concentrations of hemoglobin . There was also an increase in deoxyhemoglobin after both doses of resveratrol , which suggested enhanced oxygen extraction , that became apparent toward the end of the 45-min absorption phase and was sustained throughout task performance . Cognitive function was not affected . Resveratrol metabolites were present in plasma throughout the cognitive task period . CONCLUSION These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables ABSTRACT Objective “ The obesity epidemic ” has led to an increase in obesity-related conditions including non-alcoholic fatty liver disease ( NAFLD ) , for which effective treatments are in dem and . The polyphenol resveratrol prevents the development of experimental NAFLD through modulation of cellular pathways involved in calorie restriction . We aim ed to test the hypothesis that resveratrol alleviates NAFLD in a r and omised , clinical trial . Material s and methods A total of 28 overweight patients with transaminasemia and histological NAFLD were r and omised 1:1 to placebo or resveratrol 1.5 g daily for 6 months . Twenty-six participants completed the trial and underwent repeated clinical investigation , blood work , MR spectroscopy ; and 19 participants agreed to a repeat liver biopsy . Results Resveratrol treatment was generally not superior to placebo in improving plasma markers of liver injury ( primary outcome : alanine transaminase , p = 0.51 ) . Resveratrol-treated patients showed a 3.8 % decrease in liver lipid content ( p = 0.03 ) , with no difference between the two treatment arms ( p = 0.38 ) and no improvement of histological features . Resveratrol treatment was not associated with improvements in insulin sensitivity or markers of the metabolic syndrome , except for a transient decrease in systolic BP . Microarray analysis and qRT-PCR revealed no major changes in expression profile . Also , we report a serious adverse event in a patient who developed fever and bicytopenia . Conclusions In this placebo-controlled , high-dose and long-term study , resveratrol treatment had no consistent therapeutic effect in alleviating clinical or histological NAFLD , though there may be a small ameliorating effect on liver function tests and liver fat accumulation Grape seed extract ( GSE ) has in vitro antioxidant activity but whether or not it works in vivo is not clear . In a fully r and omised , crossover trial with 4-week treatment periods on 36 men and women with above-average vascular risk , we aim ed to demonstrate that 2 g/day of GSE ( 1 g of polyphenols ) alone , or with 1 g/day of added quercetin in yoghurt , favourably alters vascular function , endothelial function , and degree of oxidative damage in comparison to a control yoghurt . GSE alone improved flow-mediated dilatation determined ultrasonically by an absolute 1.1 % compared with control . There was no effect of the combination of GSE with quercetin . No other blood or urine measure was altered . Thus sufficient polyphenols from GSE appear to be absorbed to influence endothelial nitric oxide production , and GSE has the potential to favourably influence vascular function OBJECTIVE The objective of the study was to evaluate the effects of a grape product rich in dietary fiber and natural antioxidants on cardiovascular disease risk factors . METHODS A r and omized , controlled parallel-group trial was carried out . Thirty-four non-smoking ( 21 normocholesterolemic and 13 hypercholesterolemic ) adults were supplemented for 16 wk with 7.5 g/d of grape antioxidant dietary fiber , a natural product containing 5.25 g of dietary fiber and 1400 mg of polyphenols . Nine non-supplemented non-smokers were followed as a control group . Fasting blood sample s , blood pressure , and anthropometric readings were obtained at baseline and at week 16 . Subjects were allowed to consume their regular diet , which was monitored weekly . RESULTS Grape antioxidant dietary fiber ( 7.5 g/d ) reduced significantly ( P < 0.05 ) total cholesterol ( 9 % ) , low-density lipoprotein cholesterol ( 9 % ) , and systolic and diastolic blood pressures ( 6 % and 5 % respectively ) . Greater reductions in total cholesterol ( 14.2 % ) and low-density lipoprotein cholesterol ( 11.6 % , P < 0.05 ) were observed in hypercholesterolemic subjects . No changes were observed in the control group . There was a reduction of 2.5 points in the Framingham Global Risk Score in the supplemented group . A significant reduction in triacylglycerol concentration took place in the supplemented hypercholesterolemic subjects ( 18.6 % , P < 0.05 ) . CONCLUSION Grape antioxidant dietary fiber showed significant reducing effects in lipid profile and blood pressure . The effects appear to be higher than the ones caused by other dietary fibers , such as oat fiber or psyllium , probably due to the combined effect of dietary fiber and antioxidants Ageing is thought to be associated with decreased vascular function partly due to oxidative stress . Resveratrol is a polyphenol , which in animal studies has been shown to decrease atherosclerosis , and improve cardiovascular health and physical capacity , in part through its effects on Sirtuin 1 signalling and through an improved antioxidant capacity . We tested the hypothesis that resveratrol supplementation enhances training-induced improvements in cardiovascular health parameters in aged men . Twenty-seven healthy physically inactive aged men ( age : 65 ± 1 years ; body mass index : 25.4 ± 0.7 kg m(-2 ) ; mean arterial pressure ( MAP ) : 95.8 ± 2.2 mmHg ; maximal oxygen uptake : 2488 ± 72 ml O2 min(-1 ) ) were r and omized into 8 weeks of either daily intake of either 250 mg trans-resveratrol ( n = 14 ) or of placebo ( n = 13 ) concomitant with high-intensity exercise training . Exercise training led to a 45 % greater ( P < 0.05 ) increase in maximal oxygen uptake in the placebo group than in the resveratrol group and to a decrease in MAP in the placebo group only ( -4.8 ± 1.7 mmHg ; P < 0.05 ) . The interstitial level of vasodilator prostacyclin was lower in the resveratrol than in the placebo group after training ( 980 ± 90 vs. 1174 ± 121 pg ml(-1 ) ; P < 0.02 ) and muscle thromboxane synthase was higher in the resveratrol group after training ( P < 0.05 ) . Resveratrol administration also abolished the positive effects of exercise on low-density lipoprotein , total cholesterol/high-density lipoprotein ratio and triglyceride concentrations in blood ( P < 0.05 ) . Resveratrol did not alter the effect of exercise training on the atherosclerosis marker vascular cell adhesion molecule 1 ( VCAM-1 ) . Sirtuin 1 protein levels were not affected by resveratrol supplementation . These findings indicate that , whereas exercise training effectively improves several cardiovascular health parameters in aged men , concomitant resveratrol supplementation can blunt these effects Resveratrol is a naturally occurring polyphenolic compound . Numerous animal studies have been reported on its wide-ranging beneficial effects in the biological system including diabetes mellitus ( DM ) . We hypothesized , therefore , that oral supplementation of resveratrol would improve the glycemic control and the associated risk factors in patients with type 2 diabetes mellitus ( T2DM ) . The present clinical study was therefore carried out to test the hypothesis . Sixty-two patients with T2DM were enrolled from Government Headquarters Hospital , Ootacamund , India , in a prospect i ve , open-label , r and omized , controlled trial . Patients were r and omized into control and intervention groups . The control group received only oral hypoglycemic agents , whereas the intervention group received resveratrol ( 250 mg/d ) along with their oral hypoglycemic agents for a period of 3 months . Hemoglobin A(1c ) , lipid profile , urea nitrogen , creatinine , and protein were measured at the baseline and at the end of 3 months . The results reveal that supplementation of resveratrol for 3 months significantly improves the mean hemoglobin A(1c ) ( means ± SD , 9.99 ± 1.50 vs 9.65 ± 1.54 ; P < .05 ) , systolic blood pressure ( mean ± SD , 139.71 ± 16.10 vs 127.92 ± 15.37 ; P < .05 ) , total cholesterol ( mean ± SD , 4.70 ± 0.90 vs 4.33 ± 0.76 ; P < .05 ) , and total protein ( mean ± SD , 75.6 ± 4.6 vs 72.3 ± 6.2 ; P < .05 ) in T2DM . No significant changes in body weight and high-density lipoprotein and low-density lipoprotein cholesterols were observed . Oral supplementation of resveratrol is thus found to be effective in improving glycemic control and may possibly provide a potential adjuvant for the treatment and management of diabetes 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 Previous research has shown that resveratrol can increase cerebral blood flow ( CBF ) in the absence of improved cognitive performance in healthy , young human subjects during the performance of cognitively dem and ing tasks . This lack of cognitive effects may be due to low bioavailability and , in turn , reduced bioefficacy of resveratrol in vivo . Piperine can alter polyphenol pharmacokinetics , but previous studies have not investigated whether this affects the efficacy of the target compound . Therefore , the objective of the present study was to ascertain whether co-supplementation of piperine with resveratrol affects the bioavailability and efficacy of resveratrol with regard to cognition and CBF . The present study utilised a r and omised , double-blind , placebo-controlled , within-subjects design , where twenty-three adults were given placebo , trans-resveratrol ( 250 mg ) and trans-resveratrol with 20 mg piperine on separate days at least a week apart . After a 40 min rest/absorption period , the participants performed a selection of cognitive tasks and CBF was assessed throughout the period , in the frontal cortex , using near-IR spectroscopy . The presence of resveratrol and its conjugates in the plasma was confirmed by liquid chromatography-MS analysis carried out following the administration of the same doses in a separate cohort ( n 6 ) . The results indicated that when co-supplemented , piperine and resveratrol significantly augmented CBF during task performance in comparison with placebo and resveratrol alone . Cognitive function , mood and blood pressure were not affected . The plasma concentrations of resveratrol and its metabolites were not significantly different between the treatments , which indicates that co-supplementation of piperine with resveratrol enhances the bioefficacy of resveratrol with regard to CBF effects , but not cognitive performance , and does this without altering bioavailability Resveratrol has been reported to have potent anti-atherosclerotic effects in animal studies . However , there are few interventional studies in human patients with atherosclerogenic diseases . The cardio-ankle vascular index ( CAVI ) reflects arterial stiffness and is a clinical surrogate marker of atherosclerosis . The aim of the present study was to investigate the effect of resveratrol on arterial stiffness assessed by CAVI in patients with type 2 diabetes mellitus (T2DM).In this double-blind , r and omized , placebo-controlled study , 50 patients with T2DM received supplement of a 100 mg resveratrol tablet ( total resveratrol : oligo-stilbene 27.97 mg/100 mg/day ) or placebo daily for 12 weeks . CAVI was assessed at baseline and the end of study . Body weight ( BW ) , blood pressure ( BP ) , glucose and lipid metabolic parameters , and diacron-reactive oxygen metabolites ( d-ROMs ; an oxidative stress marker ) were also measured . Resveratrol supplementation decreased systolic BP ( -5.5 ± 13.0 mmHg ) , d-ROMs ( -25.6 ± 41.8 U.CARR ) , and CAVI ( -0.4 ± 0.7 ) significantly ( P < 0.05 ) and decreased BW ( -0.8 ± 2.1 kg , P = 0.083 ) and body mass index ( -0.5 ± 0.8 kg/m2 , P = 0.092 ) slightly compared to baseline , while there were no significant changes in the placebo group . Decreases in CAVI and d-ROMs were significantly greater in the resveratrol group than in the placebo group . Multivariate logistic regression analysis identified resveratrol supplementation as an independent predictor for a CAVI decrease of more than 0.5.In conclusion , 12-week resveratrol supplementation may improve arterial stiffness and reduce oxidative stress in patients with T2DM . Resveratrol may be beneficial in preventing the development of atherosclerosis induced by diabetes . However , a large-scale cohort study is required to vali date the present findings We tested whether chronic supplementation with resveratrol ( a phytoestrogen ) could improve cerebrovascular function , cognition and mood in post-menopausal women . Eighty post-menopausal women aged 45–85 years were r and omised to take trans-resveratrol or placebo for 14 weeks and the effects on cognitive performance , cerebral blood flow velocity and pulsatility index ( a measure of arterial stiffness ) in the middle cerebral artery ( using transcranial Doppler ultrasound ) , and cerebrovascular responsiveness ( CVR ) to both cognitive testing and hypercapnia were assessed . Mood question naires were also administered . Compared to placebo , resveratrol elicited 17 % increases in CVR to both hypercapnic ( p = 0.010 ) and cognitive stimuli ( p = 0.002 ) . Significant improvements were observed in the performance of cognitive tasks in the domain of verbal memory ( p = 0.041 ) and in overall cognitive performance ( p = 0.020 ) , which correlated with the increase in CVR ( r = 0.327 ; p = 0.048 ) . Mood tended to improve in multiple measures , although not significantly . These results indicate that regular consumption of a modest dose of resveratrol can enhance both cerebrovascular function and cognition in post-menopausal women , potentially reducing their heightened risk of accelerated cognitive decline and offering a promising therapeutic treatment for menopause-related cognitive decline Background : Poor cerebral perfusion may contribute to cognitive impairment in type 2 diabetes mellitus ( T2DM ) . We conducted a r and omized controlled trial to test the hypothesis that resveratrol can enhance cerebral vasodilator function and thereby alleviate the cognitive deficits in T2DM . We have already reported that acute resveratrol consumption improved cerebrovascular responsiveness ( CVR ) to hypercapnia . We now report the effects of resveratrol on neurovascular coupling capacity ( CVR to cognitive stimuli ) , cognitive performance and correlations with plasma resveratrol concentrations . Methods : Thirty-six T2DM adults aged 40–80 years were r and omized to consume single doses of resveratrol ( 0 , 75 , 150 and 300 mg ) at weekly intervals . Transcranial Doppler ultrasound was used to monitor changes in blood flow velocity ( BFV ) during a cognitive test battery . The battery consisted of dual-tasking ( finger tapping with both Trail Making task and Serial Subtraction 3 task ) and a computerized multi-tasking test that required attending to four tasks simultaneously . CVR to cognitive tasks was calculated as the per cent increase in BFV from pre-test basal to peak mean blood flow velocity and also as the area under the curve for BFV . Results : Compared to placebo , 75 mg resveratrol significantly improved neurovascular coupling capacity , which correlated with plasma total resveratrol levels . Enhanced performance on the multi-tasking test battery was also evident following 75 mg and 300 mg of resveratrol . Conclusion : a single 75 mg dose of resveratrol was able to improve neurovascular coupling and cognitive performance in T2DM . Evaluation of benefits of chronic resveratrol supplementation is now warranted The objective of this study was to examine the effectiveness of resveratrol in lowering blood glucose in the presence of st and ard antidiabetic treatment in patients with type 2 diabetes , in a r and omized placebo-controlled double-blinded parallel clinical trial . A total of 66 subjects with type 2 diabetes were enrolled in this study and r and omly assigned to intervention group which was supplemented with resveratrol at a dose 1 g/day for 45 days and control group which received placebo tablets . Body weight , blood pressure , fasting blood glucose , haemoglobin A1c , insulin , homeostatic assessment s for insulin resistance , triglycerides , total cholesterol , low density lipoprotein , high density lipoprotein , and markers of liver and kidney damage were measured at baseline and after 45 days of resveratrol or placebo supplementation . Resveratrol treatment significantly decreased systolic blood pressure , fasting blood glucose , haemoglobin A1c , insulin , and insulin resistance , while HDL was significantly increased , when compared to their baseline levels . On the other h and , the placebo group had slightly increased fasting glucose and LDL when compared to their baseline levels . Liver and kidney function markers were unchanged in the intervention group . Overall , this study showed that resveratrol supplementation exerted strong antidiabetic effects in patients with type 2 diabetes The polyphenol resveratrol is considered to exert many beneficial actions , such as antioxidant , anti-inflammatory , insulin-sensitizer and anticancer effects . Its benefits in patients with type 2 diabetes mellitus ( T2DM ) are controversial . Our aims were to determine whether resveratrol supplementation at two different dosages ( 500 and 40mg/day ) for 6 months i ) reduced the concentrations of C-reactive-protein ( CRP ) and ii ) ameliorated the metabolic pattern of T2DM patients . In the present double-blind , r and omized , placebo-controlled trial , 192 T2DM patients were r and omized to receive resveratrol 500mg/day ( Resv500arm ) , resveratrol 40mg/day ( Resv40arm ) or placebo for 6-months . At baseline and at the trial end , CRP values , anthropometric , metabolic and liver parameters were determined . No serious adverse event occurred . A dose-dependent , though not significant , CRP decrease of 5.6 % ( Resv40arm ) and 15.9 % ( Resv500arm ) was observed vs placebo . We failed to detect significant differences in weight , BMI , waist circumference , and values of arterial blood pressure , fasting glucose , glycated hemoglobin , insulin , C-peptide , free fatty acids , liver transaminases , uric acid , adiponectin , interleukin-6 , in both the Resv500 and Resv40 arms vs placebo . Total cholesterol and triglycerides slightly increased in the Resv500arm . Subgroup analyses revealed that lower diabetes duration ( in both Resv500 and Resv40arms ) , and , in the Resv500arm , younger age , aspirin use and being a smoker were associated with a significantly higher CRP reduction vs placebo . The supplementations with 40mg/day or 500mg/day resveratrol did neither reduce CRP concentrations , nor improve the metabolic pattern of T2DM patients Abstract Consumption of polyphenol-rich food and food ingredient such as grape and grape products improved various cardiovascular parameters . In this study , we investigate the effect of dietary daily consumption of red grape cell powder ( RGC ) on blood pressure ( BP ) and flow-mediated dilatation ( FMD ) as well as on oxidative stress in 50 subjects with prehypertension and mild hypertension . The subjects were r and omized into groups that consumed 200 , 400 mg RGC or placebo daily for 12 weeks . RGC consumption was associated with an improvement of FMD ( p = 0.013 ) . There was a significant decrease in lipid peroxidation ( p = 0.013 ) after 12 weeks in a combined RGC-treated group . The diastolic BP decreased significantly in the 200 mg RGC group compared to the placebo group ( p = 0.032 ) . Our results indicate that a daily supplementation , of red grape cell powder , for 12 weeks affects endothelial function , diastolic BP and oxidative stress without any adverse effects Context Hypertension is a recognized risk factor for the development of congestive heart failure ( CHF ) . By measuring blood pressure , however , we have not yet been able to underst and the significance of pulse pressure as a contributor to CHF in middle-aged men and women . Contribution Using data from the Framingham Heart Study , the authors found that although elevations of systolic , diastolic , and pulse pressure were all related to the risk for CHF , the relation was strongest for systolic and pulse pressure . Caution s Underst and ing the relationships between systolic , diastolic , and pulse pressure and risk for CHF is helpful ; however , they do not help determine the increased risk faced by a person with systolic hypertension who also has increased pulse pressure . The Editors Hypertension is the most common risk factor for congestive heart failure ( CHF ) . It confers a twofold risk for the occurrence of CHF and also carries the highest population attributable risk among all risk factors for CHF ( 1 , 2 ) . Placebo-controlled clinical trials in patients with hypertension have demonstrated a consistent reduction in risk for CHF attributable to the lowering of elevated blood pressure ( 3 - 6 ) . The causal role of hypertension in the pathogenesis of CHF underscores the need to identify high-risk patients because early treatment may prevent or delay the occurrence of CHF ( 2 , 7 ) . The prognostic significance of systolic and diastolic blood pressure in CHF has been reported . However , blood pressure may also be divided into two other components : steady ( mean arterial pressure ) and pulsatile ( pulse arterial pressure ) ( 8 - 10 ) . Pulse pressure , a simple correlate of conduit vessel stiffness , is associated with left ventricular hypertrophy ( 11 ) . Increased pulse pressure has also been implicated in the development and progression of large-vessel atherosclerosis and small-vessel disease ( 12 - 14 ) . Accumulating evidence indicates that pulse pressure ( defined as the difference between systolic and diastolic blood pressure ) may be an important predictor of cardiovascular events ( 15 - 18 ) . Pulse pressure predicts the risk for CHF in elderly persons ( 19 , 20 ) ; however , the association of pulse pressure with CHF in middle-aged men and women has not been examined . The Framingham Heart Study provides an opportunity to examine the long-term associations of systolic , diastolic , and pulse pressure with the new onset of CHF in middle-aged and elderly men and women . Blood pressure and traditional risk factors have been measured repeatedly at serial examinations in this community-based cohort with long-term follow-up . We examined systolic blood pressure , diastolic blood pressure , and pulse pressure as predictors of risk for CHF in the Framingham Heart Study . Methods The Framingham Heart Study , which began in 1948 , has followed 5209 participants ( 28 to 62 years of age at entry to the study ) as part of a prospect i ve epidemiologic study of cardiovascular disease . Enrollment criteria and study design have been published previously ( 21 ) . Biennial follow-up visits included a medical history , physical examination , blood pressure measurements , 12-lead electrocardiography , and laboratory tests . Eligibility requirements for inclusion in our study were as follows : Participants had to be free of coronary heart disease and CHF and not be receiving antihypertensive therapy at Framingham Heart Study clinic baseline examinations 10 , 11 , or 12 ( 1968 to 1973 ) . Participants were followed for onset of CHF through mid-1994 . We obtained data for selected risk factors from the baseline examination . Methods for assessing risk factors have been published previously ( 21 , 22 ) . Risk factors , including age , sex , cigarette smoking , heart rate , antihypertensive medication use , and total and high-density lipoprotein cholesterol levels , were assessed . Sitting systolic and diastolic blood pressure were measured twice by the examining physician ( using a mercury column sphygmomanometer ) and averaged . We used body mass index ( kg/m2 ) as a measure of obesity . Participants were categorized as smokers if they smoked cigarettes regularly within the 1-year period before the baseline examination . Electrocardiography revealed left ventricular hypertrophy when increased voltage was associated with major ST-T repolarization changes ( strain pattern ) ( 22 ) . Diabetes mellitus was defined on the basis of a fasting blood glucose level greater than 7.77 mmol/L ( > 140 mg/dL ) , two r and om nonfasting blood glucose levels greater than 11.10 mmol/L ( > 200 mg/dL ) , or the use of insulin or an oral hypoglycemic agent . Diagnostic criteria for CHF have been described previously ( 21 , 22 ) . At each clinic examination , a history of interim hospitalizations and symptoms of CHF were obtained . Outside medical records of participants who did not attend an examination were evaluated for incident CHF . All suspected interim events were review ed by a panel of three physicians who evaluated relevant Framingham Heart Study clinic notes , outside physician reports , and hospitalization records . Congestive heart failure was diagnosed when at least two major or one major and two minor criteria were present . Minor criteria were considered only if their presence could not be attributed to another disease process . Major criteria were paroxysmal nocturnal dyspnea , pulmonary rales , distended jugular veins , enlarging heart size on chest radiography , acute pulmonary edema , hepatojugular reflux , third heart sound , jugular venous pressure of 16 cm or greater , and weight loss of 4.5 kg or greater in response to diuresis . Major criteria also included pulmonary edema , visceral congestion , or cardiomegaly on autopsy . Minor criteria were bilateral ankle edema , nocturnal cough , shortness of breath on ordinary exertion , hepatomegaly , pleural effusion , decrease in vital capacity by one third from the previous maximum recorded value , and heart rate of 120 beats/min or more . Statistical Analysis We used multivariable Cox proportional-hazards regression models to examine the relations of systolic , diastolic , and pulse pressure with CHF . After accounting for age and sex and using a P value less than 0.15 as the selection criterion , we determined covariates by stepwise selection from the following list : body mass index , diabetes , smoking status , total cholesterol level , high-density lipoprotein ( HDL ) cholesterol level , totalHDL cholesterol ratio , left ventricular hypertrophy , and heart rate . Only total cholesterol level and totalHDL cholesterol ratio did not enter the model . After accounting for relevant covariates , we used Cox proportional-hazards models to obtain hazard ratio estimates with 95 % CIs for st and ardized values of systolic , diastolic , and pulse pressure . These estimates were obtained individually and pairwise by using SAS software ( SAS Institute , Inc. , Cary , North Carolina ) ( 23 ) . We repeated analyses for participants stratified according to hypertension status and sex . Because blood pressure and age are correlated , we conducted separate analyses for participants younger than 60 years of age and 60 years of age and older . To examine constancy of effects over time , follow-up was divided into early and late periods ( < 10 years , 10 years ) , and hazard ratios were calculated separately for early and late follow-up . In addition , we analyzed blood pressure as a time-varying covariate and assessed the effect of antihypertensive treatment after the baseline blood pressure measurements . We used the KaplanMeier method to plot age- and sex-st and ardized cumulative incidence rates for CHF as a function of pulse pressure tertile at baseline . Descriptive data are presented as percentages or means ( SD ) . A P value less than 0.05 was considered statistically significant . Role of the Funding Sources The funding sources had no role in the design , conduct , analyses , and reporting of the study or in the decision to su bmi t the manuscript for publication . Results A total of 894 men and 1146 women , age 50 to 79 years , fulfilled criteria for inclusion in our study . Table 1 presents baseline clinical characteristics for these persons . During 35 497 person-years of follow-up ( mean , 17.4 years [ range , 0.06 to 24 years ] ) , CHF developed in 234 ( 11.8 % ) persons . Myocardial infa rct ion preceded CHF in 59 ( 25 % ) persons . Table 1 . Baseline Clinical Characteristics of the Study Participants Increments of 1 SD in systolic pressure , pulse pressure , and diastolic pressure were associated with hazard ratios for congestive failure of 1.56 , 1.55 , and 1.24 , respectively , after adjustment for age , sex , smoking , left ventricular hypertrophy , body mass index , diabetes mellitus , HDL cholesterol level , and heart rate ( Table 2 ) . When blood pressure tertiles were used , similar associations were observed among various components of blood pressure and CHF . No threshold effect or J-shaped association was documented ( Table 2 ) . The cumulative incidence of CHF according to tertiles of baseline pulse pressure is plotted in the Figure . Table 2 . Risk FactorAdjusted Association of Blood Pressure with Congestive Heart Failure Figure . Cumulative incidence of congestive heart failure according to pulse pressure tertiles at the baseline examination . The joint influences of different blood pressure components were also examined , with adjustment for the covariates mentioned previously . Of note , correlations among the blood pressure variables ranged from modest to very high ( r = 0.20 for diastolic and pulse pressure , r = 0.65 for diastolic and systolic pressure , and r = 0.88 for systolic and pulse pressure ) . Diastolic pressure was not significant ( hazard ratio , 1.12 [ CI , 0.98 to 1.29 ] ) in conjunction with pulse pressure ( hazard ratio , 1.51 [ CI , 1.33 to 1.72 ] ) . Likewise , diastolic pressure was not significant ( hazard ratio , 0.86 [ CI , 0.72 to 1.03 ] ) in conjunction with systolic pressure ( hazard ratio , 1.71 [ CI , 1.45 to 2.01 ] ) , but joint estimates were less stable than those obtained for individual pressure variables . Finally OBJECTIVE Smokers are characterized by a low- grade systemic inflammatory state and an oxidant-antioxidant imbalance . Few human studies were conducted on the effects of resveratrol , a natural compound with anti-inflammatory and antioxidant properties , and no trial on smokers has been performed to date . We evaluated whether resveratrol has beneficial effects on markers of inflammation and oxidative stress in smokers . METHODS AND RESULTS A r and omized , double- blind , cross-over trial was performed in 50 healthy adult smokers : 25 were r and omly allocated to " resveratrol-first " ( 30-days : 500 mg resveratrol/day , 30-days wash-out , 30-days placebo ) and 25 to " placebo-first " ( 30-days placebo , 30-days wash-out , 30-days 500 mg resveratrol/day ) . Resveratrol significantly reduced C-reactive protein ( CRP ) and triglyceride concentrations , and increased Total Antioxidant Status ( TAS ) values . After analyzing data with general linear models to assess period and carry-over effects , the ratios of the values after resveratrol to those after placebo were respectively : 0.47 ( 95%CI 0.38 - 0.59 ) -CRP- and 0.71 ( 95%CI 0.65 - 0.78 ) -triglycerides- , while TAS increased by 74.2 μmol/L ( 95%CI 60.8 - 87.6 ) . Uric acid , glucose , insulin , cholesterol , liver enzyme concentrations , and weight , waist circumference , and blood pressure values did not significantly change after resveratrol supplementation . CONCLUSIONS Because resveratrol has anti-inflammatory , anti-oxidant , and hypotriglyceridemic effects , its supplementation may beneficially affect the increased cardiovascular risk of healthy smokers Polyphenols in grape and wine have been suggested to contribute to the cardiovascular health benefits of the Mediterranean lifestyle . The reported effects of grape products on blood pressure ( BP ) remain , however , equivocal . In a double-blind placebo controlled crossover study , the effect of two grape extracts on BP and vascular function was assessed in 60 untreated , mildly hypertensive subjects after four weeks intervention . Both extracts ( grape-red wine and grape alone ) had high concentrations of anthocyanins and flavonols , but the grape alone was relatively poor in catechins and procyanidins . Parameters measured included ambulatory and office BP , flow-mediated vasodilation , arterial distensibility , platelet function and plasma lipoproteins . Results showed that 24-hour ambulatory systolic/diastolic BPs were significantly lower in the grape-wine extract intervention ( 135.9 ± 1.3/84.7 ± 0.8 mmHg ; mean ± SEM ) compared to placebo ( 138.9 ± 1.3/86.6 ± 1.2 mmHg ) , predominantly during daytime . Plasma concentrations of the vasoconstrictor endothelin-1 decreased by 10 % , but other measures of vascular function were not affected . Grape juice extract alone had no effect on BP or any measures of vascular function . Polyphenol-rich food products , and may be specifically catechins and procyanidins , may thus help sustain a healthy BP and contribute to the healthy Mediterranean lifestyle OBJECTIVE To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of st and ard diabetes care . RESEARCH DESIGN AND METHODS Seventeen subjects with well-controlled type 2 diabetes ( T2D ) were treated with placebo and 150 mg/day resveratrol ( resVida ) in a r and omized double-blind crossover study for 30 days . The main outcome measure was insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique . RESULTS Hepatic and peripheral insulin sensitivity were not affected by resveratrol treatment . Intrahepatic lipid content also remained unaffected by resveratrol ; however , the change in intrahepatic lipid content correlated negatively with plasma resveratrol levels ( R = −0.68 , P = 0.03 ) . Intramyocellular lipid content increased in type 2 muscle fibers ( P = 0.03 ) , and systolic blood pressure tended to decrease ( P = 0.09 ) upon resveratrol treatment . In addition , resveratrol significantly improved ex vivo mitochondrial function ( state 3 and state U respiration upon malate with octanoyl-carnitine , P < 0.005 ) . Intriguingly , a correlation was found between plasma levels of a metabolite of resveratrol ( dihydroresveratrol ) and the metformin dose used by the patients ( R = 0.66 , P = 0.005 ) , suggesting an interaction between metformin and resveratrol . It could be speculated that the lack of a resveratrol-induced insulin-sensitizing effect is caused by this interaction . CONCLUSIONS Resveratrol supplementation does not improve hepatic or peripheral insulin sensitivity . Our results question the generalized value of resveratrol as an add-on therapy in the treatment of T2D and emphasize the need to perform studies in drug-naive patients with T2D or subjects with prediabetes Non-alcoholic fatty liver disease ( NAFLD ) is usually associated with insulin resistance , central obesity , reduced glucose tolerance , type 2 diabetes mellitus and hypertriacylglycerolaemia . The beneficial effects of resveratrol on metabolic disorders have been shown previously . The aim of this study was to evaluate the effects of resveratrol supplementation on cardiovascular risk factors in patients with NAFLD . In this r and omised double-blinded placebo-controlled clinical trial , fifty NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks . Both groups were advised to follow an energy-balanced diet and physical activity recommendations . resveratrol supplementation reduced alanine aminotransferase ( ALT ) and hepatic steatosis significantly more than placebo ( P0·05 ) . There were no significant changes in blood pressure , insulin resistance markers and TAG in either group ( P>0·05 ) . Our data have shown that 12-week supplementation of 500 mg resveratrol does not have any beneficial effect on anthropometric measurements , insulin resistance markers , lipid profile and blood pressure ; however , it reduced ALT and hepatic steatosis in patients with NAFLD Single doses of resveratrol have previously been shown to increase cerebral blood flow ( CBF ) with no clear effect on cognitive function or mood in healthy adults . Chronic resveratrol consumption may increase the poor bioavailability of resveratrol or otherwise potentiate its psychological effects . In this r and omised , double-blind , placebo-controlled , parallel-groups study , a total of sixty adults aged between 18 and 30 years received either placebo or resveratrol for 28 d. On the 1st and 28th day of treatment , the performance of cognitively dem and ing tasks ( serial subtractions , rapid visual information processing and 3-Back ) ( n 41 complete data sets ) was assessed , alongside blood pressure ( n 26 ) and acute ( near-IR spectroscopy ( NIRS ) ) and chronic ( transcranial Doppler ) measures of CBF ( n 46 ) . Subjective mood , sleep quality and health question naires were completed at weekly intervals ( n 53/54 ) . The results showed that the cognitive effects of resveratrol on day 1 were restricted to more accurate but slower serial subtraction task performance . The only cognitive finding on day 28 was a beneficial effect of resveratrol on the accuracy of the 3-Back task before treatment consumption . Subjective ratings of ' fatigue ' were significantly lower across the entire 28 d in the resveratrol condition . Resveratrol also result ed in modulation of CBF parameters on day 1 , as assessed by NIRS , and significantly increased diastolic blood pressure on day 28 . Levels of resveratrol metabolites were significantly higher both before and after the day 's treatment on day 28 , in comparison with day 1 . These results confirm the acute CBF effects of resveratrol and the lack of interpretable cognitive effects BACKGROUND AND AIMS Flow-mediated dilatation of the brachial artery ( FMD ) is a biomarker of endothelial function and cardiovascular health . Impaired FMD is associated with several cardiovascular risk factors including hypertension and obesity . Various food ingredients such as polyphenols have been shown to improve FMD . We investigated whether consuming resveratrol , a polyphenol found in red wine , can enhance FMD acutely and whether there is a dose-response relationship for this effect . METHODS AND RESULTS 19 overweight/obese ( BMI 25 - 35 kg m(-2 ) ) men or post-menopausal women with untreated borderline hypertension ( systolic BP : 130 - 160 mmHg or diastolic BP : 85 - 100 mmHg ) consumed three doses of resveratrol ( resVida ™ 30 , 90 and 270 mg ) and a placebo at weekly intervals in a double-blind , r and omized crossover comparison . One hour after consumption of the supplement , plasma resveratrol and FMD were measured . Data were analyzed by linear regression versus log(10 ) dose of resveratrol . 14 men and 5 women ( age 55 ± 2 years , BMI 28.7 ± 0.5 kg m(-2 ) , BP 141 ± 2/89 ± 1 mmHg ) completed this study . There was a significant dose effect of resveratrol on plasma resveratrol concentration ( P < 0.001 ) and on FMD ( P < 0.01 ) , which increased from 4.1 ± 0.8 % ( placebo ) to 7.7 ± 1.5 % after 270 mg resveratrol . FMD was also linearly related to log(10 ) plasma resveratrol concentration ( P < 0.01 ) . CONCLUSION Acute resveratrol consumption increased plasma resveratrol concentrations and FMD in a dose-related manner . This effect may contribute to the purported cardiovascular health benefits of grapes and red wine Diabetes-induced CVD is the most significant complication of prolonged hyperglycaemia . The aim of this study was to determine whether resveratrol , a polyphenol antioxidant compound , when administered at a dose that can be reasonably obtained through supplementation could prevent the development of cardiovascular complications in older , obese , diabetic rats . Diabetes was induced in 6-month old , obese , male Wistar rats via a single intravenous dose of streptozotocin ( 65 mg/kg ) . R and omly selected animals were administered resveratrol ( 2 mg/kg ) via oral gavage daily for 8 weeks . Body weights , blood glucose levels , food intake and water consumption were monitored , and assessment s of vascular reactivity , tactile allodynia and left ventricular function were performed . Resveratrol therapy significantly improved tactile allodynia and vascular contractile functionality in diabetic rats ( P<0·05 ) . There were no significant changes in st and ardised vasorelaxation responses , plasma glucose concentrations , water consumption , body weight , left ventricular hypertrophy , kidney hypertrophy , heart rate or left ventricular compliance with resveratrol administration . Resveratrol-mediated improvements in vascular and nerve function in old , obese , diabetic rats were associated with its reported antioxidant effects . Resveratrol did not improve cardiac function nor mitigate the classic clinical symptoms of diabetes mellitus ( i.e. hyperglycaemia , polydypsia and a failure to thrive ) . This suggests that supplementation with resveratrol at a dose achievable with commercially available supplements would not produce significant cardioprotective effects in people with diabetes mellitus Objective : To examine the hypothesis that resveratrol administration could result in blood pressure and blood flow decrease in a rat preeclampsia model . Material s and Methods : Desoxycorticosterone acetate ( DOCA ) was used to produce hypertension . The Wistar albino rats were divided r and omly into three groups : control ( n = 12 ) , DOCA injected ( n = 11 ) , and DOCA injected and resveratrol treated ( n = 13 ) . Rats were sacrificed on gestational day 16–20 . The systolic blood pressure was measured by the tail-cuff method . Urine protein was expressed as protein/creatinine . Laser Doppler measurements of the blood flow were made in one placenta , the left kidney and both parietal lobes of brain . Placentas were examined by light microscopy . Results : DOCA injected group exhibited significant differences in blood pressure and protein/creatinine . Mean blood pressure in DOCA-treated rats was 130.1 ± 12.9 mmHg at baseline and 148.4 ± 20.1 mmHg at the time of euthanization ( p = 0.044 ) . Resveratrol did not significantly affect blood pressure , placental and renal blood flows . There were also no significant differences in placental pathology parameters among the three groups . Conclusion : The present study demonstrated that resveratrol did not decrease blood pressure , and did not result in a significant response in blood flows and placental pathology parameters Data suggest that polyphenol-rich products may improve endothelial function and other cardiovascular health risk factors . Grape and wine contain high amounts of polyphenols , but effects of these polyphenols have hardly been investigated in isolation in r and omized controlled studies . Our objective in this study was to test the chronic effect of polyphenol-rich solids derived from either a wine grape mix or grape seed on flow-mediated dilation ( FMD ) . Blood pressure and other vascular function measures , platelet function , and blood lipids were secondary outcomes . Thirty-five healthy males were r and omized in a double-blind , placebo-controlled crossover study consisting of three 2-wk intervention periods separated by 1-wk washout periods . The test products , containing 800 mg of polyphenols , were consumed as capsules . At the end of each intervention period , effects were measured after consumption of a low-fat breakfast ( ~751 kJ , 25 % fat ) and a high-fat lunch ( ~3136 kJ , 78 % fat ) . After the low-fat breakfast , the treatments did not significantly affect FMD . The absolute difference after the wine grape solid treatment was -0.4 % ( 95 % CI = -1.8 to 0.9 ; P = 0.77 ) and after grape seed solids , 0.2 % ( 95 % CI = -1.2 to 1.5 ; P = 0.94 ) compared with after the placebo treatment . FMD effects after the high-fat lunch and effects on secondary outcomes also showed no consistent differences between both of the grape solids and placebo treatment . In conclusion , consumption of grape polyphenols has no major impact on FMD in healthy men . Future studies should address whether grape polyphenols can improve FMD and other cardiovascular health risk factors in population s with increased cardiovascular risk Dietary polyphenols , such as those from grape products , may exert beneficial effects on cardiovascular health , including anti-hypertensive effects . We investigated the effect of a specific grape seed extract ( GSE ) rich in low-molecular-weight polyphenolic compounds on ambulatory blood pressure ( ABP ) in untreated subjects with pre- and stage I hypertension . In addition , potential mechanisms that could underlie the hypothesised effect of GSE on blood pressure ( BP ) , and platelet aggregation , were explored . The study was design ed as a double-blind , placebo-controlled , r and omised , parallel-group intervention study including seventy healthy subjects with systolic BP between 120 and 159 mmHg . A 1-week run-in period was followed by an 8-week intervention period , during which subjects consumed capsules containing either 300 mg/d of GSE or a placebo ( microcrystalline cellulose ) . Before and after the intervention , daytime ABP readings , 24 h urine sample s and fasting and non-fasting blood sample s were taken . The mean baseline systolic BP was 135.8 ( SE 1.3 ) mmHg and diastolic BP was 81.5 ( SE 0.9 ) mmHg . BP values were modestly , but not significantly , affected by the polyphenol-rich GSE treatment v. placebo with an effect of - 3.0 mmHg for systolic BP ( 95 % CI - 6.5 , 0.5 ) and - 1.4 mmHg for diastolic BP ( 95 % CI - 3.5 , 0.6 ) . Vasoactive markers including endothelin-1 , NO metabolites and asymmetric dimethylarginine , plasma renin activity and platelet aggregation were not affected by the GSE intervention . Our findings show that consumption of polyphenol-rich GSE does not significantly lower ABP in untreated subjects with pre- and stage I hypertension Background : Muscadine grape seeds have high concentrations of polyphenolic compounds with antioxidant and other properties that would be expected to have favorable effects on endothelial function . Objectives : To evaluate the effect of muscadine grape seed supplementation on endothelial function and cardiovascular risk factors in subjects with increased cardiovascular risk . Design : In a r and omized , double-blind , placebo-controlled crossover trial , 50 adults with coronary disease or ≥1 cardiac risk factor received muscadine grape seed supplementation ( 1300 mg daily ) and placebo for 4 weeks each , with a 4-week washout . Resting brachial diameter and brachial flow-mediated dilation ( FMD ) and biomarkers of inflammation , lipid peroxidation , and antioxidant capacity were determined at the beginning and end of each period and compared in mixed linear models . Results : There was no evidence of improved FMD ( % change ) with muscadine grape seed ( muscadine grape seed : pre 5.2 % ± 0.3 % , post 4.6 % ± 0.3 % , p = 0.06 ; placebo : pre 5.3 % ± 0.4 % , post 5.2 % ± 0.4 % , p = 0.82 ; p for muscadine grape seed vs. placebo = 0.25 ) . However , there was a significant increase in baseline diameter ( mm ) with muscadine grape seed supplementation ( muscadine grape seed : pre 4.05 ± 0.09 , post 4.23 ± 0.10 , p = 0.002 ; placebo : pre 4.12 ± 0.11 , post 4.12 ± 0.10 , p = 0.93 ; p for muscadine grape seed vs. placebo = 0.026 ) . All other biomarkers were not significantly altered by muscadine grape seed supplementation . Conclusions : Four weeks of muscadine grape seed supplementation in subjects with increased cardiovascular risk did not produce a statistically significant increase in brachial flow-mediated vasodilation or a significant change in other biomarkers of inflammation , lipid peroxidation , or antioxidant capacity . However , the muscadine grape seed supplement did result in a significant increase in resting brachial diameter . The clinical significance of the effect on resting diameter is not yet established . More research is warranted to fully characterize the vascular effects of this and other grape-derived nutritional supplements and to determine whether these vascular effects translate into important clinical benefits Numerous studies have shown that resveratrol ( RES ) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited . Furthermore , the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood . Therefore , the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells ( P BMC s ) associated to the one-year daily intake of a RES enriched ( 8 mg ) grape extract ( GE-RES ) in hypertensive male patients with type 2 diabetes mellitus ( T2DM ) . We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs ( miRs ) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES . We also examined the changes in several serobiochemical variables , inflammatory and fibrinolytic markers . Our results showed that supplementation with GE or GE-RES did not affect body weight , blood pressure , glucose , HbA1c or lipids , beyond the values regulated by gold st and ard medication in these patients . We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels . The expression of the pro-inflammatory cytokines CCL3 , IL-1β and TNF-α was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in P BMC s from patients taking the GE-RES extract . Also , a group of miRs involved in the regulation of the inflammatory response : miR-21 , miR-181b , miR-663 , miR-30c2 , miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months . Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients We hypothesized that resveratrol , a natural phytoalexin found in grapes , can prevent oxidative stress , obesity and its related disturbances in obese rats programmed by early weaning . Lactating Wistar rats were separated into two groups : early weaning ( EW ) - dams who were wrapped with a b and age to interrupt the lactation in the last 3 days of lactation ; control - dams whose pups had free access to milk during all lactation . At the 150th day , EW offspring were r and omly subdivided into EW+resveratrol ( EW+Res ) - resveratrol ( 30 mg/kg/day ) ; EW+vehicle ( EW ) - rats that received 0.5 % ( w/v ) aqueous methylcellulose . The control group received vehicle . Rats were treated by gavage daily for 30 days . EW offspring developed hyperphagia , higher body weight , visceral obesity , higher systolic ( SBP ) and diastolic blood pressure ( DBP ) ( + 15 % and + 20 % , respectively ; P<.05 ) and higher serum triglycerides ( TG ) and low-density lipoprotein but lower high-density lipoprotein ( + 55 % , + 33 % and -13 % , respectively ; P<.05 ) . Resveratrol normalized food intake , SBP and DBP and prevented obesity and dyslipidemia in EW+Res . EW rats had higher plasma and liver thiobarbituric-acid-reactive substances ( TBARS ) and lower plasma superoxide dismutase ( SOD ) and liver glutathione peroxidase activities ( + 51 % , + 18 % , -58 % , -31 % , respectively ; P<.05 ) , and resveratrol normalized both plasma and liver TBARS and increased the activity of SOD and catalase in plasma . EW rats presented liver steatosis and higher liver TG , and resveratrol prevented these hepatic alterations . In conclusion , this study demonstrated a potential therapeutic use of resveratrol in preventing obesity and oxidative stress and reducing the risk of hypertension , dyslipidemia and steatosis in adult rats programmed by early weaning Objective This study aims to assess the effects of proanthocyanidin — a class of polyphenol antioxidants extracted from grape seeds — on menopausal symptoms , body composition , and cardiovascular parameters in middle-aged women . Methods We conducted a r and omized , double-blind , placebo-controlled study in 96 women aged 40 to 60 years who had at least one menopausal symptom . The study participants were r and omized to receive grape seed extract tablets containing either low-dose ( 100 mg/d ) or high-dose ( 200 mg/d ) proanthocyanidin , or placebo , for 8 weeks . Their menopausal symptoms were evaluated using the Menopausal Health – Related Quality of Life Question naire , Hospital Anxiety and Depression Scale , and Athens Insomnia Scale before and after 4 and 8 weeks of treatment . Body composition and cardiovascular parameters were also measured . Results A total of 91 women ( 95 % ) completed the study . Background characteristics , including age , menopause status , subjective symptom scores , body composition , and cardiovascular parameters , were similar among the groups . The following significant changes were observed during the course of the study : ( 1 ) physical symptom score , hot flash score , and ( 2 ) Athens Insomnia Scale score decreased in the high-dose group after 8 weeks of treatment ; ( 3 ) Hospital Anxiety and Depression Scale Anxiety score and ( 4 ) systolic and diastolic blood pressure decreased in the low-dose and high-dose groups after 4 weeks ; and , ( 5 ) lastly , muscle mass increased in the low-dose and high-dose groups after 8 weeks of treatment . Conclusions Grape seed proanthocyanidin extract is effective in improving the physical and psychological symptoms of menopause while increasing muscle mass and reducing blood pressure in middle-aged women Background : We have previously demonstrated acute dose-dependent increases of flow-mediated dilatation ( FMD ) in the brachial artery after resveratrol consumption in mildly hypertensive , overweight/obese adults . Resveratrol supplementation has also been shown to increase cerebral blood flow acutely , without affecting cognition . Objectives : To evaluate the effects of chronic resveratrol supplementation on both FMD and cognitive performance . Method : Twenty-eight obese but otherwise healthy adults ( BMI : 33.3 ± 0.6 kg/m2 ) were r and omized to take a single 75 mg capsule of trans-resveratrol ( Resvida ) or placebo daily for 6 weeks each in a double-blind crossover supplementation trial . Blood pressure , arterial compliance , FMD , and performance on the Stroop Color-Word Test were assessed at the end of each 6-week intervention period while fasted and at least 18 h after taking the last daily capsule . An additional capsule of the same supplement was then taken . FMD assessment was repeated 1 h later . Results : Chronic resveratrol supplementation for 6 weeks was well tolerated and result ed in a 23 % increase in FMD compared with placebo ( P = 0.021 , paired t-test ) . The extent of increase correlated negatively with baseline FMD ( r = −0.47 , P = 0.01 ) . A single dose of resveratrol ( 75 mg ) following chronic resveratrol supplementation result ed in a 35 % greater acute FMD response than the equivalent placebo supplementation . These FMD improvements remained significant after adjusting for baseline FMD . Blood pressure , arterial compliance , and all components of the Stroop Color-Word Test were unaffected by chronic resveratrol supplementation . Conclusion : Daily resveratrol consumption was well tolerated and has the potential to maintain healthy circulatory function in obese adults Chronic low- grade inflammation is the hallmark of type 2 diabetes ( T2D ) . Although in vitro and animal studies have shown that resveratrol exerts anti-inflammatory effects , clinical trials addressing these effects in patients with T2D are limited . Therefore , in the present study , we hypothesized that supplementation of resveratrol might improve inflammatory markers in patients with T2D in a r and omized , double-blind , placebo-controlled clinical trial . A total of 45 T2D patients were supplemented with either of 800 mg/d resveratrol or placebo capsules for 8 weeks . Percentage of CD14+CD16 + monocytes , plasma levels of inflammatory cytokines ( tumor necrosis factor α , interleukin [ IL ] 1β , IL-6 , and monocyte chemoattractant protein-1 ) , the expression levels of genes involved in the inflammatory responses ( toll-like receptor 2 , toll-like receptor 4 , and nuclear factor κB ) , lipopolysaccharide-stimulated cytokine ( tumor necrosis factor α , IL-1β , and IL-6 ) secretion from peripheral blood mononuclear cells , and metabolic and anthropometric parameters were assessed at both the baseline level and the end of the study . Compared with the placebo group , we could not detect any significant difference in the percentage of CD14+CD16 + monocytes , lipopolysaccharide-induced cytokine secretion , plasma levels of inflammatory cytokines , and the expression of inflammatory genes in resveratrol group . Moreover , we did not find any significant change in the metabolic and anthropometric parameters except for a significant reduction in fasting blood glucose and blood pressure . In conclusion , 8-week supplementation of resveratrol reduces blood glucose level in patients with T2D without improving their inflammatory markers Risk of insulin resistance , impaired glycemic control , and cardiovascular disease is excessive in overweight and obese population s. We hypothesized that increasing expression of glyoxalase 1 (Glo1)—an enzyme that catalyzes the metabolism of reactive metabolite and glycating agent methylglyoxal — may improve metabolic and vascular health . Dietary bioactive compounds were screened for Glo1 inducer activity in a functional reporter assay , hits were confirmed in cell culture , and an optimized Glo1 inducer formulation was evaluated in a r and omized , placebo-controlled crossover clinical trial in 29 overweight and obese subjects . We found trans-resveratrol ( tRES ) and hesperetin ( HESP ) , at concentrations achieved clinical ly , synergized to increase Glo1 expression . In highly overweight subjects ( BMI > 27.5 kg/m2 ) , tRES-HESP coformulation increased expression and activity of Glo1 ( 27 % , P < 0.05 ) and decreased plasma methylglyoxal ( −37 % , P < 0.05 ) and total body methylglyoxal-protein glycation ( −14 % , P < 0.01 ) . It decreased fasting and postpr and ial plasma glucose ( −5 % , P < 0.01 , and −8 % , P < 0.03 , respectively ) , increased oral glucose insulin sensitivity index ( 42 mL ⋅ min−1 ⋅ m−2 , P < 0.02 ) , and improved arterial dilatation Δbrachial artery flow-mediated dilatation/Δdilation response to glyceryl nitrate ( 95 % CI 0.13–2.11 ) . In all subjects , it decreased vascular inflammation marker soluble intercellular adhesion molecule-1 ( −10 % , P < 0.01 ) . In previous clinical evaluations , tRES and HESP individually were ineffective . tRES-HESP coformulation could be a suitable treatment for improved metabolic and vascular health in overweight and obese population |
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6 Kubitza D , Becka M , Wensing G , Voith B , Zuehlsdorf M. Safety , pharmacodynamics , and pharmacokinetics of BAY 59 - 7939 – an oral , direct factor Xa inhibitor – after multiple dosing in healthy male subjects .
8 Graff J , von Hentig N , Misselwitz F , Kubitza D , Becka M , Breddin HK , Harder S. Effects of the oral , direct factor Xa inhibitor rivaroxaban on platelet-induced thrombin generation and prothrombinase activity .
The ecarin time is an improved confirmatory test for the taipan snake venom time in warfarinized patients with lupus anticoagulant . | Background —Numerous studies have suggested that microbial agents may promote atherosclerosis . A smaller body of research has suggested that acute respiratory infection may be a risk factor for myocardial infa rct ion ( MI ) . We hypothesized that influenza vaccine might reduce the risk of recurrent MI in patients with documented coronary heart disease ( CHD ) . Methods and Results —A case-control study was performed on 218 CHD patients seen at Memorial Hermann Hospital during the influenza season of October 1997 through March 1998 . Patients who experienced new MI were included in the case group , and those who did not experience new MI or unstable angina were assigned to the control group . Data were collected by structured review of patients ’ charts and through a subsequent telephone survey . Adjusted for history of influenza vaccination in previous years , multivariate logistic regression revealed risk of MI to be associated with current hypertension ( OR 4.96 , 95 % CI 2.06 to 11.96 , P < 0.0001 ) , hypercholesterolemia ( OR 4.08 , 95 % CI 1.67 to 9.99 , P = 0.002 ) , smoking ( OR 3.75 , 95 % CI 1.76 to 7.98 , P = 0.001 ) , and influenza vaccination ( OR 0.33 , 95 % CI 0.13 to 0.82 , P = 0.017 ) . Despite significant association in univariate analysis , multivitamin therapy and physical exercise were not associated with risk of reinfa rct ion in multivariate analysis . Conclusions —In this study in patients with chronic CHD , vaccination against influenza was negatively associated with the development of new MI during the same influenza season . However , to address causal inference , examination of prospect i ve data sets will be needed We have previously determined that there is a significant benefit of vaccination against influenza in patients hospitalized due to an acute coronary event . The purpose of this study is to determine whether the observed benefits of vaccination were maintained over a 2-year follow-up among those who were re-vaccinated during the subsequent winter season . During the winter season of 2001 , a total of 301 acute coronary patients were prospect ively enrolled within 72 hours of the onset of symptoms . Follow-up was conducted at 6 and 12 months . Patients who survived participated in a registry 1 year after the 2nd influenza vaccination period ( winter 2002 ) , as a cohort of chronic and stable coronary patients . The incidence of the primary endpoint cardiovascular death at 1 year was significantly lower in patients receiving vaccination than in controls ( 6 % vs 17 % , respectively ) by intention-to-treat analysis . The relative risk with vaccination in comparison with controls was 0.34 ; 95 % confidence interval , 0.17 - 0.71 ; P = 0.002 . In the winter of 2002 , 116 patients were vaccinated according to their physicians ' instructions , and 114 subjects remained unvaccinated . The combined endpoints of total death plus myocardial infa rct ion 1 year later were 4 ( 3.4 % ) in the vaccinated group vs 11 ( 9.7 % ) among those who were not vaccinated ( P = 0.05 ) . Influenza vaccination may reduce the risk of death and ischemic events in patients admitted with acute coronary syndromes . There is also a beneficial trend in the quiescent phase of ischemia OBJECTIVES Our objective was to assess endogenous thrombolytic activity in acute coronary syndrome ( ACS ) patients and relate this to their likelihood of future adverse cardiovascular events . BACKGROUND Spontaneous lysis of platelet-rich thrombi is an important defense mechanism against lasting occlusion . Despite convincing evidence for the role of endogenous fibrinolysis in ACS , the prognostic value of plasma fibrinolytic markers in assessing risk is limited . We employed a novel global test which , in addition to platelet reactivity , allows assessment of endogenous thrombolytic activity to identify ACS patients who remain at risk of cardiovascular events . METHODS We used the global thrombosis test ( GTT ) to assess thrombotic and thrombolytic status in 300 ACS patients receiving dual-antiplatelet therapy . The test assesses the time required to form an occlusive thrombus , the occlusion time ( OT ) , and the time to lyse this , the lysis time ( LT ) . The end point of the study at 12 months ' follow-up was the composite of death , nonfatal myocardial infa rct ion , or stroke . RESULTS The OT and LT were both prolonged in ACS patients compared with normal volunteers ( p < 0.001 ) . LT > or = 3,000 s occurred in 23 % of ACS patients versus none of the normal subjects and was a significant and independent predictor of cardiovascular death and nonfatal myocardial infa rct ion in a multivariate model adjusted for cardiovascular risk factors . LT > or = 3,000 s was the optimal cutoff value for predicting 12-month major adverse cardiovascular events ( hazard ratio [ HR ] : 2.52 , 95 % confidence interval : 1.34 to 4.71 , p = 0.004 ) and cardiovascular death ( HR : 4.2 , 95 % confidence interval : 1.13 to 15.62 , p = 0.033 ) . HR increased further as LT increased . No association was found between OT and the risk of major adverse cardiovascular events . CONCLUSIONS Assessment of endogenous thrombolytic status based on the lysis of platelet-rich thrombi from native blood using the point-of-care GTT can identify ACS patients at risk of future cardiac events |
2,261 | 25,931,693 | According to the results of various scales and evaluation instruments , core strength training is more effective than typical resistance training for alleviating chronic low back pain . | [ Purpose ] Through core strength training , patients with chronic low back pain can strengthen their deep trunk muscles .
However , independent training remains challenging , despite the existence of numerous core strength training strategies .
Currently , no st and ardized system has been established analyzing and comparing the results of core strength training and typical resistance training .
Therefore , we conducted a systematic review of the results of previous studies to explore the effectiveness of various core strength training strategies for patients with chronic low back pain . | OBJECTIVE : To contrast the efficacy of two exercise programs , segmental stabilization and strengthening of abdominal and trunk muscles , on pain , functional disability , and activation of the transversus abdominis muscle ( TrA ) , in individuals with chronic low back pain . DESIGN : Our sample consisted of 30 individuals , r and omly assigned to one of two treatment groups : segmental stabilization , where exercises focused on the TrA and lumbar multifidus muscles , and superficial strengthening , where exercises focused on the rectus abdominis , abdominus obliquus internus , abdominus obliquus externus , and erector spinae . Groups were examined to discovere whether the exercises created contrasts regarding pain ( visual analogical scale and McGill pain question naire ) , functional disability ( Oswestry disability question naire ) , and TrA muscle activation capacity ( Pressure Biofeedback Unit = PBU ) . The program lasted 6 weeks , and 30‐minute sessions occurred twice a week . Analysis of variance was used for inter‐ and intra‐group comparisons . The significance level was established at 5 % . RESULTS : As compared to baseline , both treatments were effective in relieving pain and improving disability ( p<0.001 ) . Those in the segmental stabilization group had significant gains for all variables when compared to the ST group ( p<0.001 ) , including TrA activation , where relative gains were 48.3 % and ‐5.1 % , respectively . CONCLUSION : Both techniques lessened pain and reduced disability . Segmental stabilization is superior to superficial strengthening for all variables . Superficial strengthening does not improve TrA activation capacity STUDY DESIGN R and omized clinical trial . OBJECTIVES To determine the efficacy of trunk balance exercises for individuals with chronic low back pain . BACKGROUND The majority of exercises focusing on restoring lumbopelvic stability propose targeting the feedforward control of the lumbopelvic region . Less attention has been paid to feedback control during balance adjustments . METHODS Seventy-nine patients were r and omly allocated to 2 different groups . The experimental group performed trunk balance exercises in addition to st and ard trunk flexibility exercises . The control group performed strengthening exercises in addition to the same st and ard trunk flexibility exercises . The primary outcome measures were pain intensity ( visual analogue scale ) , disability ( Rol and -Morris Question naire ) , and quality of life ( 12-Item Short-Form Health Survey ) . Secondary outcomes were painful positions , use of analgesic drugs , and referred pain . Analysis of variance and relative risk were used to analyze the data for the primary and secondary outcome measures , respectively . The number of participants reaching the minimal clinical ly important difference in the 2 groups for each outcome measure was compared using relative risk . RESULTS A significant difference in scores on the Rol and -Morris Question naire ( P = .011 ) and the physical component of the 12-Item Short-Form Health Survey ( P = .048 ) , and in the number of participants reaching the minimal clinical ly important difference for the Rol and -Morris Question naire ( relative risk , 1.79 ; 95 % confidence interval [ CI ] : 1.05 , 3.04 ) and the secondary outcome of painful positions ( relative risk , 1.37 ; 95 % CI : 1.03 , 1.83 ) were found in favor of the experimental treatment . CONCLUSIONS Trunk balance exercises combined with flexibility exercises were found to be more effective than a combination of strength and flexibility exercises in reducing disability and improving the physical component of quality of life in patients with chronic low back pain [ Purpose ] The purpose of this study was to compare two methods for the muscle stabilization of the trunk of patients with chronic low back pain . The methods comprised combination patterns of proprioceptive neuromuscular facilitation ( PNF ) and ball exercise . [ Subjects and Methods ] The subjects were 40 volunteers who had low back pain . All subjects were r and omly assigned to either a group which received proprioceptive neuromuscular facilitation or a group which performed ball exercise . Measurements were taken four times in total , at pre-intervention , two weeks later , four weeks later , and six weeks later . The main measurement methods used were the visual analogue scale ( VAS ) for pain and electromyography ( EMG ) for muscle activity . [ Results ] VAS and EMG activity were significantly reduced in the PNF combination pattern group and the ball exercise group . A comparison of the groups showed significant differences . In VAS and EMG activity ; in particular , the combination pattern group using PNF increased EMG activity more than the ball exercise group did after six weeks of intervention . [ Conclusion ] This study showed that PNF combination pattern training for six weeks was more effective for patients with low back pain than performing ball exercise Background : Lumbar segmental stability is an important biomechanical component that influences symptoms amongst patients with Mechanical low back pain . Aims : To compare the efficacy of segmental stabilization exercises utilizing multifidus and transversus abdominis muscles versus a placebo treatment in patients with lumbar segmental instability . Material s and methods : The study was an observer-blinded r and omized placebo-controlled cross-over study of 18 adults ( 12 men , 6 women ) , of mean age 22.5 ± 1.09 yrs who scored 7/13 in subjective aspects and 8/14 in objective aspects of Delphi criteria for lumbar segmental instability . The selected subjects were then r and omized to receive either placebo-control ( prone lying ) or experimental ( lumbar segmental stabilization ) as a first treatment . Each treatment was followed by a wash-out period of 24 hours . Outcomes were measured four times- pre- and post- first intervention , pre- and post- second intervention . The outcome measures used were pain on Visual analogue scale , Pressure pain threshold and Joint play grading scale ( 0 - 6 scale ) on that level . Results : Two-way analysis of variance and post-hoc analysis using Bonferonni test were used with level of significance set at p<.05 using Statistical package for social sciences version 12.0.1 for Windows . Visual analogue scale changed significantly in both the periods of intervention- in control ( P = .016 ) and experimental ( P = .000 ) periods . However this improvement was more significant in the experimental period . The Joint play grading scale scores improved only in the experimental condition compared to the control condition significantly . The Pressure pain threshold also improved significantly in the experimental condition ( P = .000 ) while the changes in control condition was not statistically significant ( P=.816 ) . Conclusion : Segmental stabilization exercise was more effective than placebo intervention in symptomatic lumbar segmental instability OBJECTIVE The purpose of this preliminary study was demonstrate if it was feasible to evaluate variations in acceleration of trunk movement , pain , and disability during an episode of acute nonspecific low back pain comparing regular trunk exercises to regular exercises in addition to core stability exercises . METHODS A pilot r and omized controlled trial was used to evaluate 33 participants recruited from a National Health Service physiotherapy musculoskeletal provider in the London district of Hillingdon . Participants were allocated to 2 groups ; a regular exercise group ( male , 2 ; female , 15 ) with a mean ( SD ) age of 35.8 ( 9.1 ) years and intervention group ( male , 3 ; female , 13 ) with a mean ( SD ) age of 36.2 ( 9.8 ) years . The regular exercise group received exercise that consisted of a core stability class including both specific and global trunk exercises . The intervention group , in addition to these core exercises , received further instruction on 8 specific stabilization muscles involving the transversus abdominis and the lumbar multifidus . Trunk sagittal acceleration , pain , and disability were measured using a Lumbar Motion Monitor , pain visual analog scale , and Rol and Morris Disability Question naire , respectively . Measures were taken at baseline , 3 and 6 weeks , and a 3-month follow-up . Multiple regression with adjustment for baseline value was used to analyze each outcome . All outcomes were log transformed to correct skewness and so presented as ratio of geometric means with 95 % confidence interval . RESULTS Differences in mean trunk sagittal acceleration between the regular exercise and intervention groups was not statistically significant at any time point ( ratio of means [ 95 % confidence interval ] : 3 weeks 1.2 [ 0.9 - 1.6 ] , P = .2 ; 6 weeks 1.1 [ 0.8 - 1.5 ] , P = .7 ; 3 months : 1.2 [ 0.8 - 1.9 ] , P = .9 ) . Similarly , the effects on neither pain score nor disability score were significant ( pain score : 3 weeks 1.3 [ 0.8 - 2.2 ] , P = .3 ) ; 6 weeks 1.2 [ 0.7 - 2.0 ] , P = .6 ; 3 months 1.0 [ 0.5 - 1.9 ] , P = 1.0 ) ; disability score : 6 weeks 1.0 [ 0.7 - 1.5 ] , P = 1.0 ; 3 months 1.3 [ 0.8 - 1.9 ] , P = .3 ) . Outcome measures for both groups improved over time . CONCLUSIONS This pilot study demonstrated that a study of this nature is feasible . Both the regular exercise and the intervention groups demonstrated improvements in mean trunk sagittal acceleration at 3 , 6 , and 12 weeks . The preliminary findings showed that evidence was inconclusive for the beneficial effect of adding specific core stability exercises for acute low back pain . The results of this study demonstrated an increase in acceleration accompanied by a reduction in pain , which may suggest that acute nonspecific low back pain may induce the pain-spasm-pain model rather than the pain adaptation model Core training continues to be emphasized with the proposed intent of improving athletic performance . The purpose of this investigation was to discover if core isometric endurance exercises were superior to core isotonic strengthening exercises and if either influenced specific endurance , strength , and performance measures . Ten untrained students were r and omly assigned to core isometric endurance ( n = 5 ) and core isotonic strength training ( n = 5 ) . Each performed three exercises , two times per week for six weeks . A repeated measures ANOVA was used to compare the measurements for the dependent variables and significance by bonferroni post-hoc testing . The training protocol s were compared using a 2 × 3 mixed model ANOVA . Improvement in trunk flexor and extensor endurance ( p < 0.05 ) along with squat and bench press strength ( p < 0.05 ) occurred with the strength group . Improvement in trunk flexor and right lateral endurance ( p < 0.05 ) along with strength in the squat ( p < 0.05 ) were found with the endurance group . Neither training protocol cl aim ed superiority and both were ineffective in improving performance STUDY DESIGN Prospect i ve , single-group , repeated- measures design . OBJECTIVE To identify exercises that could be used for strength development and the exercises that would be more appropriate for endurance or stabilization training . BACKGROUND The exercises analyzed are often used in rehabilitation programs for the spine , hip , and knee . They are active exercises using body weight for resistance ; thus a clinician is unable to determine the amount of resistance being applied to a muscle group . Electromyographic ( EMG ) analysis can provide a measure of muscle activation so that the clinician can have a better idea about the effect the exercise may have on the muscle for strength , endurance , or stabilization . METHODS AND MEASURES Surface EMG analysis was carried out in 19 males and 11 females while performing the following 9 exercises : active hip abduction , bridge , unilateral-bridge , side-bridge , prone-bridge on the elbows and toes , quadruped arm/lower extremity lift , lateral step-up , st and ing lunge , and using the Dynamic Edge . The rectus abdominis , external oblique abdominis , longissimus thoracis , lumbar multifidus , gluteus maximus , gluteus medius , vastus medialis obliquus , and hamstring muscles were studied . RESULTS In healthy subjects , the lateral step-up and the lunge exercises produced EMG levels greater than 45 % maximum voluntary isometric contraction ( MVIC ) in the vastus medialis obliquus , which suggests that they may be beneficial for strengthening that muscle . The side-bridge exercise could be used for strengthening the gluteus medius and the external oblique abdominis muscles , and the quadruped arm/lower extremity lift exercise may help strengthen the gluteus maximus muscle . All the other exercises produced EMG levels less than 45 % MVIC , so they may be more beneficial for training endurance or stabilization in healthy subjects . CONCLUSION Our results suggest these exercises could be used for a core rehabilitation or performance enhancement program . Depending on the individual needs of a patient or athlete , some of the exercises may be more beneficial than others for achieving strength |
2,262 | 25,010,224 | Conclusion : The majority of the drugs studied in RCTs failed to reduce the incidence of BPD . | Objective : Bronchopulmonary dysplasia ( BPD ) is the most common cause of pulmonary morbidity in premature infants and is associated with life-long morbidities .
Developing drugs for the prevention of BPD would improve public health .
We sought to determine characteristics of favorable r and omized controlled trials ( RCTs ) of drugs for BPD prevention . | Abstract Early inflammatory lesions and bronchial hyperresponsiveness are characteristics of the respiratory distress in premature neonates and are susceptible to aggravation by assisted ventilation . We hypothesized that treatment with inhaled salbutamol and beclomethasone might be of clinical value in the prevention of bronchopulmonary dysplasia ( BPD ) in ventilator-dependent premature neonates . The study was double-blinded and placebo controlled . We studied 173 infants of less than 31 weeks of gestational age , who needed ventilatory support at the 10th postnatal day . They were r and omised to four groups and received either placebo + placebo , placebo + salbutamol , placebo + beclomethasone or beclomethasone + salbutomol , respectively for 28 days . The major criteria for efficacy were : diagnosis of BPD ( with score of severity ) , mortality , duration of ventilatory support and oxygen therapy . The trial groups were similar with respect to age at entry ( 9.8–10.1 days ) , gestational age ( 27.6–27.8 weeks ) , birth weight and oxygen dependence . We did not observe any significant effect of treatment on survival , diagnosis and severity of BPD , duration of ventilatory support or oxygen therapy . For instance , the odds-ratio ( 95 % confidence interval ) for severe or moderate BPD were 1.04 ( 0.52–2.06 ) for inhaled beclomethasone and 1.54 ( 0.78–3.05 ) for inhaled salbutamol . Conclusion This r and omised prospect i ve trial does not support the use of treatment with inhaled beclomethasone , salbutamol or their combination in the prevention of BPD in premature ventilated neonates An imbalance of proinflammatory cytokines such as TNF-alpha , IL-1 beta , and the neutrophil chemotactic factor IL-8 and inhibitors ( e.g. , soluble TNF receptors and IL-1ra ) in the lung during the first week of life may contribute to prolonged pulmonary inflammation and fibrosis in bronchopulmonary dysplasia ( BPD ) . Disodium cromoglycate ( DSCG ) has anti-inflammatory effects in asthma , a disease with many similarities with BPD . In a prospect i ve , r and omized , blinded study , we examined whether early DSCG therapy inhibits proinflammatory cytokines in infants at risk for BPD . Twenty-six infants who were identified as high risk ( > or = 75 % probability ) for oxygen-dependency at 28 d by a 12-h predictive score and survived 48 h were r and omized to nebulized DSCG 20 mg ( n = 13 ) or 2 cc NS ( control , n = 13 ) every 6 h from Day 3 to Day 28 . Lung lavage was collected on Day 3 ( pre- study ) and Day 7 and analyzed for cell count and differential and TNF-alpha , sTNFR1 , sTNFR2 , IL-1 beta , IL-1ra , and IL-8 concentrations . The groups ' pre- study lavage cytokine concentrations were similar , but TNF-alpha and IL-8 concentrations were 3.6- and 4.9-fold lower in the DSCG group on Day 7 compared with levels in the control group . Soluble TNF receptors were unaffected by DSCG . There was a trend towards lower IL-1 beta levels in DSCG-treated infants on Day 7 , but IL-1ra levels were unaffected by DSCG therapy . Three control subjects , but no DSCG-treated infants , died during the study period ( p = 0.07 ) . There were no significant differences between survivors of the two groups for oxygen-dependency at 28 d ( 100 % control subjects ; 85 % DSCG ) . These results suggest that nebulized DSCG may exert an anti-inflammatory effect in the lungs of infants < or = 1,000 g at risk for BPD Background . Although several trials of early dexamethasone therapy have been completed to determine if such therapy would reduce mortality and chronic lung disease ( CLD ) in infants with respiratory distress , optimal duration and side effects of such therapy remain unknown . Purpose . The purpose of this study was : 1 ) to determine if a 3-day course of early dexamethasone therapy would reduce CLD and increase survival without CLD in neonates who received surfactant therapy for respiratory distress syndrome and 2 ) to determine adverse effects associated with such therapy . Design . This was a prospect i ve multicenter r and omized trial comparing a 3-day course of dexamethasone therapy beginning at 24 to 48 hours of life to placebo therapy . Two hundred forty-one neonates ( dexamethasone n = 118 , placebon = 123 ) , who weighed between 500 g and 1500 g , received surfactant therapy , and were at significant risk for CLD or death using a model to predict CLD or death at 24 hours of life , were enrolled in the trial . Infants r and omized to receive early dexamethasone were given 6 doses of dexamethasone at 12-hour intervals beginning at 24 to 48 hours of life . The primary outcomes compared were survival without CLD and CLD . CLD was defined by the need for supplemental oxygen at the gestational age of 36 weeks . Complication rates and adverse effects of study drug therapy were also compared . Results . Neonates r and omized to early dexamethasone treatment were more likely to survive without CLD ( RR : 1.3 ; 95 % CI : 1.03 , 1.7 ) and were less likely to develop CLD ( RR : 0.6 ; CI : 0.3 , 0.98 ) . Mortality rates were not significantly different . Subsequent dexamethasone therapy use was less in early dexamethasone-treated neonates ( RR : 0.8 ; CI : 0.7 , 0.96 ) . Very early ( ≤7 days of life ) intestinal perforations were more common among dexamethasone-treated neonates ( 8 % vs 1 % ) . Conclusion . We conclude that an early 3-day course of dexamethasone therapy increases survival without CLD , reduces CLD , and reduces late dexamethasone therapy in high-risk , low birth weight infants who receive surfactant therapy for respiratory distress syndrome . Potential benefits of early dexamethasone therapy at the dosing schedule used in this trial need to be weighed against the risk for early intestinal perforation OBJECTIVE Since preventive therapies for bronchopulmonary dysplasia ( BPD ) are limited we treated preterm infants with azithromycin to decrease the incidence of BPD . METHODS Infants less than 1,250 g birth weight were r and omized to azithromycin or placebo within 12 hr of beginning mechanical ventilation and within 72 hr of birth . The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for a maximum of 6 weeks . Aspirates were collected during the study to assay for Ureaplasma . The primary endpoints were incidence of BPD or mortality . ( Clinical Trials Identifier : NCT00319956 . ) RESULTS A total of 220 infants were enrolled ( n=111 azithromycin , and 109 placebo ) . Mortality was 18 % for the azithromycin group versus 22 % for the placebo group ( P = 0.45 ) . Incidence of BPD was 76 % for the azithromycin group versus 84 % for the placebo group ( P=0.2 ) . The multiple logistic regression analysis demonstrated an odds ratio of 0.46 decrease in the chance of developing BPD or death for the azithromycin group , but was not statistically significant . The incidence of BPD in the Ureaplasma subgroup was 73 % in the azithromycin group versus 94 % in the placebo group ( P=0.03 ) . Analysis of patients in the Ureaplasma subgroup only , using the exact logistic model demonstrated a decrease in BPD or death in the azithromycin group with an estimated odds ratio of 0.026 ( 0.001 - 0.618 , 95 % confidence interval ) . CONCLUSIONS Routine use of azithromycin therapy for the prevention of BPD can not be recommended . The early treatment of Ureaplasma colonized/infected patients might be beneficial , but a larger multi-centered trial is required to assess this more definitively OBJECTIVES To assess the safety-efficacy balance of low-dose inhaled nitric oxide ( iNO ) in hypoxemic premature infants because no sustained beneficial effect has been demonstrated clearly and there are concerns about side effects . STUDY DESIGN Eight hundred and sixty infants < 32 weeks were r and omized at birth to receive 5 ppm iNO or placebo when they presented with hypoxemic respiratory failure ( HRF ) defined by a requirement for mechanical ventilation , fraction of inspired oxygen ( FIO 2 ) > 40 % , and arterio-alveolar ratio in oxygen ( aAO 2 ) < 0.22 . The primary end point was intact survival at 28 days of age . RESULTS Sixty-one of 415 infants presented with HRF and were compared with 84 of 445 controls who presented with HRF . There was no difference in the primary end point ( 61.4 % in infants [ 23 % with HRF who were treated with iNO ] vs 61.1 % in controls [ 21.4 % in controls with HRF ] ; P = .943 ) . For the infants with HRF who were treated with iNO , there was no significant difference from controls for intraventricular hemorrhage ( IVH ) ( 6 % vs 7 % ) , necrotizing enterocolitis ( 8 % vs 6 % ) , or patent ductus arteriosus ( PDA ) ( 34 % vs 37 % ) . Compared with nonhypoxemic infants , the risk of bronchopulmonary displasia ( BPD ) increased significantly in HRF controls ( OR = 3.264 [ CI 1.461 - 7.292 ] ) but not in infants with HRF who were treated with iNO ( OR = 1.626 [ CI 0.633 - 4.178 ] ) . CONCLUSIONS iNO appears to be safe in premature infants but did not lead to a significant improvement in intact survival on day 28 BACKGROUND AND OBJECTIVE : Effective health care for children must be based on thorough analyses of the best research evidence . The objective of this study was to examine registration , completeness , and publication of studies involving children . METHODS : We search ed the Clinical Trials.gov registry to identify all closed studies involving children and examined them for completeness and availability of results . We examined publication in peer- review ed journals for 160 r and omly selected National Institutes of Health (NIH)–funded studies from 2000 through 2010 and for 758 r and omly selected completed studies . RESULTS : Of 3428 closed studies involving children identified in Clinical Trials.gov , 2385 ( 70 % ) were completed , 28 ( 0.8 % ) suspended , 152 ( 4.4 % ) terminated , and 38 ( 1.1 % ) withdrawn . The proportion of non-completed studies ( terminated and suspended ) increased linearly by 186 % between 2001 and 2009 , from 1.9 % to 8.4 % . Of the 152 terminated studies , 48 did not report reasons for termination , 21 cited safety concerns , and 83 cited poor recruitment or other administrative reasons . Only 29 % of completed studies were published . Publication that did occur was an average of 2 years after study completion . Completed interventional studies were published more often than observational studies . Completed industry-funded studies were published less often than studies funded by the NIH . Registered NIH-funded trials were published more often than unregistered . CONCLUSIONS : Results are unavailable for more than half of the studies involving children , revealing a substantial publication bias . Registration and posting of results on Clinical Trials.gov should be m and atory for all studies involving children Abstract Background : Reactive oxygen species have been considered to play a role in several clinical complications in pre-term infants . The aim of this study was to determine the pharmacokinetics of intravenous N-acetylcysteine in pre-term neonates . This information is needed to evaluate the use of N-acetylcysteine as an antioxidant in this patient group . Methods : N-acetylcysteine was infused intravenously in ten patients ( gestational age 24.9–31.0 weeks , weight 500–1384 g ) for 24 h ( 3.4–4.6 mg/kg/h ) , starting 2.0–11.2 h from birth ( study I ) and in six patients ( gestational age 25.9–29.7 weeks , weight 520–1335 g ) for 6 days ( 0.3–1.3 mg/kg/h ) , starting at the age of 24 h ( study II ) . Arterial plasma N-acetylcysteine and cyst(e)ine concentrations were determined from timed sample s taken during ( study I and II ) and after ( study I ) the N-acetylcysteine infusion . Results : In study I , the mean elimination half-life of N-acetylcysteine was 11 h ( range 7.8–15.2 h ) . The mean plasma clearance of N-acetylcysteine was 37 ml/kg/h ( range 13–62 ml/kg/h ) and the mean volume of distribution was 573 ml/kg ( range 167–1010 ml/kg ) . The plasma clearance and volume of distribution correlated with weight ( r = 0.81 , P < 0.01 , and r = 0.78 , P < 0.01 , respectively ) and with gestational age ( r = 0.71 , P < 0.05 , and r = 0.64 , P < 0.05 , respectively ) . In study II , the steady-state concentration of N-acetylcysteine was reached in 2–3 days in five of six patients during a constant infusion . Conclusions : The pharmacokinetics of N-acetylcysteine in pre-term infants depend markedly on weight and gestational age . The elimination of N-acetylcysteine is much slower in pre-term new-borns than in adults OBJECTIVES To study whether early postnatal ( < 12 hours ) dexamethasone therapy reduces the incidence of chronic lung disease in preterm infants with respiratory distress syndrome . MATERIAL S AND METHODS A multicenter r and omized , double-blind clinical trial was undertaken on 262 ( saline placebo , 130 ; dexamethasone , 132 ) preterm infants ( < 2000 g ) who had respiratory distress syndrome and required mechanical ventilation shortly after birth . The sample size was calculated based on the 50 % reduction in the incidence of chronic lung disease when early dexamethasone is used , allowing a 5 % chance of a type I error and a 10 % chance of a type II error . For infants who received dexamethasone , the dosing schedules were : 0.25 mg/kg/dose every 12 hours intravenously on days 1 through 7 ; 0.12 mg/kg/dose every 12 hours intravenously on days 8 through 14 ; 0.05 mg/kg/dose every 12 hours intravenously on days 15 through 21 ; and 0 . 02 mg/kg/dose every 12 hours intravenously on days 22 through 28 . A st and ard protocol for respiratory care was followed by the participating hospitals . The protocol emphasized the criteria of initiation and weaning from mechanical ventilation . The diagnosis of chronic lung disease based on oxygen dependence and abnormal chest roentgenogram was made at 28 days of age . To assess the effect of dexamethasone on pulmonary inflammatory response , serial tracheal aspirates were assayed for cell counts , protein , leukotriene B4 , and 6-keto prostagl and in F1alpha . All infants were observed for possible side effects , including hypertension , hyperglycemia , sepsis , intraventricular hemorrhage , retinopathy of prematurity , cardiomyopathy , and alterations in calcium homeostasis , protein metabolism , and somatic growth . RESULTS Infants in the dexamethasone group had a significantly lower incidence of chronic lung disease than infants in the placebo group either judged at 28 postnatal days ( 21/132 vs 40/130 ) or at 36 postconceptional weeks ( 20/132 vs 37/130 ) . More infants in the dexamethasone group than in the placebo group were extubated during the study . There was no difference between the groups in mortality ( 39/130 vs 44/132 ) ; however , a higher proportion of infants in the dexamethasone group died in the late study period , probably attributable to infection or sepsis . There was no difference between the groups in duration of oxygen therapy and hospitalization . Early postnatal use of dexamethasone was associated with a significant decrease in tracheal aspirate cell counts , protein , leukotriene B4 , and 6-keto prostagl and in F1alpha , suggesting a suppression of pulmonary inflammatory response . Significantly more infants in the dexamethasone group than in the placebo group had either bacteremia or clinical sepsis ( 43/132 vs 27/130 ) . Other immediate , but transient , side effects observed in the dexamethasone group are : an increase in blood glucose and blood pressure , cardiac hypertrophy , hyperparathyroidism , and a transient delay in the rate of growth . CONCLUSIONS In preterm infants with severe respiratory distress syndrome requiring assisted ventilation shortly after birth , early postnatal dexamethasone therapy reduces the incidence of chronic lung disease , probably on the basis of decreasing the pulmonary inflammatory process during the early neonatal period . Infection or sepsis is the major side effect that may affect the immediate outcome . Other observable side effects are transient . In view of the significant side effects and the lack of overall improvement in outcome and mortality , and the lack of long term follow-up data , the routine use of early dexamethasone therapy is not yet recommended Background Azithromycin reduces the severity of illness in patients with inflammatory lung disease such as cystic fibrosis and diffuse panbronchiolitis . Bronchopulmonary dysplasia ( BPD ) is a pulmonary disorder which causes significant morbidity and mortality in premature infants . BPD is pathologically characterized by inflammation , fibrosis and impaired alveolar development . The purpose of this study was to obtain pilot data on the effectiveness and safety of prophylactic azithromycin in reducing the incidence and severity of BPD in an extremely low birth weight ( ≤ 1000 grams ) population . Methods Infants ≤ 1000 g birth weight admitted to the University of Kentucky Neonatal Intensive Care Unit ( level III , regional referral center ) from 9/1/02 - 6/30/03 were eligible for this pilot study . The pilot study was double-blinded , r and omized , and placebo-controlled . Infants were r and omized to treatment or placebo within 12 hours of beginning mechanical ventilation ( IMV ) and within 72 hours of birth . The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for the duration of the study . Azithromycin or placebo was continued until the infant no longer required IMV or supplemental oxygen , to a maximum of 6 weeks . Primary endpoints were incidence of BPD as defined by oxygen requirement at 36 weeks gestation , post-natal steroid use , days of IMV , and mortality . Data was analyzed by intention to treat using Chi-square and ANOVA . Results A total of 43 extremely premature infants were enrolled in this pilot study . Mean gestational age and birth weight were similar between groups . Mortality , incidence of BPD , days of IMV , and other morbidities were not significantly different between groups . Post-natal steroid use was significantly less in the treatment group [ 31 % ( 6/19 ) ] vs. placebo group [ 62 % ( 10/16 ) ] ( p = 0.05 ) . Duration of mechanical ventilation was significantly less in treatment survivors , with a median of 13 days ( 1–47 days ) vs. 35 days ( 1–112 days)(p = 0.02 ) . Conclusion Our study suggests that azithromycin prophylaxis in extremely low birth weight infants may effectively reduce post-natal steroid use for infants . Further studies are needed to assess the effects of azithromycin on the incidence of BPD and possible less common side effects , before any recommendations regarding routine clinical use can be made Objective : The purpose of this study was to evaluate the effect of early administration of dexamethasone on the incidence of chronic lung disease ( CLD ) in high risk preterm infants and to evaluate the side effects of the early steroid administration . Design : R and omised clinical trial . Setting : Neonatal intensive care unit . Patients : 50 infants at high risk of CLD were r and omly assigned after 72 h of life to the dexamethasone group ( n = 25 ) or to the control group ( n = 25 ) . The treated infants received dexamethasone intravenously from the 4th day of life for 7 days ( 0.5 mg/kg per day for the first 3 days , 0.25 mg/kg per day for the next 3 days and 0.125 mg/kg per day on the 7th day ) . The control group received no steroid treatment . Results : The incidence of CLD at 28 days of life and at 36 weeks ' postconceptional age was significantly lower in the dexamethasone group than in the control group ( p < 0.001 ) . Moreover , infants in the dexamethasone group remained intubated and required oxygen therapy for a shorter period than those in the control group ( p < 0.001 ) . Hyperglycaemia , hypertension , growth failure and mainly hypertrophy of the left ventricle were the transient side effects associated with early steroid administration . Conclusions : Early dexamethasone administration may be useful in preventing CLD , but its use should prudently be restricted to preterm infants at high risk of CLD BACKGROUND Zinc plays a pivotal role in the pathogenesis of many diseases and in body growth . Preterm neonates have high zinc requirements . OBJECTIVE The objective of the study was to investigate the efficacy of zinc supplementation in reducing morbidity and mortality in preterm neonates and to promote growth . DESIGN This was a prospect i ve , double-blind , r and omized controlled study of very-low-birth-weight preterm neonates r and omly allocated on the seventh day of life to receive ( zinc group ) or not receive ( control group ) oral zinc supplementation . Total prescribed zinc intake ranged from 9.7 to 10.7 mg/d in the zinc group and from 1.3 to 1.4 mg/d in the placebo control group . The main endpoint was the rate of neonates with ≥ 1 of the following morbidities : late-onset sepsis , necrotizing enterocolitis , bronchopulmonary dysplasia , periventricular leucomalacia , and retinopathy of prematurity . Secondary outcomes were mortality and body growth . RESULTS We enrolled 97 neonates in the zinc group and 96 in the control group . Morbidities were significantly lower in the zinc group ( 26.8 % compared with 41.7 % ; P = 0.030 ) . The occurrence of necrotizing enterocolitis was significantly higher in the control group ( 6.3 % compared with 0 % ; P = 0.014 ) . Mortality risk was higher in the placebo control group ( RR : 2.37 ; 95 % CI : 1.08 , 5.18 ; P = 0.006 ) . Daily weight gain was similar in the zinc ( 18.2 ± 5.6 g · kg⁻¹ · d⁻¹ ) and control ( 17.0 ± 8.7 g · kg⁻¹ · d⁻¹ ) groups ( P = 0.478 ) . CONCLUSION Oral zinc supplementation given at high doses reduces morbidities and mortality in preterm neonates . This trial was registered in the Australian New Zeal and Clinical Trial Register as ACTRN12612000823875 OBJECTIVE To evaluate whether N-acetylcysteine ( NAC ) infusion during the first week of life reduces the risk of death or bronchopulmonary dysplasia ( BPD ) in infants with extremely low birth weight . Study design In a Nordic multicenter , double-blind trial , infants ( n=391 ) weighing 500 to 999 g and on ventilator or nasal continuous positive airway pressure were r and omized before the age of 36 hours to receive NAC 16 to 32 mg/kg/d ( n=194 ) or placebo ( n=197 ) intravenously for 6 days . Primary end points were death or BPD , defined as supplementary oxygen requirement at 36 weeks ' gestational age . RESULTS There was no difference in the combined incidence of the primary end points death or BPD , 51 % vs. 49 % , between the NAC group and control group . Also similar was the incidence of BPD in survivors at 36 weeks ' gestational age , 40 % vs. 40 % , and the mean oxygen requirement at the age of 28 days , 31.2 % vs. 30.7 % , respectively . The severity of BPD was similar in both groups . CONCLUSIONS A 6-day course of intravenous N-acetylcysteine at the dosage used does not prevent BPD or death in infants with extremely low birth weight Objective . To assess the effect on duration of ventilator dependency of a 42-day tapering course of dexamethasone in very low birth weight neonates . Methods . Infants ( N = 118 ) were assigned r and omly , within birth weight/gender strata , to treatment with either a 42-day tapering course of dexamethasone or an equal volume of saline as placebo . Entry criteria were 1 ) birth weight < 1501 g ; 2 ) age between 15 and 25 days ; 3 ) < 10 % decrease in ventilator setting s for 24 hours and Fio 2 ≥0.3 ; 4 ) absence of patent ductus arteriosus , sepsis , major congenital malformation , congenital heart disease ; and 5 ) no evidence of maternal HIV or hepatitis B infection . The dosage schedule was 0.25 mg/kg bid for 3 days , then 0.15 mg/kg bid for 3 days , then a 10 % reduction in the dose every 3 days until a dose of 0.1 mg/kg had been given for 3 days , from which time a dose of 0.1 mg/kg qod was continued until 42 days after entry . The primary endpoint was the number of days on assisted ventilation after study entry . Secondary outcomes of interest included days on supplemental oxygen , days of hospitalization , and potential adverse effects , such as infection , gastrointestinal bleeding , left ventricular hypertrophy , and severe retinopathy of prematurity . Results . Infants in the dexamethasone- and placebo-treated groups were similar in terms of baseline attributes , including birth weight , gestational age , gender , race , and ventilator setting s at entry . Infants treated with dexamethasone were on assisted ventilation and supplemental oxygen for fewer days after study entry ( median days on ventilator , 5th and 95th percentiles , 13 [ 1–64 ] vs 25 [ 6–104 ] ; days on oxygen , 59 [ 6–247 ] vs 100 [ 11–346 ] ) . No differences were found in risk of death , infection , or severe retinopathy . In subgroup analyses , the association of dexamethasone with more rapid weaning from the ventilator was weaker among infants enrolled before the 16th day of life , infants with chest radiographs showing cystic changes and /or hyperinflation , and infants requiring an Fio 2 ≥0.7 or a peak inspiratory pressure ≥19 at study entry . Conclusions . A 42-day tapering course of dexamethasone decreases the duration of ventilator and oxygen dependency in very low birth weight infants and is not associated with an increased risk of short-term adverse effects The fetus is supplied from the placenta with estradiol ( E2 ) and progesterone ( P ) in increasing amounts during gestation . After delivery of a premature infant , placental supply is disrupted , result ing in a rapid decrease in E2 and P. Replacement of these placental hormones may restore intrauterine conditions and may be beneficial for bone mineral accretion , clinical course , and outcome . Thirty female infants with a median gestational age of 26.6 weeks ( between 24.1 - 28.7 ) and a birth weight of 675 g ( 370 - 990 ) were r and omized to receive E2 and P replacement , aim ing to maintain plasma levels equaling the intrauterine levels , or no replacement . The E2 and P replacement was started iv and was followed by transepidermal administration for a total duration of 6 weeks . Repeated measurements included plasma levels of E2 , P , FSH , and LH ; uterine volume ; calcium and phosphorus in spot urine specimens ; and bone mineral accretion by single photon absorption densitometry . Further , the incidence of chronic lung disease and various clinical outcome data were recorded . The plasma levels of E2 and P were within the intrauterine range with median replacements of 2.30 mg/kg x day E2 ( 1.13 - 6.23 ) and 21.20 mg/kg x day P ( 11.23 - 27.36 ) , iv . Three- and 6-fold higher doses of E2 and P were needed via the transepidermal route . The uterine volumes increased , and FSH and LH as indicators for biological effectiveness were significantly lowered with replacement . The bone mineral accretion rates tended to be higher , and the incidence of chronic lung disease tended to be lower ( 0 % vs. 29 % ; P = 0.097 ) . E2 and P replacement via iv and transepidermal routes is capable of maintaining plasma levels as high as those in utero with biological effectiveness . Trends toward improved postnatal bone mineral accretion and less chronic lung disease were found with the hormone replacement . Further and more extensive studies are warranted to address the role of this new approach in the care of extremely premature infants OBJECTIVE As a first step in the evaluation of recombinant human CuZn superoxide dismutase ( rhSOD ) in the prevention of neonatal lung injury , safety and pharmacokinetics of intratracheally ( IT ) administered rhSOD were studied . METHODS Twenty-six preterm infants weighing 750 to 1250 g with respiratory distress syndrome were studied in three sequential groups ( placebo , 0.5 , and 5 mg/kg ) . Placebo or rhSOD was administered IT 30 minutes after the first surfactant dose . Serial blood and urine studies , rhSOD levels , tracheal aspirate fluid ( TAF ) markers of acute inflammation , radiographs , and ultrasounds were performed over the 28-day study period . RESULTS Serum SOD concentrations were similar at baseline for all three groups ( geometric mean 0.2 , upper-lower limit 0.1 to 0.2 microgram/mL ) . In the 0.5-mg/kg group , levels were highest at 12 hours ( geometric mean 0.7 , upper-lower limit 0.5 to 0.8 microgram/mL ) and returned to baseline by day 3 . In the 5-mg/kg group , levels were highest at 6 hours ( geometric mean 3.0 , upper-lower limit 2.3 to 4.0 micrograms/mL ) and returned to baseline by day 4 . Concentrations of SOD in TAF were also similar at baseline for all three groups ( geometric mean 0.2 , upper-lower limit 0.2 to 0.3 microgram/mL ) . There were no significant increases in the placebo group , but levels in the 0.5-mg/kg group were highest when first sample d at 24 hours ( geometric mean 1.1 , upper-lower limit 0.8 to 1.4 micrograms/mL ) and returned to baseline by day 3 . In the 5-mg/kg group , levels were also highest when sample d at 24 hours ( geometric mean 1.4 , upper-lower limit 0.9 to 2.1 micrograms/mL ) and returned to baseline by day 4 . Urine levels were highest at 12 hours in both the 0.5-mg/kg ( geometric mean 1.3 , upper-lower limit 1.0 to 1.7 micrograms/mL ) and 5-mg/kg infants ( geometric mean 6.4 , upper-lower limit 3.9 to 10.4 micrograms/mL ) and decreased significantly by day 2 to 3 . rhSOD activity assays ( serum , TAF , and urine ) demonstrated that the enzyme still possessed significant activity . No adverse effects of rhSOD were found . TAF neutrophil chemotactic activity and albumin concentrations , important acute lung injury markers , were significantly lower in the high-dose rhSOD group compared with the other groups . CONCLUSIONS Data suggest that a single IT dose of rhSOD results in significant increases in both concentration and activity of the antioxidant in serum , TAF , and urine for 2 to 3 days . The enzyme appears to be well tolerated , and TAF inflammatory markers are reduced after administration . This has important implication s in rhSOD trials to prevent acute and chronic lung injury in preterm neonates BACKGROUND The safety and efficacy of inhaled glucocorticoid therapy for asthma stimulated its use in infants to prevent bronchopulmonary dysplasia . We tested the hypothesis that early therapy with inhaled glucocorticoids would decrease the frequency of bronchopulmonary dysplasia in premature infants . METHODS We conducted a r and omized , multicenter trial of inhaled beclomethasone or placebo in 253 infants , 3 to 14 days old , born before 33 weeks of gestation and weighing 1250 g or less at birth , who required ventilation therapy . Beclomethasone was delivered in a decreasing dosage , from 40 to 5 microg per kilogram of body weight per day , for four weeks . The primary outcome measure was bronchopulmonary dysplasia at 28 days of age . Secondary outcomes included bronchopulmonary dysplasia at 36 weeks of postmenstrual age , the need for systemic glucocorticoid therapy , the need for bronchodilator therapy , the duration of respiratory support , and death . RESULTS One hundred twenty-three infants received beclomethasone , and 130 received placebo . The frequency of bronchopulmonary dysplasia was similar in the two groups : 43 percent in the beclomethasone group and 45 percent in the placebo group at 28 days of age , and 18 percent in the beclomethasone group and 20 percent in the placebo group at 36 weeks of postmenstrual age . At 28 days of age , fewer infants in the beclomethasone group than in the placebo group were receiving systemic glucocorticoid therapy ( relative risk , 0.6 ; 95 percent confidence interval , 0.4 to 1.0 ) and mechanical ventilation ( relative risk , 0.8 ; 95 percent confidence interval , 0.6 to 1.0 ) . CONCLUSIONS Early beclomethasone therapy did not prevent bronchopulmonary dysplasia but was associated with lower rates of use of systemic glucocorticoid therapy and mechanical ventilation OBJECTIVE Inconsistent effects of vitamin A supplementation on prevention of bronchopulmonary dysplasia have been reported . Meta- analysis of these reports result ed in a relative risk of 0.69 - 1.02 for death or bronchopulmonary dysplasia associated with vitamin A supplementation . Effective dosage regimens or serum retinol concentrations have not been determined in previous reports . The purpose of this pilot study was to define a vitamin A regimen that produces serum retinol concentrations of 25 - 55 micrograms/dl . STUDY DESIGN In this three-phase study , 91 infants ( mean birth weight 799 - 864 g ) were enrolled . Vitamin A was administered three times/week for 4 weeks at an average daily dose of 986 - 2143 IU/day . Physical examinations were performed and serum retinol specimens were collected weekly to assess clinical signs of toxicity . RESULTS The majority of serum retinol concentrations remained < 25 micrograms/dl until an intramuscular vitamin A dose of 5000 IU/dose three times/week was used . No clinical signs of toxicity were associated with the higher dosage and higher serum concentrations of vitamin A. CONCLUSION A large clinical trial of vitamin A supplementation with 5000 IU/dose three times/week ( 25 - 114 % more than the dose used in the three published clinical trials ) is needed to assess whether vitamin A supplementation safely reduces the risk of bronchopulmonary dysplasia in very-low-birth-weight infants OBJECTIVE : To evaluate the efficacy and safety of clarithromycin treatment in preventing bronchopulmonary dysplasia ( BPD ) in Ureaplasma urealyticum – positive preterm infants . PATIENTS AND METHODS : Nasopharyngeal swabs for U urealyticum culture were taken from infants with a birth weight between 750 and 1250 g in the first 3 postnatal days . Infants with a positive culture for U urealyticum were r and omly assigned to 1 of 2 groups to receive either intravenous clarithromycin or placebo . All the patients were followed at least up to the 36th postmenstrual week . RESULTS : A total of 224 infants met the eligibility criteria of the study . Seventy-four ( 33 % ) infants had a positive culture for U urealyticum in the first 3 day cultures . The rate of BPD development was significantly higher in patients with U urealyticum positivity ( 15.9 % vs 36.4 % ; P < .01 ) . However , multivariate logistic regression analysis failed to reveal a significant association between the presence of U urealyticum and BPD development ( odds ratio : 2.4 [ 95 % confidence interval : 0.9–6.3 ] ; P = .06 ) . Clarithromycin treatment result ed in eradication of U urealyticum in 68.5 % of the patients . The incidence of BPD was significantly lower in the clarithromycin group than in the placebo group ( 2.9 % vs 36.4 % ; P < .001 ) . Multivariate logistic regression analysis confirmed the independent preventive effect of clarithromycin for the development of BPD ( odds ratio : 27.2 [ 95 % confidence interval : 2.5–296.1 ] ; P = .007 ) . CONCLUSIONS : Clarithromycin treatment prevents development of BPD in preterm infants who are born at 750 to 1250 g and colonized with U urealyticum We performed a r and omized , double-blind , controlled trial to determine whether vitamin A supplementation in a group of very low birth weight infants would reduce the incidence of bronchopulmonary dysplasia . Forty-nine infants ( birth weight 700 to 1100 gm ) requiring mechanical ventilation and supplemental oxygen at 96 hours age were r and omly assigned to receive either 2000 IU retinyl palmitate ( n = 27 ) or saline placebo ( n = 22 ) intramuscularly every other day for up to 14 doses . There were no differences between treatment groups in the incidences of bronchopulmonary dysplasia at 31 days of postnatal age ( vitamin A group 48 % , placebo group 55 % ; p = 0.776 ) , supplemental oxygen requirement at 34 weeks of postconceptional age , or other complications of prematurity . The vitamin A group had higher mean plasma vitamin A concentrations than the placebo group , but mean plasma vitamin A concentrations were greater than 20 micrograms/dl ( suggesting sufficiency ) in both groups after the first study week . By study day 28 , only one fourth of the infants in either group had plasma vitamin A concentrations less than 20 micrograms/dl . In contrast to an earlier report , we found no change in the incidence of BPD with vitamin A supplementation . Our findings may reflect a low baseline incidence of vitamin A deficiency in the study population and recent changes in the respiratory care of very low birth weight infants . The latter may have lessened the potential impact of vitamin A deficiency on lung disease ABSTRACT Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia ( BPD ) in preterm infants . Previously , we demonstrated that a single intravenous ( i.v . ) dose of azithromycin ( 10 mg/kg of body weight ) is safe but inadequate to eradicate Ureaplasma spp . in preterm infants . We performed a nonr and omized , single-arm open-label study of the pharmacokinetics ( PK ) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days . Pharmacokinetic data from 25 neonates ( 12 dosed with 10 mg/kg i.v . and 13 dosed with 20 mg/kg i.v . ) were analyzed using a population modeling approach . Using a two-compartment model with allometric scaling of parameters on body weight ( WT ) , the population PK parameter estimates were as follows : clearance , 0.21 liter/h × WT(kg)0.75 [ WT(kg)0.75 indicates that clearance was allometrically scaled on body weight ( in kilograms ) with a fixed exponent of 0.75 ] ; intercompartmental clearance , 2.1 liters/h × WT(kg)0.75 ; central volume of distribution ( V ) , 1.97 liters × WT ( kg ) ; and peripheral V , 17.9 liters × WT ( kg ) . There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range . The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90 ( AUC24/MIC90 ) for the single dose of azithromycin ( 20 mg/kg ) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of > MIC50 of 1 μg/ml for this group of Ureaplasma isolates for ≥96 h after the first dose . Azithromycin was well tolerated with no drug-related adverse events . One of seven ( 14 % ) Ureaplasma-positive subjects and three of six ( 50 % ) Ureaplasma-negative subjects developed physiologic BPD . Ureaplasma was eradicated in all treated Ureaplasma-positive subjects . Simulations suggest that a multiple-dose regimen may be efficacious for microbial clearance , but the effect on BPD remains to be determined AIM To investigate the therapeutic efficacy of inhaled fluticasone propionate , started on day 1 of age , on ventilated preterm infants with respiratory distress syndrome . METHODS Starting within 24 hours of age , ventilated preterm infants ( gestation < 32 weeks , birthweight < 1.5 kg ) with respiratory distress syndrome were given a 14 day course ( two puffs , 12 hourly ) of either fluticasone propionate ( 250 μg/puff ) ( group 1 , n=27 ) or placebo ( group 2 , n=26 ) with a metered dose inhaler – spacer device . Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age , changes in respiratory system mechanics , death , occurrence of chronic lung disease , and other neonatal complications . RESULTS More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group ( 17/27 vs8/26 ; p = 0.038 ) . The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life . The two groups , however , did not differ significantly in their need for systemic steroids after day 14 of age , death , or the occurrence of chronic lung disease . The treatment was not associated with any increase in neonatal complications , including those attributable to steroid induced side effects . CONCLUSION These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress . Further study of its use in a large scale r and omised trial is warranted Objective . Bronchopulmonary dysplasia ( BPD ) is the endpoint of many intervention trials in neonatology , yet the outcome measure when based solely on oxygen administration may be confounded by differing criteria for oxygen administration between physicians . We previously reported a technique to st and ardize the definition of BPD between sites by using a timed room-air challenge in selected infants . We hypothesized that a physiologic definition of BPD would reduce the variation in observed rates of BPD among different neonatal centers . Methodology . A total of 1598 consecutive inborn premature infants ( 501–1249 g birth weight ) who remained hospitalized at 36 weeks ' postmenstrual age were prospect ively assessed and assigned an outcome with both a clinical definition and physiologic definition of BPD . The clinical definition of BPD was oxygen supplementation at exactly 36 weeks ' postmenstrual age . The physiologic definition of BPD was assigned at 36 ± 1 weeks ' postmenstrual age and included 2 distinct sub population s. First , neonates on positive pressure support or receiving > 30 % supplemental oxygen with saturations between 90 % and 96 % were assigned the outcome BPD and not tested further . Second , those receiving ≤30 % oxygen or effective oxygen > 30 % with saturations > 96 % underwent a room-air challenge with continuous observation and oxygen-saturation monitoring . Outcomes of the room-air challenge were “ no BPD ” ( saturations ≥90 % during weaning and in room air for 30 minutes ) or “ BPD ” ( saturation < 90 % ) . At the conclusion of the room-air challenge , all infants were returned to their baseline oxygen levels . Safety ( apnea , bradycardia , increased oxygen use ) and outcomes of the physiologic definition versus the clinical definition were assessed . Results . A total of 560 ( 35.0 % ) neonates were diagnosed with BPD by the clinical definition of oxygen use at 36 weeks ' postmenstrual age . The physiologic definition diagnosed BPD in 398 ( 25.0 % ) neonates in the cohort . All infants were safely studied . There were marked differences in the impact of the definition on BPD rates between centers ( mean reduction : 10 % ; range : 0–44 % ) . Sixteen centers had a decrease in their BPD rate , and 1 center had no change in their rate . Conclusions . The physiologic definition of BPD reduced the overall rate of BPD and reduced the variation among centers . Significant center differences in the impact of the physiologic definition were seen , and differences remained even with the use of this st and ardized definition . The magnitude of the change in BPD rate is comparable to the magnitude of treatment effects seen in some clinical trials in BPD . The physiologic definition of BPD facilitates the measurement of BPD as an outcome in clinical trials and the comparison between and within centers over time UNLABELLED BACKGROUND . Many extremely low birth weight infants ( < 1000 g ) show biochemical evidence of adrenal insufficiency in the first week of life , correlating with subsequent development of chronic lung disease ( CLD ) . METHODS We conducted a r and omized , double-masked , placebo-controlled pilot study to test whether early treatment with low-dose hydrocortisone for 12 days ( 1 mg/kg/day for 9 days followed by.5 mg/kg/day for 3 days ) , begun before 48 hours of life , would increase the likelihood of survival without CLD . RESULTS Forty patients were enrolled at two centers . Birth weight and gestation were similar for treatment and placebo groups : 732 + /- 135 g versus 770 + /- 135 g and 25.2 + /- 1.3 weeks versus 25.4 + /- 1.5 weeks . More infants treated with hydrocortisone achieved study success , defined as survival without supplemental oxygen at 36 weeks ' postconception ( 12/20 [ 60 % ] vs 7/20 [ 35 % ] ) . Lower birth weight , histologic chorioamnionitis , and preeclampsia were significant risk factors , whereas study center , prenatal steroids , sex , and ethnicity were not significant . Hydrocortisone treatment decreased days on > 40 % oxygen , days on > 25 % oxygen , days on ventilator , and oxygen at discharge . Among infants exposed to chorioamnionitis , hydrocortisone treatment also was associated with increased enteral intake during the first month of life and with increased weight at 36 weeks ' postconception . Five treated infants and 6 placebo infants developed sepsis ; 3 in each group died . CONCLUSIONS First , early treatment with low-dose hydrocortisone in this population of extremely low birth weight infants increased the likelihood of survival without CLD . Second , the benefit was particularly apparent in infants with chorioamnionitis . Third , a larger multicenter trial is needed to verify the primary outcome and to better evaluate risks and benefits Background : Myo-inositol given to preterm infants with respiratory distress has reduced death , increased survival without bronchopulmonary dysplasia , and reduced severe retinopathy of prematurity in two r and omized trials . Pharmacokinetic ( PK ) studies in extremely preterm infants are needed before efficacy trials . Methods : Infants born in 23–29 wk of gestation were r and omized to a single intravenous ( i.v . ) dose of inositol at 60 or 120 mg/kg or placebo . Over 96 h , serum levels ( sparse sampling population PK ) and urine inositol excretion were determined . Population PK models were fit using a nonlinear mixed-effects approach . Safety outcomes were recorded . Results : A single-compartment model that included factors for endogenous inositol production , allometric size based on weight , gestational age strata , and creatinine clearance fit the data best . The central volume of distribution was 0.5115 l/kg , the clearance was 0.0679 l/kg/h , endogenous production was 2.67 mg/kg/h , and the half-life was 5.22 h when modeled without the covariates . During the first 12 h , renal inositol excretion quadrupled in the 120 mg/kg group , returning to near-baseline value after 48 h. There was no diuretic side effect . No significant differences in adverse events occurred among the three groups ( P > 0.05 ) . Conclusion : A single-compartment model accounting for endogenous production satisfactorily described the PK of i.v . inositol ABSTRACT : Bronchopulmonary dysplasia is an important complication of ventilation in babies for which treatment with steroids has been advocated . We report the results of a phase I study of early i.v . dexamethasone to prevent the development of bronchopulmonary dysplasia in a high-risk population of ventilated premature babies , < 30 wk gestation , with surfactant-treated respiratory distress syndrome . This study used a limited dexamethasone dosing regimen to minimize toxicity but used administration early in the course of acute lung disease to interrupt the injury cycle . Forty babies were enrolled ; 19 were r and omized to receive dexamethasone ( 0.5 mg/kg birth weight at 12–18 h of age and a second dose 12 h later ) and 21 were r and omized to receive placebo ( i.v . saline ) . The dexamethasone group required less ventilatory support ( mean airway , peak in-spiratory and end expiratory pressures , and intermittent m and atory ventilation ) and supplemental oxygen after study d 4 ( all p < 0.05 , repeated measures analysis of variance ) . Improved tidal volume in the dexamethasone group , as measured by pulmonary function testing of infants who remained intubated , was seen on study d 7 ( p = 0.02 , t test ) . The dexamethasone group required shorter hospitalizations ( median of 95 d versus 106 d , p = 0.01 ) ( proportional hazards regression ) . Survival in the dexa methasone group was 89 % versus 67 % in the placebo group ( p = 0.08 , x2 analysis ) . Survival without bronchopulmonary dysplasia , diagnosed at 36 wk corrected gestational age , was 68 % in the dexamethasone group versus 43 % in the placebo group ( p = 0.14 ) . Mean blood pressure was elevated on study d 4 through 7 in the dexamethasone group , but this difference resolved by study d 10 without pharmacologic intervention . No differences in hyperglycemia , incidence of intraventricular hemorrhage ( or its severity ) , or days to regain birth weight were seen . Early administration of dexamethasone result ed in short-term and suggested long-term benefits without significant complications . The results of this trial justify a large scale , broader-based ( phase II ) trial in premature babies with respiratory distress syndrome to determine the limits of effectiveness and the incidence of less-frequent potential side effects In a multicenter , double-blind , placebo-controlled trial conducted at 23 hospitals in the United States , a single prophylactic 5 ml/kg dose of a synthetic surfactant ( Exosurf Neonatal ) or air placebo was administered shortly after birth to 215 infants with birth weights of 500 to 699 gm . Despite stratification at entry by birth weight and gender , by chance female infants predominated in the air placebo group and male infants predominated in the surfactant group . Among infants receiving synthetic surfactant , improvements in oxygen requirements were significant at 2 hours after birth ( p = 0.014 ) and persisted for 3 days ( p = 0.001 ) ; improvements in the alveolar-arterial partial pressure of oxygen gradient were significant at 6 hours after birth ( p = 0.01 ) and persisted for 3 days ( p = 0.008 ) . Improvements in mean airway pressure were not significant at 2 or at 6 hours after birth ( p = 0.622 and 0.083 , respectively ) , but became significant thereafter and persisted for 3 days ( p = 0.002 ) . Pneumothorax was reduced by slightly more than half ( 25 vs 11 ; p = 0.014 ) ; death from respiratory distress syndrome ( RDS ) was also reduced ( 26 vs 15 ; p = 0.046 ) . Overall neonatal mortality , however , was not significantly reduced ( 58 vs 46 ; p = 0.102 ) . Other complications of RDS and prematurity were not altered , except that pulmonary hemorrhage occurred significantly more frequently in infants receiving synthetic surfactant ( 2 vs 12 ; p = 0.006 ) . These findings indicate that a single prophylactic dose of synthetic surfactant in infants weighing 500 to 699 gm at birth improves lung function , incidence of air leak , and death from RDS but not overall mortality . The only safety problem identified was an increase in pulmonary hemorrhage Background . We previously demonstrated improved survival and early outcomes in a pilot trial of 2 doses of intravenous dexamethasone for infants with surfactant-treated respiratory distress syndrome.1 A multicenter , r and omized , double-blind trial was undertaken to confirm these results . Methods . Infants < 30 weeks ' gestation were eligible if they had respiratory distress syndrome , required mechanical ventilation at 12 to 18 hours of age , and had received at least 1 dose of exogenous surfactant . Infants were excluded if sepsis or pneumonia was suspected or if congenital heart disease or chromosomal abnormalities were present . A total of 384 infants were enrolled—189 r and omized to dexamethasone ( .5mg/kg birth weight at 12–18 hours of age and a second dose 12 hours later ) and 195 to an equal volume of saline placebo . Results . No differences were found in the dexamethasone versus placebo groups , respectively , regarding the primary outcomes of survival ( 79 % vs 83 % ) , survival without oxygen at 36 weeks ' corrected gestational age ( CGA ; both 59 % ) , and survival without oxygen at 36 weeks ' CGA and without late glucocorticoid therapy ( 46 % vs 44 % ) . No significant differences between the groups in estimates from Kaplan-Meier survival analyses were found for median days on oxygen ( 50 vs 56 days ) , ventilation ( 20 vs 27 days ) , days to regain birth weight ( 15.5 vs 14 days ) , or length of stay ( LOS ; 88 vs 89 days ) . Infants given early dexamethasone were less likely to receive later glucocorticoid therapy for bronchopulmonary dysplasia during their hospitalization ( 27 % vs 35 % ) . No clinical ly significant side effects were noted in the dexamethasone group , although there were transient elevations in blood glucose and blood pressure followed by a return to baseline by study day 10 . Among infants who died ( 40 vs 33 ) , there were no differences in the median days on oxygen , ventilation , nor LOS . However , in survivors ( 149 vs 162 ) , the following were observed : median days on oxygen 37 versus 45 days , ventilation 14 versus 19 days , and LOS 79 versus 81 days , for the dexamethasone versus placebo groups , respectively . Conclusions . This dose of early intravenous dexamethasone did not reduce the requirement for oxygen at 36 weeks ' CGA and survival was not improved . However , early dexamethasone reduced the use of later prolonged dexamethasone therapy , and among survivors , reduced the median days on oxygen and ventilation . We conclude that this course of early dexamethasone probably represents a near minimum dose for instituting a prophylactic regimen against bronchopulmonary dys- plasia Recent studies suggest that early dexamethasone therapy may lessen the pulmonary inflammation in preterm infants with respiratory distress syndrome ( RDS ) . To investigate whether early ( < 12 hr ) postnatal dexamethasone therapy would reduce the incidence of chronic lung disease ( CLD ) , a r and omized , double-blind , controlled trial was conducted in 40 infants ( birth weights from 500 to 1,999 gm ) who had severe RDS and required mechanical ventilation within 6 hr of birth . All infants received one dose of Survanta before they were r and omly assigned to control ( saline placebo ) or dexamethasone-treated groups ( 0.5 mg/kg/d for 1 week , then tapered over 3 weeks ) . Sequential analysis was performed with the end point of assessment being the presence or absence of CLD on postnatal Day 28 . Statistical significance favoring dexamethasone was reached when 12 consecutive pairs in which one infant had CLD and the other did not have CLD showed that ten pairs favored dexamethasone and two pairs favored control treatment . Among the survivors , 12/15 were extubated in the dexamethasone group and 9/16 in the control group at the end of study . Infants in the treated group had transient hyperglycemia and hypertension . There was no difference between the groups in mortality and in incidence of sepsis or intraventricular hemorrhage . We conclude that early postnatal dexamethasone therapy is potentially effective in the lessening of CLD in preterm infants . To substantiate our result , large r and omized controlled trials are needed and warranted OBJECTIVES This study was carried to evaluate the effect of early administration of dexamethasone on the incidence of bronchopulmonary dysplasia ( BPD ) and /or death in surfactant-treated preterm infants with respiratory distress syndrome ( RDS ) . STUDY DESIGN In a multicenter , double-blind , placebo-controlled trial , 109 preterm infants with RDS and birth weights between 700 and 1600 gm , who were treated with mechanical ventilation and surfactant , were r and omly assigned before 36 hours of life to receive dexamethasone ( n = 55 ) or placebo ( n = 54 ) for 12 days . RESULTS There were no differences in the incidence of BPD and /or death between groups . However , fewer patients in the dexamethasone group were oxygen-dependent at 36 weeks after conception ( 8 % vs 33 % , p < 0.05 ) . The dexamethasone group had a lower incidence of necrotizing enterocolitis ( 0 % vs 9 % , p < 0.05 ) . The incidence of arterial hypertension , hyperglycemia , and sepsis was not affected by the treatment . Basal and poststimulation serum cortisol levels did not differ between groups . CONCLUSION The administration of dexamethasone early in the course of RDS does not decrease the incidence of BPD and /or death in preterm infants . However , dexamethasone may reduce oxygen dependency at 36 weeks after conception BACKGROUND Vitamin A supplementation may reduce the risk of chronic lung disease and sepsis in extremely-low-birth-weight infants . The results of our pilot study suggested that a dose of 5000 IU administered intramuscularly three times per week for four weeks was more effective than the lower doses given in past trials . METHODS We performed a multicenter , blinded , r and omized trial to assess the effectiveness and safety of this regimen as compared with sham treatment in 807 infants in need of respiratory support 24 hours after birth . The mean birth weight was 770 g in the vitamin A group and 769 g in the control group , and the respective gestational ages were 26.8 and 26.7 weeks . RESULTS By 36 weeks ' postmenstrual age , 59 of the 405 infants ( 15 percent ) in the vitamin A group and 55 of the 402 infants ( 14 percent ) in the control group had died . The primary outcome - death or chronic lung disease at 36 weeks ' postmenstrual age - occurred in significantly fewer infants in the vitamin A group than in the control group ( 55 percent vs. 62 percent ; relative risk , 0.89 ; 95 percent confidence interval , 0.80 to 0.99 ) . Overall , 1 additional infant survived without chronic lung disease for every 14 to 15 infants who received vitamin A supplements . The proportions of infants in the vitamin A group and the control group who had signs of potential vitamin A toxicity were similar . The proportion of infants with serum retinol values below 20 microg per deciliter ( 0.70 micromol per liter ) was lower in the vitamin A group than in the control group ( 25 percent vs. 54 percent , P<0.001 ) . CONCLUSIONS Intramuscular administration of 5000 IU of vitamin A three times per week for four weeks reduced biochemical evidence of vitamin A deficiency and slightly decreased the risk of chronic lung disease in extremely-low-birth-weight infants OBJECTIVES : To determine ( 1 ) the magnitude of clustering of bronchopulmonary dysplasia ( 36 weeks ) or death ( the outcome ) across centers of the Eunice Kennedy Shriver National Institute of Child and Human Development National Research Network , ( 2 ) the infant-level variables associated with the outcome and estimate their clustering , and ( 3 ) the center-specific practice s associated with the differences and build predictive models . METHODS : Data on neonates with a birth weight of < 1250 g from the cluster-r and omized benchmarking trial were used to determine the magnitude of clustering of the outcome according to alternating logistic regression by using pairwise odds ratio and predictive modeling . Clinical variables associated with the outcome were identified by using multivariate analysis . The magnitude of clustering was then evaluated after correction for infant-level variables . Predictive models were developed by using center-specific and infant-level variables for data from 2001 2004 and projected to 2006 . RESULTS : In 2001–2004 , clustering of bronchopulmonary dysplasia/death was significant ( pairwise odds ratio : 1.3 ; P < .001 ) and increased in 2006 ( pairwise odds ratio : 1.6 ; overall incidence : 52 % ; range across centers : 32%–74 % ) ; center rates were relatively stable over time . Variables that varied according to center and were associated with increased risk of outcome included lower body temperature at NICU admission , use of prophylactic indomethacin , specific drug therapy on day 1 , and lack of endotracheal intubation . Center differences remained significant even after correction for clustered variables . CONCLUSION : Bronchopulmonary dysplasia/death rates demonstrated moderate clustering according to center . Clinical variables associated with the outcome were also clustered . Center differences after correction of clustered variables indicate presence of as-yet unmeasured center variables Thirty-two neonates weighing 500 - 1500 g with documented surfactant deficiency and without evidence of severe birth asphyxia , infection , prolonged rupture of membranes greater than or equal to 72 h , or oligohydramnios were r and omly assigned to receive a single intratracheal dose of surfactant-TA ( 100 mg/kg ) either within 30 min of birth ( n = 16 , early group ) or at 6 h of age ( n = 16 , late group ) . By 6 h of age , all neonates of the late group had moderate/severe RDS , while none of the neonates of the early group had either clinical or radiological respiratory distress syndrome . The incidence of bronchopulmonary dysplasia was significantly lower in survivors of the early group than those of the late group ( 1/15 versus 7/14 , a 43 % reduction with a 95 % confidence interval of 14 - 72 % , P = 0.025 ) . These beneficial effects of early surfactant treatment remained after controlling for the various confounding factors in the logistic models BACKGROUND Surfactant therapy now has a well-established role in the treatment of neonates with respiratory distress syndrome but has failed to reduce the incidence of bronchopulmonary dysplasia ( BPD ) . We conducted a double-blind , placebo-controlled trial to test the hypothesis that dexamethasone therapy given during the first 12 days of life to very low birth weight infants would be synergistic to surfactant in preventing BPD . METHODS Seventy surfactant-pretreated infants ( 700 - 1500 g ) who had severe respiratory distress syndrome ( a/A ratio , 0.18 + /- 0.10 ; mean airway pressure , 11.1 + /- 1.9 cm H2O ; fraction of inspired oxygen , 0.81 + /- 0.22 ) were enrolled to receive a 12-day course of dexamethasone ( n = 36 ) or saline placebo ( n = 34 ) starting within the first 12 hours after birth . The starting dose of dexamethasone was 0.5 mg/kg per day , and it was tapered progressively . RESULTS Ventilator variables at 5 to 14 days were significantly improved in those infants who received dexamethasone compared with those who received the placebo . The effect seem to be more marked in infants weighting less than 1250 g at birth . Significantly more infants could be extubated by 14 days of age in the dexamethasone group ( 26 of 32 vs 14 of 32 ) . Dexamethasone therapy reduced the incidence of BPD at 28 days ( odds ratio , 0.1 ; 95 % confidence interval , 0.03 to 0.3 ) and eliminated BPD at 36 weeks ' postconceptional age . Dexamethasone-treated infants had greater weight loss at 14 days ( 12.9 + /- 6.4 % vs 3.7 + /- 8.6 % , respectively ) and higher blood pressures from days 3 to 10 . However , no differences were seen in time to regain birth weight , hypertension ( 1 infant in each group ) , or incidence of intraventricular hemorrhage . CONCLUSIONS We found an additive effect between dexamethasone and surfactant in improving pulmonary status and reducing the incidence of BPD . Compared with the placebo , dexamethasone therapy was more effective in reducing the incidence of BPD in surfactant-pretreated very low birth weight infants In a multicenter , double-blind , placebo-controlled rescue trial conducted at 13 Canadian hospitals , two 5 ml/kg doses of a synthetic surfactant or air placebo were administered to 344 infants with birth weights of 750 to 1249 gm who had established respiratory distress syndrome and an arterial/alveolar oxygen tension ratio less than 0.22 . The first dose was given between 2 and 24 hours of age , and the second dose was given 12 hours later to the infants remaining on mechanical ventilation . Infants were stratified at study entry by birth weight and gender . The trial was terminated short of the targeted sample size because significant reductions in mortality were observed in another rescue trial completed in the United States in the same weight class of infants . Despite premature termination of the trial , the rate of survival without bronchopulmonary dysplasia was increased ( 61 % vs 52 % ; p = 0.046 ) in infants treated with surfactant . In addition , there was a significant reduction in the incidence of overall pulmonary air leak ( 46 % vs 32 % ; p = 0.009 ) , pneumothorax ( 27 % vs 17 % ; p = 0.023 ) , and pulmonary interstitial emphysema ( 40 % vs 28 % ; p = 0.018 ) in infants treated with synthetic surfactant . There was no difference in the incidence of bronchopulmonary dysplasia , apnea , or pulmonary hemorrhage . Significant improvements in alveolar-arterial oxygen tension gradient , arterial/alveolar oxygen tension ratio , and oxygen and ventilator requirements through day 7 were present . These findings indicate that rescue therapy with synthetic surfactant can improve outcome for premature infants weighing 750 to 1249 gm with respiratory distress syndrome OBJECTIVE To determine the effect of bovine surfactant ( SF-RI 1 , Alveofact ) administered during the first hour following birth to very premature infants [ gestational age ( GA ) , 25 - 30 weeks ] in a multicenter , controlled trial . HYPOTHESIS Survival without bronchopulmonary dysplasia ( BPD ; definition : ventilator dependency or FiO2 greater than 0.3 during spontaneous respiration ) at day 28 is increased in surfactant-treated infants ( sequential analysis ) . PATIENTS AND METHODS Thirty-four infants [ GA 28.0 + /- 1.5 SD weeks , birth weight ( BW ) , 1,048 + /- 299 g ] received 50 mg/kg BW surfactant , whereas 35 infants ( GA , 27.6 + /- 1.5 weeks , BW 969 + /- 269 g ) served as controls . Retreatment with surfactant ( up to three identical doses ) 12 - 24 hours after the previous dose was permitted if FiO2 was greater than 0.5 . RESULTS Survival without BPD was significantly higher in surfactant treated infants ( 26/34 ) compared to controls ( 14/35 ; P = 0.003 ) , but in the incidence of pulmonary air leaks , patent ductus arteriosus , intracranial hemorrhage , and nosocomial infections they were not different . CONCLUSION Bovine surfactant treatment improves survival without BPD in very premature infants at risk for neonatal respiratory distress syndrome ( RDS ) |
2,263 | 19,082,392 | In conclusion , NaOCl or CHX showed low ability to eliminate E. faecalis when evaluated by either PCR or culture techniques | The efficacy of the sodium hypochlorite ( NaOCl ) and chlorhexidine ( CHX ) on Enterococcus faecalis was evaluated by systematic review and meta- analysis . | AIMS The aim of this study was to determine the occurrence and role of yeasts , enteric gram-negative rods and Enterococcus species in root-filled teeth with chronic apical periodontitis , and the antimicrobial effect of iodine potassium iodide ( IKI ) irrigation . METHODOLOGY Forty symptom-free root-filled teeth with chronic apical periodontitis were included in the study . The patients were divided into two groups . In group A the canals were filled with calcium hydroxide for 10 - 14 days after cleaning and shaping ; in group B the canals were irrigated with IKI for 5 min after cleaning and shaping followed by a permanent root filling . Microbiological sample s were taken from the canals before and after the chemomechanical preparation and after iodine irrigation ( group B ) . RESULTS Microbes were isolated from 33 of 40 teeth in the initial sampling . Yeasts were isolated from six teeth , three of them together with E. faecalis . Enteric rods ( Escherichia coli , Klebsiella pneumoniae and Proteus mirabilis ) were present in three teeth and E. faecalis was isolated from 21 of the 33 culture positive teeth , 11 in pure culture . Growth was detected in 10 teeth of the second sample s. Six of the 10 cases were E. faecalis , with five being a pure culture . All third sample s ( after IKI ) except one were negative . The number of microbial cells per sample did not correlate with lesion size . Two flare-ups were recorded , both in teeth with a mixed infection . CONCLUSION The high prevalence of enteric bacteria and yeasts in root-filled teeth with chronic apical periodontitis was established . IKI improved the antimicrobial effect of the treatment Traditional clinical review articles , also known as up date s , differ from systematic review s and meta-analyses . Up date s selectively review the medical literature while discussing a topic broadly . Non-quantitative systematic review s comprehensively examine the medical literature , seeking to identify and synthesize all relevant information to formulate the best approach to diagnosis or treatment . Meta-analyses ( quantitative systematic review s ) seek to answer a focused clinical question , using rigorous statistical analysis of pooled research studies . This article presents guidelines for writing an evidence -based clinical review article for American Family Physician . First , the topic should be of common interest and relevance to family practice . Include a table of the continuing medical education objectives of the review . State how the literature search was done and include several sources of evidence -based review s , such as the Cochrane Collaboration , BMJ 's Clinical Evidence , or the InfoRetriever Web site . Where possible , use evidence based on clinical outcomes relating to morbidity , mortality , or quality of life , and studies of primary care population s. In articles su bmi tted to American Family Physician , rate the level of evidence for key recommendations according to the following scale : level A ( r and omized controlled trial [ RCT ] , meta- analysis ) ; level B ( other evidence ) ; level C ( consensus/expert opinion ) . Finally , provide a table of key summary points In many areas of medicine the amount of published information is increasing at an exponential rate , making it difficult for the clinician to condense the data to a manageable amount of valuable and useful information . Systematic review s have been suggested as a remedy for this information overload . Such review s are regarded as the highest level of evidence . Certain statistical methods , e.g. , meta- analysis , have also been introduced for the calculation of a more comprehensive summation of the compiled results from studies with small sample sizes . These findings would then serve as an authoritarian guide for evidence -based practice . Endodontists have lately jumped on the b and wagon of systematic review s and meta-analyses , and papers on various topics are being published . Well done , such comprehensive information would be very useful and authoritative for the practitioner . Alarmingly , the quality of these recent publications is negatively correlated to the frequency . This can have serious consequences in the clinical arena if spurious information is given a seal of approval when communicated as facts in refereed journals . A systematic literature review is design ed to focus on a single question and to synthesize all high- quality research reports relevant to the question . In these studies , however , sources of bias are often not controlled . Therefore , even the best review and meta- analysis becomes useless if it is based on poorly design ed research . Furthermore , these review s are mostly based on published data which are too often biased toward studies that show significant differences in results and /or outcome . “ Uninteresting ” conclusions tend not to be published . Endodontic literature , thus far , is short on well design ed and executed r and omized clinical trials . Furthermore , clinical protocol s often have many important “ proprietary ” modifications that make comparison difficult . This makes it very hard to undertake a systematic review to answer a narrow question . Such GIGO ( garbage in , garbage out ) can easily lead to biased conclusions and reinforce already existing biased comclusions . An example of such bias can be illustrated by a meta- analysis recently published . The study focused on assessing if there were differences in outcome between 1 and 2 treatment visits when treating teeth with apical periodontitis . Relevant publications on this topic are rare , and with the narrow inclusion criteria only 3 investigations were available for the review . However , the only factors connecting these 3 studies was the words “ single ” and “ two visits ” in the title . Beyond that , the selected studies are too different and inadequate for the study . Only 1 study is somewhat demonstrably r and omized , and outcome assessment s are based on 3 vastly different criteria . Two of the studies use calcium hydroxide as intracanal dressing , whereas the third uses no intervisit medication . Complexity of initial pathology and healing time are also clearly factors of great importance but not controlled . In addition , sample sizes in the component studies as well as the final cohort are all too small for the conclusions that there was no significant difference between 1or 2-visit treatment protocol s. To undertake and publish a meta- analysis on such an incomplete sample is counterproductive . Although the publication noted its numerous limitations , it will still communicate erroneous conclusions with a poor scientific foundation to the less informed reader . There are other examples of recently published systematic review s that are very ambiguous and tend to communicate spurious facts . One of these studies looks at the effect of smear-layer removal on sealing ability of root canal obturation . The study is entirely limited to laboratory experiments , with the majority of evaluations using dye leakage which is generally considered to be unreliable . This is an example of review ers lacking content expertise . The authors draw the conclusion , using defective review material , that removal of smear layer enhances the seal of the root filling . We may generally believe that this is the truth |
2,264 | 20,708,804 | Very large effect sizes were obtained in some of the CBT studies , indicating a broad suitability of CBT in the treatment of core symptoms of PTSD in adult refugees .
Empirical evidence also points to the possibility that the maladaptive traumatic reactions in refugees can take shape of more complex reactions than those strictly specified in the diagnostic category of PTSD .
Effectiveness of CBT treatments has as yet not been tested on the whole range of symptoms in these complex cases . | BACKGROUND Refugees with posttraumatic stress disorder ( PTSD ) often present with complicated traumatic symptoms , prolonged and repeated exposure to traumatic events , acculturation , and social problems .
A consensus about suitability of psychosocial treatments for refugees does not exist .
Never the less there is a need to review the state of knowledge about effective treatments for traumatized refugees , to help guide the practitioners in their choice of treatment methods . | Traumatic stress due to conflict and war causes major mental health problems in many re source -poor countries . The objective of this study was to examine whether trained lay counselors can carry out effective treatment of posttraumatic stress disorder ( PTSD ) in a refugee settlement . In a r and omized controlled dissemination trial in Ug and a with 277 Rw and an and Somalian refugees who were diagnosed with PTSD the authors investigated the effectiveness of psychotherapy administered by lay counselors . Strictly manualized narrative exposure therapy ( NET ) was compared with more flexible trauma counseling ( TC ) and a no-treatment monitoring group ( MG ) . Fewer participants ( 4 % ) dropped out of NET treatment than TC ( 21 % ) . Both active treatment groups were statistically and clinical ly superior to MG on PTSD symptoms and physical health but did not differ from each other . At follow-up , a PTSD diagnosis could not be established anymore in 70 % of NET and 65 % TC participants , whereas only 37 % in MG did not meet PTSD criteria anymore . Short-term psychotherapy carried out by lay counselors with limited training can be effective to treat war-related PTSD in a refugee settlement We examined the feasibility , acceptability , and therapeutic efficacy of a culturally adapted cognitive – behavior therapy ( CBT ) for twelve Vietnamese refugees with treatment-resistant posttraumatic stress disorder ( PTSD ) and panic attacks . These patients were treated in two separate cohorts of six with staggered onset of treatment . Repeated measures Group × Time ANOVAs and between-group comparisons indicated significant improvements , with large effect sizes ( Cohen 's d ) for all outcome measures : Harvard Trauma Question naire ( HTQ ; d=2.5 ) ; Anxiety Sensitivity Index ( ASI ; d=4.3 ) ; Hopkins Symptom Checklist-25 ( HSCL-25 ) , anxiety subscale ( d=2.2 ) ; and Hopkins Symptom Checklist-25 , depression subscale ( d=2.0 ) scores . Likewise , the severity of ( culturally related ) headache- and orthostasis-cued panic attacks improved significantly across Little is known about the usefulness of psychotherapeutic approaches for traumatized refugees who continue to live in dangerous conditions . Narrative exposure therapy ( NET ) is a short-term approach based on cognitive-behavioral therapy and testimony therapy . The efficacy of narrative exposure therapy was evaluated in a r and omized controlled trial . Sudanese refugees living in a Ug and an refugee settlement ( N = 43 ) who were diagnosed as suffering from posttraumatic stress disorder ( PTSD ) either received 4 sessions of NET , 4 sessions of supportive counseling ( SC ) , or psychoeducation ( PE ) completed in 1 session . One year after treatment , only 29 % of the NET participants but 79 % of the SC group and 80 % of the PE group still fulfilled PTSD criteria . These results indicate that NET is a promising approach for the treatment of PTSD for refugees living in unsafe conditions Concentration camp survivors from Bosnia-Herzegovina , now refugees in the Netherl and s , were given early outpatient treatment for posttraumatic stress disorder ( PTSD ) for 6 months . They were tested with the Watson Question naire before entering therapy , after 6 months and 3 years later when a structured interview design ed to obtain information on psychosocial status was administered . Data were analyzed with PCA-STAT 1.1 statistical package . The treatment was effective on a short-term basis with some long-term effects . Elderly people were no more vulnerable to the onset of PTSD than younger ones but were more resistant to therapy . Psychosocial factors had neither protective nor risk value for the development of PTSD in this group The present study was design ed to evaluate the effects on children ( age : M = 5.5 years ) in war-torn Bosnia and Herzegovina of a psychosocial intervention program consisting of weekly group meetings for mothers for 5 months . An additional aim was to investigate the children 's psychosocial functioning and the mental health of their mothers . Internally displaced mother-child dyads were r and omly assigned to an intervention group receiving psychosocial support and basic medical care ( n = 42 ) or to a control group receiving medical care only ( n = 45 ) . Participants took part in interviews and tests to provide information about war exposure , mental health , psychosocial functioning , intellectual abilities , and physical health . Results showed that although all participants were exposed to severe trauma , their manifestations of distress varied considerably . The intervention program had a positive effect on mothers ' mental health , children 's weight gain , and several measures of children 's psychosocial functioning and mental health , whereas there was no difference between the two groups on other measures . The findings have implication s for policy Rates of posttraumatic stress disorder ( PTSD ) are exceptionally high among asylum-seekers . Reportedly , stressors caused by the asylum procedure and psychological consequences of torture contribute to the maintenance of symptoms and interfere with treatment . In a pilot r and omized controlled trial , the authors examined the efficacy of trauma-focused treatment in 32 asylum-seekers with PTSD result ing from state-sponsored violence and other traumatic events . Narrative exposure therapy ( NET ) was compared with treatment as usual ( TAU ) , with a focus on stabilization and psychoactive medication . Six months after treatment , a significant reduction of posttraumatic stress symptoms was found in the NET participants but not in the TAU group . Although treatment gains were moderate , these results indicate that NET is a promising approach for the treatment of PTSD in asylum-seekers living in unstable conditions This article examines the ability of the panic attack – posttraumatic stress disorder ( PTSD ) model to predict how panic attacks are generated and how panic attacks worsen PTSD . The article does so by determining the validity of the panic attack – PTSD model in respect to one type of panic attack among traumatized Cambodian refugees : orthostatic panic ( OP ) attacks ( i.e. panic attacks generated by moving from lying or sitting to st and ing ) . Among Cambodian refugees attending a psychiatric clinic , the authors conducted two studies to explore the validity of the panic attack – PTSD model as applied to OP patients ( i.e. patients with at least one episode of OP in the previous month ) . In Study 1 , the panic attack – PTSD model accurately indicated how OP is seemingly generated : among OP patients ( N = 58 ) , orthostasis‐associated flashbacks and catastrophic cognitions predicted OP severity beyond a measure of anxious – depressive distress ( Symptom Checklist‐90‐R subscales ) , and OP severity significantly mediated the effect of anxious – depressive distress on Clinician‐Administered PTSD Scale severity . In Study 2 , as predicted by the panic attack – PTSD model , OP had a mediational role in respect to the effect of treatment on PTSD severity : among Cambodian refugees with PTSD and comorbid OP who participated in a cognitive behavioural therapy study ( N = 56 ) , improvement in PTSD severity was partially mediated by improvement in OP severity The present study investigated the efficacy of cognitive-behavior therapy ( CBT ) and exposure therapy ( E ) in the treatment of post-traumatic stress disorder ( PTSD ) in refugees . Sixteen out patients fulfilling the DSM-IV criteria for PTSD were r and omized to one of the two treatments . Assessor and self-report measures of PTSD-symptoms , generalized anxiety , depression , quality of life and cognitive schemas were administered before and after treatment , and at a 6-month follow-up . The patients were treated individually for 16 - 20 weekly sessions . The results showed that both treatments result ed in large improvements on all the measures , which were maintained at the follow-up . There was no difference between E and CBT on any measure . E and CBT led to a 48 and 53 % reduction on PTSD-symptoms , respectively , a 49 and 50 % reduction on generalized anxiety , and a 54 and 57 % reduction on depression . The results were maintained at the 6-month follow-up . The conclusion that can be drawn is that both E and CBT can be effective treatments for PTSD in refugees Based on the results of a r and omized controlled trial , we examined a model of the mechanisms of efficacy of culturally adapted cognitive‐behavior therapy ( CBT ) for Cambodian refugees with pharmacology‐resistant posttraumatic stress disorder ( PTSD ) and comordid orthostatic panic attacks ( PAs ) . Twelve patients were in the initial treatment condition , 12 in the delayed treatment condition . The patients r and omized to CBT had much greater improvement than patients in the waitlist condition on all psychometric measures and on one physiological measure — the systolic blood pressure response to orthostasis ( d = 1.31)—as evaluated by repeated‐ measures MANOVA and planned contrasts . After receiving CBT , the Delayed Treatment Group improved on all measures , including the systolic blood pressure response to orthostasis . The CBT treatment 's reduction of PTSD severity was significantly mediated by improvement in orthostatic panic and emotion regulation ability . The current study supports our model of the generation of PTSD in the Cambodian population , and suggests a key role of decreased vagal tone in the generation of orthostatic panic and PTSD in this population . It also suggests that vagal tone is involved in emotion regulation , and that both vagal tone and emotion regulation improve across treatment Cambodian refugees with posttraumatic stress disorder ( PTSD ) represent a cohort in severe need of treatment , but little information is available to guide treatment choices . We selected a sample of pharmacotherapy-refractory individuals to test the efficacy of combination treatment with sertraline and cognitive-behavior therapy ( CBT ) for treating PTSD . Participants in this pilot study were ten Khmer-speaking women who had been at a mean age of 22 - 26 years during the Pol Pot period ( 1975 - 1979 ) . These patients were r and omly assigned to either sertraline alone or combined treatment . We found that combined treatment offered additional benefit in the range of medium to large effect sizes for PTSD and associated symptoms . Our findings indicate that substantial gains can be achieved by adding CBT to pharmacotherapy for PTSD , and that a program of CBT emphasizing information , exposure , and cognitive-restructuring can be successfully modified for Khmer-speaking refugees |
2,265 | 19,594,913 | Most instruments had some evidence of construct validity , through associations with tests of cognitive function , health literacy , activities of daily living or measures of medication management or adherence .
Conclusion A number of performance-based instruments exist to assess patients ' capacity to manage their own medications . | Background Older people are commonly prescribed complex multi-drug regimens while also experiencing declines in the cognitive and physical abilities required for medication management , leading to increased risk of medication errors and need for assisted living .
The purpose of this study was to review published instruments design ed to assess patients ' capacity to self-administer medications . | BACKGROUND We tested the hypothesis that impairment in the ability to take medication independently predicts early functional decline . METHODS A 12-month , prospect i ve cohort study was performed at two continuing-care retirement facilities using the Drug Regimen Unassisted Grading Scale ( DRUGS ) . This geriatric screening tool utilizes a stepwise progression of four tasks : ( i ) identification , ( ii ) access . ( iii ) dosage , and ( iv ) timing . RESULTS Forty-seven ( 86 % ) of the eligible participants completed the 12-month follow-up assessment ; three were transferred to skilled nursing facilities . The mean age at study entry was 84.2+/-5.1 years ; 72 % of the participants were women , and 68 % were college educated . At 12 months there was a decline in the Mini-Mental State Examination ( MMSE ) score ( p = .029 ) , an increase in the timed " Up and Go " test ( p = .023 ) , and a decline in the DRUGS score ( p .029 ) . Nine ( 18 % ) of the participants resided in assisted- versus independent-living situations compared with three participants ( 5 % ) at study entry ( p = .031 ) . Both 12-month DRUGS score and 12-month self-reported medication management capacity were associated with 12-month MMSE ( p = .0001 and p = .019 , respectively ) . Baseline DRUGS score was associated with 12-month MMSE and Geriatric Depression Scale scores ( p = .0002 and p = .002 , respectively ) . Both baseline DRUGS score and self-reported medication management capacity were also associated with residence in assisted-living communities at 6 months ( p = .029 and p = .040 , respectively ) . MMSE was not associated with any of the clinical outcomes Abstract BACKGROUND : Patients ’ ability to manage medications is critical to chronic disease control . Also known as medication management capacity ( MMC ) , it includes the ability to correctly identify medications and describe how they should be taken . OBJECTIVE : To evaluate the effects of low literacy , medication regimen complexity , and sociodemographic characteristics on MMC . DESIGN : Cross-sectional analysis of enrollment data from participants in a r and omized trial . PARTICIPANTS : Patients with coronary heart disease in an inner-city clinic . MEASUREMENTS : Medication management capacity was measured with the Drug Regimen Unassisted Grading Scale ( DRUGS ) , which scores subjects ’ ability to identify , open , describe the dose , and describe the timing of their medications . DRUGS overall and component scores were compared by literacy . Mini Mental State Exam score , regimen complexity ( number of prescription medications ) , and sociodemographic characteristics . RESULTS : Most of the 152 participants were elderly ( mean age 65.4 years ) , women ( 54.6 % ) , and African American ( 94.1 % ) . Approximately half ( 50.7 % ) had inadequate literacy skills , and 28.9 % had marginal skills . In univariate analysis , MMC was significantly associated with literacy ( P<.001 ) , and this effect was driven by the ability to identify medications . In multivariable models , patients with inadequate literacy skills had 10 to 18 times the odds of being unable to identify all of their medications , compared with those with adequate literacy skills ( P<.05 ) . CONCLUSIONS : Adults with inadequate literacy skills have less ability to identify their medications . Techniques are needed to better educate low-literacy patients about their medications , as a potential strategy to enhance adherence OBJECTIVE To examine whether reduced ability to self-administer medication can accurately classify living placement ( independent or assisted living ) in a continuing care retirement community ( CCRC ) . DESIGN Convenience sample of consecutive patients seen in a medical clinic . SETTING An outpatient medical clinic at a CCRC . PARTICIPANTS A group of 78 consecutive patients ( aged 68 - 98 years ) scheduled for a geriatric medical evaluation between May 1 , 2001 , and August 31 , 2001 , residing in an independent ( IL ) or assisted living ( AL ) apartment . MEASUREMENTS Ability to self-administer medication was assessed by asking residents to respond to a medication administration question based on a 5-point Likert scale . Residents were also given measures of cognitive status ( MMSE ) , activities of daily living ( ADL ) , and depression ( GDS ) . Further , age of residents as well as number of falls within the previous 6 months were recorded . RESULTS A discriminant function analysis accurately classified living placement ( IL or AL ) in 89.7 % of the cases based on the ability of residents to self-administer medication . The additions of MMSE score , ADL performance , GDS score , number of falls , and age of the residents to the analyses did not improve the number of cases that were correctly classified . CONCLUSION Ability to self-administer medication emerged as the main predictor of current living environment within the CCRC in the present study . These results underscore the importance of considering a resident 's ability to independently manage his or her medications when placement decisions are being made within CCRCs Background : Consumer participation in planning and implementing health care is actively encouraged as a means of improving patient outcomes . In assessing the ability of patients to self-medicate , health professionals can identify areas in which patients need assistance , education , and intervention to optimize their health outcomes after discharge . Objective : To develop and vali date a tool to quantify the ability of patients to administer their regularly scheduled medications while they are hospitalized . Methods : Past research enabled us to develop the Self-Administration of Medication ( SAM ) tool . Using a Delphi technique of 3 rounds , a panel of expert health professionals established the content validity of the tool . For determining level of agreement in using the SAM tool , 56 patients were selected ; for each patient , 2 r and omly selected nurses completed an assessment . Construct validity and internal consistency were examined by testing the tool in 50 patients and comparing with other vali date d scales . Results : The 29-item SAM tool had high content validity scores for clarity , representation , and comprehensiveness , with content validity index values ranging from 0.95–1.0 . In testing the level of agreement between 2 nurses , out of 43 valid cases , 95.3 % of nurses overwhelmingly agreed about the patients ’ competence to self-administer their drugs . The intraclass correlation coefficient was 0.819 ( 95 % Cl 0.666 to 0.902 ) . Internal consistency for the SAM tool was high , with a Cronbach 's alpha of 0.899 . A moderate to strong correlation was obtained when comparing the SAM tool with other vali date d measures . Conclusions : The SAM tool is valid and reliable for quantifying patients ’ ability to manage their regularly scheduled medications in the hospital setting This study used performance tests to assess the cognitive , visual and physical abilities related to taking medicines in the elderly population . The study population consisted of the Swedish Panel Study of Living Conditions of the Oldest Old ( SWEOLD II ) , a nationally representative interview survey . SWEOLD II is a r and om sample of all community-based and institutionalized persons aged 77 + in Sweden . Five tests related to medication management were administered in the direct interviews ( n=492 ) : h and function ( opening bottle ) , vision ( reading label ) , and medication competence ( comprehension and calculation ) . Results showed that 9.4 % could not read instructions on a medicine container and 14.6 % had difficulty opening a plastic flip-top medicine bottle . The three cognitive tests related to taking medicine result ed in 30.7 , 47.4 and 20.1 % errors . Combining all the tests revealed that 66.3 % of the sample had at least one limitation of capacity related to taking medicine . There were no significant gender differences . Among those people who did not pass all the tests , 31.8 % lived alone with no home-help . Taking medicines is a complex task and a large proportion of the Swedish elderly population has cognitive , visual or physical limitations that may hinder their ability to take medicines accurately . Awareness of these limitations is essential to concordance OBJECTIVE To study the relationship between four cognitive screens ( Mini-Mental State Examination [ MMSE ] , Mini-Cog , Medication Transfer Screen [ MTS ] , and Medi-Cog [ Mini-Cog + MTS ] ) and pillbox concordance . DESIGN Prospect i ve cross-sectional pilot study . SETTING Primary care federal health care system . PARTICIPANTS English literate in patients not previously diagnosed or treated for dementia and without physical h and icap preventing use of a pillbox . MAIN OUTCOME MEASURE Correlation between cognitive screens and prospect i ve pill-count scores ( PPCS ) . INTERVENTIONS Mini-Cog , MTS , and MMSE screening was followed by a 28-compartment pillbox skills assessment . A passing PPCS was defined as correctly loading 80 % of the medications in the pillbox . A PPCS of < 80 % identified patients for pillbox-organization education or supportive intervention . Variables associated with total and passing PPCS were analyzed by multivariate linear and logistic regression , respectively . RESULTS Fifty-three patients discharged on > 1 medication completed all screenings . Other than cognitive screening , only age was associated with total and passing PPCS . After adjustment for age , Medi-Cog had the highest correlation with total PPCS [ r2=0.53 ; P<0.001 ) , whereas Mini-Cog was the single cognitive assessment that remained significantly associated with a passing PPCS ( r2=0.23 ; P=0.023 ) . Age-adjusted models , including MMSE , had relatively poor association with total PPCS ( r2=0.23 ; P=0.046 ) and no association with passing PPCS ( r2=0.15 ; P=0.46 ) . The Medi-Cog exhibited modest highest overall sensitivity ( 72 % ) and specificity ( 61 % ) to detect a passing PPCS . CONCLUSION MMSE is a relatively poor measure of the ability of patients to fill a pillbox . The Medi-Cog and Mini-Cog may have value for assessing pillbox concordance for patients who load their own pillboxes OBJECTIVES To assess relationships between vision ( contrast sensitivity , stereopsis , visual acuity ) and a performance-based measure of ability to implement new medications . DESIGN Cross-sectional analysis ; prospect i ve cohort study . SETTING Community-based . PARTICIPANTS Three hundred thirty-five participants aged 73 to 82 in Year 3 of the Women 's Health and Aging Study II , a representative sample of the two-thirds least-disabled community-dwelling women . MEASUREMENTS Hopkins Medication Schedule Pillbox Ratio , a joint measure of accuracy and time , and a performance-based measure of ability to implement a prescription . Participants received written and verbal instructions for taking two medications and were directed to place pills in a pillbox accordingly . Vision assessment s : contrast sensitivity ( Pelli-Robson letter sensitivity chart ) , stereopsis ( R and ot Circles ) , and visual acuity ( Early Treatment Diabetic Retinopathy Study eye chart ) . RESULTS Forty-four percent ( 148/335 ) of women incorrectly placed one or both medications . Each vision measure was positively associated with Pillbox Ratio scores and varied with cognition and time to completion . Better visual acuity , contrast sensitivity , and stereopsis were each associated with better performance in women with poor cognition who filled the pillbox quickly . Additionally , better visual acuity was associated with better performance in participants with good cognition who filled the pillbox slowly ; better stereopsis was associated with better performance in participants with poor cognition who filled the pillbox slowly and whose stereoacuity was below normal . CONCLUSION Visual acuity , contrast sensitivity , and stereopsis should be considered potential risk factors for impaired ability to implement a medication regimen in older adults . Future research should investigate the role of vision , including contrast sensitivity and stereopsis , on performance of other instrumental activities of daily living OBJECTIVES To clarify the association between unmet medication management need and 3-year mortality and hospitalization for community-dwelling older people with various levels of disabilities . DESIGN Prospect i ve cohort study ( the Nagoya Longitudinal Study for Frail Elderly ) . SETTING Community-based . PARTICIPANTS One thous and seven hundred seventy-two community-dwelling elderly subjects ( 611 men , 1,161 women ) . MEASUREMENTS Data included the clients ' demographic characteristics , a rating for basic and instrumental activities of daily living ( ADLs ) , number of prescribed medications and physician-diagnosed chronic diseases , medication adherence , ability to manage medication , and presence or absence of medication assistance . Cox proportional hazard models and the Kaplan-Meier method were used to assess the association between the medication management at baseline and mortality or hospitalization during a 3-year period . RESULTS Of 1,772 participants , 681 reported no difficulty with self-medication management , and 1,091 experienced difficulty with self-medication . Of participants with difficulty with self-medication management , 929 had medication assistance , and 162 did not . During a 3-year follow up , 424 participants died , and 758 were admitted to hospitals . The baseline data demonstrated that participants not receiving medication assistance were younger and had better ADL status and fewer comorbidities . Multivariate Cox regression models adjusting for potential confounders showed that the lack of assistance in those who needed medication assistance was associated with hospitalization but not mortality during the study period . CONCLUSION In community-dwelling disabled elderly people , lack of medication assistance in those needing medication support was associated with higher risk of hospitalization Objective : To review literature on instruments available for assessing the physical and cognitive ability to take medications as prescribed , which serve as a way to rule out reasons for nonadherence . Data Sources : A PubMed search ( 1950–February 2008 ) was conducted to identity relevant articles . Additional references were obtained from cross-referencing the bibliographies of selected articles . Only journals containing English- language articles were selected for review . Study Selection and Data Extraction : Articles that described a simulated assessment of medication management were obtained , irrespective of whether the assessment also contained data about medication adherence or was focused on older adults . Data Synthesis : Fifteen instruments were identified . Six instruments required 5 minutes or less to administer . 5 required 6–30 minutes , and 4 had no administration time data reported . A possible advantage of 3 of the instruments is that they use a subject 's own medications and may therefore provide a more authentic assessment . Only 2 instruments have been tested by subjects other than the drug developers and only one has been used in 2 different population s , thereby affording soma insight into generalizability . These studies have used a variety of other vali date d surveys/ assessment s to provide an indication of construct validity , including neuropsychological batteries , caregiver reports , prospect i ve outcomes , instrumental activities of daily living , and levels of care . One instrument determined whether Individuals could tell if refills existed , whom to contact , and re sources to obtain medications . Three assessed numeracy literacy . Conclusions : Five instruments that measure medication management capacity should be compared for potential further use , including Beckman 's tasks , due to their brevity and assessment of numeracy literacy ; the Medication Management Ability Assessment , Drug Regimen Unassisted Grading Scale , and Hopkins Medication Schedule because of the evidence supporting their use ; and the Medication Management Instrument for Deficiencies In the Elderly because it includes an assessment of the patient 's knowledge of how to obtain more medications . No brief tool is available for the primary care setting to identify individuals with medication management problems or to guide the type and amount of support required to manage medications |
2,266 | 22,385,731 | The E/N ratio is not a constant value but decreases continuously with increasing protein loss . | BACKGROUND & AIMS The ratio of energy expenditure to nitrogen loss respectively of energy to nitrogen provision ( E/N ) is considered a valuable tool in the creation of an enteral or parenteral formulation .
Specific E/N ratios for parenteral nutrition ( PN ) have not yet been clearly defined .
To determine the range of energy expenditure , nitrogen ( protein ) losses , and E/N ratios for various patient groups , we performed a systematic review of the literature . | OBJECTIVE To investigate whether protein intake influences the decline in energy expenditure during energy restriction . DESIGN Cross-over study of three diets of 4.2 MJ/d for 7 days : one diet with 36 % energy as protein and two with 15 % energy as protein , one high in carbohydrate and the other high in fat . SUBJECTS Two men and six women aged 31 - 57 y. BMI 27.B-34.1 kg/m2 . MEASUREMENTS 24-h energy expenditure ( 24-h EE ) , sleeping metabolic rate ( SMR ) and body weight on days 0 and 7 of each diet ; 24-h urinary nitrogen excretion ( 24-h UN ) on days 0 - 7 of each diet . RESULTS 24-h EE and SMR declined on all three diets but the decrease was significantly less on the high protein diet than on the two low protein diets . Weight loss was similar on all three diets . 24-h UN was less than N intake on the high protein diet but greater than N intake on the two low protein diets . CONCLUSIONS Maintaining protein intake reduces the decrease in energy expenditure during energy restriction We measured energy expenditure ( MREE ) and nitrogen excretion ( UUN ) in patients with severe head injury r and omized to early parenteral ( TPN , n = 21 ) or jejunal ( ENT , n = 27 ) feeding with identical formulations . The MREE rose to 2400 + /- 531 kcal/day in both groups and remained at 135 % + /- 26 % to 146 % + /- 42 % of predicted energy expenditure over 4 weeks . Nitrogen excretion peaked the second week at 33.4 + /- 10 ( TPN ) and 31.2 + /- 7.5 ( ENT ) g N/day . Both routes were equally effective at meeting nutritional goals ( 1.2 x MREE , 2.5 g protein/kg/day intake , stabilized albumin and transferrin levels ) . Infections were equally frequent : 1.86 episodes/TPN patient versus 1.89 episodes/ENT patient . While patient charges were much greater for TPN , the hospital costs were similar for TPN and ENT support regimens . These findings show that patients with head injuries are hypermetabolic for weeks , that only 27 % are capable of spontaneously eating nutritional requirements by discharge , and that either TPN or ENT support is equally effective when prescribed according to individual measurements of MREE and nitrogen excretion Metabolic effects of increasing nitrogen intake during total parenteral nutrition ( TPN ) were studied in nine septic patients . The patients were given 5 % dextrose ( D5W ) for 1 d. For the next 6 d they received total parenteral nutrition ( TPN ) , at 1.35 times resting energy expenditure ( REE ) , containing either 191 or 366 mg N/(kg.d ) Non-protein calories were divided equally between glucose and lipid emulsion . Three patients were studied on both diets ( n = 6 for each diet ) . On the high- but not the low-N diet were significant increases in protein oxidation , blood urea N , O2 consumption , and CO2 production . TPN normalized most plasma amino acid levels but intramuscular amino acids remained unchanged . Transient positive N balance occurred during days 1 - 3 on the high- but not the low-N intake ; on days 5 - 6 N balance did not differ significantly from zero on either diet and the improvement ( 165 mg N/[kg.d ] ) was the same for both diets The aim of the study was to assess the total energy expenditure ( TEE ) , resting energy expenditure ( REE ) and physical activity level ( PAL ) in home-living cachectic patients with advanced pancreatic cancer . The influence of an energy and protein dense oral supplement either enriched with or without the n-3 fatty acid eicosapentaenoic acid ( EPA ) and administered over an 8-week period was also determined . In total , 24 patients were studied at baseline . The total energy expenditure was measured using doubly labelled water and REE determined by indirect calorimetry . Patients were studied at baseline and then r and omised to either oral nutritional supplement . Measurements were repeated at 8 weeks . At baseline , REE was increased compared with predicted values for healthy individuals ( 1387(42 ) vs 1268(32 ) kcal day−1 , P=0.001 ) , but TEE ( 1732(82 ) vs 1903(48 ) kcal day−1 , P=0.023 ) and PAL ( 1.24(0.04 ) vs 1.50 ) were reduced . After 8 weeks , the REE , TEE and PAL of patients who received the control supplement did not change significantly . In contrast , although REE did not change , TEE and PAL increased significantly in those who received the n-3 ( EPA ) enriched supplement . In summary , patients with advanced pancreatic cancer were hypermetabolic . However , TEE was reduced and this was secondary to a reduction in physical activity . The control energy and protein dense oral supplement did not influence the physical activity component of TEE . In contrast , administration of the supplement enriched with EPA was associated with an increase in physical activity , which may reflect improved quality of life A prospect i ve trial was conducted in 20 surgical intensive care unit patients receiving mechanical ventilation to compare estimates of resting energy expenditure ( REE ) with the measured values . The 12 women and 8 men ( mean age 61.7±2.8 ( s.e.m . ) years ) underwent a full nutritional assessment before measurement of their REE by indirect calorimetry using the MGM II metabolic cart ( Utah Medical ) . Their REE was estimated by the Harris‐Benedict formula ( mean 1324±53 ( s.e.m . ) kcal/day ) as well as an empirical formula ( where empirical formula = 22 × body weight in kg ) ( 1370 ± 68 ( s.e.m . ) kcal/day ) . Results by either estimate were not statistically different from the measured resting energy expenditure ( MREE ) ( 1382±130 ( s.e.m . ) kcal/day ) , by one‐way analysis of variance . No multiplication factors were needed to relate the Harris–‐Benedict formula to MREE in this critically ill population and the estimate by the empirical formula was as good and simpler to perform . Although values by the Harris — Benedict formula and empirical formula correlated significantly with MREE ( P<0.05 ) the correlation coefficients were low : 0.48 and 0.45 respectively . Thus , mean estimates were excellent for the group but less predictive for the individual . Multiple linear regressions did reveal that body composition and metabolic stress were of greater predictive value , since an equation relating weight ( P<0.003 ) , sex ( P<0.003 ) , white blood cell count ( P < 0.003 ) and 24‐h urinary creatinine excretion ( P < 0.05 ) could predict 76 per cent of the variation ( r = 0.87 ) in the MREE with an overall significance of P = 0.0002 . Given the importance of matching energy intake to needs in many critically ill patients who are mechanically ventilated , accurate measurement of the REE is recommended now that instrumentation is equal to the task OBJECTIVES We measured the energy and protein needs in 50 sequential , critically ill , ventilated patients requiring continuous renal replacement therapy ( CRRT ) for renal failure by using indirect calorimetry and three sequential isocaloric protein-feeding regimes of 1.5 , 2.0 , and 2.5 g. kg(-1 ) . d(-1 ) . We also assessed the compliance of actual feeding with target feeding and correlated the predictive energy requirements of the formulae with the actual energy expenditure ( EE ) measured by indirect calorimetry . We also determined whether these feeding regimes affected patient outcome . METHODS The energy and protein needs of 50 consecutive , critically ill patients ( 31 male ; age 53.3 + /- 17.4 y ; Acute Physiology and Chronic Health Evaluation ( APACHE II ) score : 26.0 + /- 8.0 ; Acute Physiology and Chronic Health Evaluation score predicted risk of death : 50.0 + /- 25.0 % ) were assessed by using indirect calorimetry and ultrafiltrate nitrogen loss . Entry into this study was on commencement of CRRT . To eliminate any beneficial effect from the passage of time on nitrogen balance , 10 of the 50 patients were r and omized to receive 2.0 g. kg(-1 ) . d(-1 ) throughout the study , and the others received an escalating isocaloric feeding regime ( 1.5 , 2.0 , and 2.5 g. kg(-1 ) . d(-1 ) ) at 48-h intervals . Enteral feeding was preferred , but if this was not tolerated or unable to meet target , it was supplemented or replaced by a continuous infusion of total parenteral nutrition . Energy was given to meet caloric requirements as predicted by the Schofield equation corrected by stress factors or based on the metabolic cart readings of EE and was kept constant for all patients throughout the trial . Patients were stabilized on each feeding regime for at least 24 h before sample s of dialysate were taken for nitrogen analysis at 8-h intervals on the second day . CRRT was performed by using a blood pump with a blood flow of 100 to 175 mL/min . Dialysate was pumped in and out counter-currently to the blood flow at 2 L/h . A biocompatible polyacrylonitrile hemofilter was used in all cases . RESULTS EE was 2153 + /- 380 cal/d and increased by 56 + /- 24 cal/d ( P < 0.0001 ) throughout the 6-d study period to 2431 + /- 498 cal/d . At study entry , the mean predicted ( Schofield ) caloric requirement was 2101 + /- 410 . Patients received 99 % of the predicted energy requirements . However , the mean EE was 11 % higher at 2336 + /- 482 calories . This difference was not uniform . If the predicted caloric requirement was less than 2500 , the EE exceeded the predicted by an average of 19 % . If the predicted caloric requirement was greater than 2500 , the EE on average was 6 % less than predicted . This relation was significant ( P = 0.025 ) and has not been described previously . Nitrogen balance was inversely related to EE ( P = 0.05 ) , positively related to protein intake ( P = 0.0075 ) , and more likely to be attained with protein intakes larger than 2 g. kg(-1 ) . d(-1 ) ( P = 0.0001 ) . Nitrogen balance became positive in trial patients over time but were negative in control patients over time ( P = 0.0001 ) . Nitrogen balance was directly associated with hospital outcome ( P = 0.03 ) and intensive care unit outcome ( P = 0.02 ) . For every 1-g/d increase in nitrogen balance , the probability of survival increased by 21 % ( P = 0.03 ; odds ratio , 1.211 ; 95 % confidence limits , 1.017,1.443 ) . Further , although enterally and parenterally fed patients had lower mortalities than predicted , the presence of enteral feeding , even after adjusting for predicted risk of death , had a statistically significant benefit to patient outcome ( P = 0.04 ) . CONCLUSIONS This study found that a metabolic cart can improve the accuracy of energy provision and that a protein intake of 2.5 g. kg(-1 ) . d(-1 ) in these patients increases the likelihood of achieving a positive nitrogen balance and improving survival . Enteral feeding is preferable , but if this is not possible or does not achieve the target , then it should be supplemented by parenteral feeding The metabolic effects of TPN were studied in a selected group of trauma patients . Nineteen patients were r and omly divided into two groups : the first was treated with glucose and insulin , the second with glucose , insulin and amino acids . Each patient in both groups received TPN isocaloric with respect to daily energy output and the treatment lasted five days . Each group was further divided into two subsets ( severe or moderate catabolism ) according to fasting energy output with respect to the expected energy expenditure . During the acute flow phase , both in moderate as well as in severe catabolism , glucose and insulin were effective for protein sparing ; the maximum protein sparing effect was reached when giving a caloric intake equal to 130 % of daily energy output . Glucose , insulin and amino acids were effective in replacement of nitrogen losses . In moderately catabolic patients nitrogen balance was significantly better than in severely catabolic patients . This study shows that early and short-term TPN is effective in controlling the flow phase of trauma . Glucose and insulin appear to be the determinants of the protein sparing effect when given in amounts equal to those needed ; amino acids provided protein replacement when given in amounts equal to about 20 % of energy output . Energy supply higher than 120–130 % of daily energy output does not increase protein sparing and protein replacement , the only effect being a further increase in metabolism , which is possibly dangerous in critically ill patients The effects of increasing nitrogen intake were studied in 10 nutritionally depleted patients receiving total parenteral nutrition . After 1 to 2 days on 5 % dextrose , the patients received , in r and om order , intravenous diets containing either a low ( 180 mg/kg . day ) or high ( 364 mg/kg . day ) nitrogen content . Equicaloric amounts of glucose and fat emulsion were given . Total energy intake averaged 33.0 kcal/kg . day corresponding to 1.31 X resting energy expenditure or 1.08 X total energy expenditure . Nitrogen and energy balances were measured daily . Concentrations of glucose , glycerol , fatty acids , triglycerides , urea , insulin and glucagon in plasma , and of beta-hydroxybutyrate in whole blood were measured during the last 2 days of each diet period . An increase in plasma urea was the only change in hormone or substrate concentrations identified . Resting energy expenditure increased approximately 10 % , going from 5 % dextrose to the low and from the low to the high N diet . Nitrogen balances were 0.21 and 0.61 mg N/kg . day on the low and high N diets . Nitrogen retention of 21 % of the increment in intake , three times that seen in normal adult subjects , indicates that the malnourished patients in this study responded in a manner similar to growing organisms . Attainment of markedly positive N balance at , or close to , zero energy balance indicates that lean body mass can be restored without excessive energy intakes which may often be undesirable OBJECTIVE To determine whether medium-chain triglycerides , in low-to-moderate amounts consumed with meals ( at breakfast , lunch and dinner ) , can increase daily energy expenditure ( EE ) and 24-h urinary excretion of catecholamines in humans . DESIGN Dose-response study conducted under double-blind r and omised design . SETTING Respiratory chamber at the Faculty of Medicine , University of Geneva . SUBJECTS Eight healthy young men were recruited from the student population by advertisement in our Faculty . METHODS 24-h EE and urinary catecholamines were measured in each subject during stay in a respiratory chamber on four separate occasions . These were r and omised between four different combinations of medium-chain triglycerides ( MCT ) and long-chain triglycerides ( LCT ) , a total 30g/day , which was consumed with their habitual diet in three equal parts ( 10 g each ) at breakfast , lunch , and dinner in the following ratio of MCT : LCT ( g/g ) 0:30 , 5:25 , 15:15 and 30:0 . RESULTS 24-h EE increased significantly with increasing MCT : LCT ratio ( ANOVA , P < 0.001 ) , with the diet providing a total of 15 - 30 g MCT per day stimulating 24-h EE by 5 % : this corresponds to a mean absolute increase in daily EE of approximately 500kJ , with individual values varying between 268 kJ and 756 kJ. No significant differences were observed in respiratory quotient nor in urinary nitrogen losses across diets , but 24-h urinary noradrenaline was significantly increased ( ANOVA , P < 0.025 ) , whereas adrenaline and dopamine were unaltered . CONCLUSIONS This study suggests that relatively low-to-moderate intake of MCT ( 15 - 30 g per day ) as part of habitual diet may play a role in the control of human body composition by enhancing daily EE , and that this effect is mediated at least in part through activation of the sympathetic nervous system Objective : To quantify resting and total energy expenditure in patients who have suffered severe trauma and sepsis . Design : Prospect i ve , unblinded , observational , nonr and omized study . Setting : Critical care unit of a Level I adult trauma center . Patients : Immediate posttrauma patients or trauma patients exhibiting signs of sepsis with multiple organ dysfunction . Interventions : An indirect calorimeter was used to measure energy expenditure at rest ( resting energy expenditure ) at 0700 and 1900 hrs . The energy expenditure measurement was then continued for up to 12 hrs ( total energy expenditure ) . Clinical data were collected for computation of an illness severity score . Results : Thirteen trauma and 20 septic patients were studied 240 times . All patients were mechanically ventilated . Morphine or fentanyl was infused during 99 % of studies . Neuromuscular blocking agents were used in 42 % of septic studies . Both the trauma and septic groups were hypermetabolic ( mean trauma resting energy expenditure , 36 ± 6 kcal/kg ; mean septic resting energy expenditure , 44 ± 8 kcal/kg ; p < .05 ) . Total energy expenditure was similar to resting energy expenditure ( trauma total energy expenditure = resting energy expenditure × 1.035 ± 0.078 , septic total energy expenditure = resting energy expenditure × 1.039 ± 0.071 ) . Total energy expenditure and resting energy expenditure were linearly related ( r2 = .89 , p < .0001 ) . Conclusions : Trauma and septic patients are hypermetabolic , even when heavily se date d or medically paralyzed . A measurement of resting energy expenditure is a close approximation of total energy expenditure in most patients . ( Crit Care Med 1994 ; 22:1796–1804 Twenty-four subjects with burns ranging from 25 - 70 per cent received for 12 days exclusively per os a series of 4 isocaloric diets of about 4000 Kcal--'normal ' , or hyperproteic , or hyperlipidic , or hyperglucidic according to a r and omized schedule . Oxygen consumptions were measured at the end of each diet and nitrogen balance was determined every day . Though patients were not massively overfed there remained a positive energy gap . The nitrogen balance was found to be equilibrated on the whole but clearly positive with the hyperproteic diet and clearly negative with the hyperlipidic-normoproteic diet . Thus there is no rationale for the huge energy overfeeding classically used The effects of increasing glucose intake on nitrogen balance , energy expenditure and fuel utilization were measured in malnourished adult patients receiving parenteral nutrition with constant nitrogen intake and high or low glucose intakes for 8 day periods . Energy balance , nitrogen balance , weight and temperature were determined daily . Blood sample s taken at admission and at the end of days 7 and 8 of each diet were analysed for glucose , fatty acids , urea , insulin , glucagon and thyroid hormones . The effect of increasing glucose intake was to increase nitrogen balance by 0.28 + /- 0.08 ( SEM ) mg/kJ. A scheme is proposed , based on present and previous findings , of the separate effects of nitrogen and energy intake on nitrogen balance , permitting calculation of rates of repletion of fat and lean body mass from estimates of nitrogen intake and energy balance . Malnourished patients are shown to attain markedly positive nitrogen balances at zero or negative energy balances . Large errors in estimation of energy requirements have little effect on nitrogen balance . Changes in nitrogen balance were entirely due to changes in urea excretion . Creatinine excretion increased 12 % with high glucose intake , attributed mainly to increased muscle mass ( 7 % ) and body temperature ( 4 % ) . A 12 % increase in resting energy expenditure was only partly due to costs of glycogen storage and lipogenesis ; the remainder , about one-half , is probably due to glucose and insulin mediated increases in sympathetic activity . There were marked increases in 3,5,3'-triiodothyronine ( T3 ) concentrations with time , but no difference between the high and low glucose diets . The T3/thyroxine ratio , an index of free T3 concentration , increased much more rapidly on the high than on the low glucose diet . Changes in T3 could not account for the effect of glucose , under these conditions , to increase resting energy expenditure The purpose of this study was to examine the impact of nutritional support on nitrogen-energy relationships and functional parameters in malnourished patients with emphysema . Malnourished patients without lung disease served as the control group . Ten ambulatory , stable patients with emphysema and six patients without lung disease received an infusion of 5 % dextrose ( baseline ) plus electrolytes ( D5W ) for two days , which was followed by an enteral or a parenteral infusion of either a carbohydrate-based ( CB , 53 % carbohydrate ) or a fat-based diet ( FB , 55 % fat ) for 1 wk each , in a r and omized cross-over design . All patients had greater than 10 % weight loss . Caloric intake was set at 1.7 times the resting energy expenditure ( REE ) as measured during the baseline period . The REE of patients with emphysema was 23 and 27 % above that of the control group during baseline and refeeding periods , respectively . The increased REE was met primarily by an increased carbohydrate oxidation . During the infusion of D5W , N balance was lower in patients with emphysema , but during repletion N balance was similar in both groups of patients . Two weeks of nutritional support with either a CB or a FB diet increased body weight , N balance , and arm muscle area and improved maximal inspiratory pressure , skeletal muscle strength , and endurance-strength ( using quadriceps , hamstring , and h and grip ) to a similar degree in malnourished patients with and without lung disease . In other stress states , such as infection , it has been shown that hypermetabolism , hypercatabolism , and preferential fat oxidation occur concomitantly . Patients with emphysema are unusual because , although they are hypermetabolic , they are not hypercatabolic and do not demonstrate preferential fat oxidation To evaluate the effects of nutritional supplements on nitrogen and energy balances , body composition and immune parameters , HIV-infected malnourished adult out patients were prospect ively studied . Forty-six patients ( 4 females and 42 males ; 37 + /- 12 y ) were supplemented with a polymeric diet ( PD ) or regular foods ( RF ) on two consecutive 45-day periods on a crossover design . Weight , skinfold thicknesses , plasma albumin ( PA ) , CD4 and CD8 lymphocyte counts ( LC ) , resting energy expenditure ( REE ) and urinary nitrogen excretion were measured at baseline , 45 and 90-day . Food intake was weekly recorded by food surveys . Thirty-five patients completed the protocol ( 18 in Group 1:PD-->RF ; 17 in Group 2:RF-->PD ) . In both groups , weight , fat free mass ( FFM ) , energy balance ( EB ) and nitrogen balance ( NB ) increased significantly after PD , whereas LC and PA remained unchanged in both groups . The best results in terms of weight gain were obtained in the PD group and PD plus zidovudine subgroup ( n = 8) during the first 45 days ( weight gain/FFM gain : 4.8/2.6 kg and 6.8/3.1 kg , respectively ) . Nutritional supplement with PD , according to the EB and NB goals , was well tolerated and permitted to achieve a significant weight and FFM gain over a 90-day follow-up BACKGROUND We wanted to determine if achievement of energy balance decreases myofibrillar protein catabolism and nitrogen loss during posttraumatic catabolic illness . METHODS Surgical intensive care unit of a level I trauma center in a university medical center . Trauma patients expected to be mechanically ventilated for at least 4 days were r and omly assigned to one of three parenteral feeding groups : ( 1 ) nonprotein calorie group : dextrose and lipid intake equal to measured energy expenditure ; ( 2 ) total calorie group : dextrose , lipid , and protein intake equal to measured energy expenditure ; and ( 3 ) hypocaloric group : dextrose and lipid intake equal to 50 % of measured energy expenditure . Target protein intake for all groups was 1.7 g/kg body wt . On day 4 of nutrition support , a 24-hour balance study was conducted . Urine urea and total nitrogen production , 3-methylhistidine excretion , energy expenditure , and substrate utilization were measured . RESULTS Despite significant differences in nonprotein and total calorie balance among the groups , nitrogen loss , nitrogen balance , and catabolic rate were not significantly different . Nitrogen loss correlated with catabolic rate but not with energy expenditure or energy balance . Catabolic rate was associated with energy expenditure but not with energy balance . Nitrogen loss was positively correlated with the percentage of nonprotein energy expenditure met by nonprotein calorie intake . CONCLUSIONS Achievement of energy balance ( nonprotein or total energy ) failed to decrease catabolic rate or nitrogen loss acutely in multiple trauma patients . Provision of caloric intake equal to energy expenditure does not seem necessary during the acute phase of posttraumatic catabolic illness Severe head trauma patients ( HT ) exhibit markedly elevated energy expenditure and 24-hr urinary urea nitrogen excretion ( UUN ) values . The objective of this study was to compare seven spinal cord injured patients ( SCI ) to seven HT for changes in UUN and measured energy expenditure ( MEE ) over the first 18 days following injury . Energy expenditure was measured by indirect calorimetry and compared to values predicted by the Harris Benedict Equation ( PEE ) . There were six quadriplegics and one paraplegic in the SCI group . HT patients had peak Glasgow Coma Scale scores of 3 to 10 for the first 24 hr postinjury . Patients were studied prospect ively and matched for age , sex , and admitting weight Week 1 following the injury , SCI had mean UUN values of 0.18 + /- 0.04 g/kg/day vs 0.18 + /- 0.01 for HT patients . The mean MEE/PEE ratio was 0.56 for the SCI and 1.4 for HT ( p less than 0.01 ) . Over the entire study period the mean UUN value for SCI was 0.23 + /- 0.03 g/kg vs 0.21 + /- 0.01 for HT . The mean MEE/PEE ratio for SCI was 0.94 while HT remained elevated at 1.5 ( p less than 0.05 ) . Although the UUN was comparable in SCI vs HT , there was a significant difference in MEE/PEE between the groups . The elevation in UUN observed in SCI is not due to a hypermetabolic state . This suggests that different mechanisms promote the increased nitrogen excretion observed in these two population Obesity is a major health problem in the United States today . Traditionally , management of obese hospitalized patients has not differed from that of normal-weight patients , with calorie and protein needs based on current body weight and weight loss postponed until the acute illness has subsided . This study was undertaken to determine whether obese hospitalized patients ( > 130 % ideal body weight ) requiring total parenteral nutrition and given hypocaloric ( HC ) feedings with adequate protein intake could achieve nitrogen balance comparable with that of controls ( C ) given isonitrogenous normocaloric formulas . Sixteen obese patients ( HC = 9 , C = 7 ) were r and omized to either HC ( 50 % resting metabolic energy expenditure , plus protein ; calories : nitrogen = 75:1 ) or C ( 100 % resting metabolic energy expenditure , plus protein ; calories : nitrogen = 150:1 ) formulas . Resting metabolic energy expenditure was determined by indirect calorimetry on day 0 and weekly , and nitrogen balance was determined daily . The two groups were similar in Harris-Benedict predicted energy expenditure and metabolic energy expenditure , initial and final serum albumin , total iron-binding capacity , and weight loss . Total daily calorie and nonprotein calorie intake per kilogram body weight were 14 + /- 4.1 ( HC ) vs 25 + /- 4 ( C ) and 7 + /- 1.9 ( HC ) vs 20 + /- 3 ( C ) , respectively . Protein intake was 1.23 + /- 0.4 ( HC ) vs 1.31 + /- 0.2 ( C ) g/kg per day . Initial respiratory quotients were similar and consistent with fasting ( HC = 0.7 + /- 0.09 vs C = 0.66 + /- 0.09 ) ; final respiratory quotients in C patients reflected mixed fuel use ( C = 0.82 + /- 0.11 vs HC = 0.7 + /- 0.12 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Traumatized critically ill patients with either a moderate or severe catabolic response were studied . Patients were r and omly allocated to receive an intravenous solution which was either protein-free or contained protein and hypertonic glucose . The overall energy intake in both groups was equivalent to each patient 's daily requirement . In both the moderately catabolic and severely catabolic patients the urinary nitrogen loss with the protein-free solution was negatively correlated to the energy intake/energy need ratio ( p less than 0.01 , moderate catabolism ; p less than 0.001 , severe catabolism ) . The ratio of energy intake/energy need was correlated with the nitrogen loss . From the result ant straight line , the obligatory nitrogen loss was determined for those patients receiving the protein containing solution ( test diet ) . The net protein utilization was subsequently calculated using this value of the obligatory nitrogen loss . The net protein utilization was inversely correlated with the severity of trauma . It was significantly ( p less than 0.005 ) greater in the patients with a moderate catabolic response . In the acute postinjury phase , the net protein utilization of infused amino acids was similar to that for protein fed orally to normal healthy subjects BACKGROUND There is no consensus regarding the optimal duration of measurement or time of day to perform indirect calorimetry ( IC ) . Energy expenditure ( EE ) varies at different times of day and with different activity levels . We sought to assess the variability of EE in mechanically ventilated patients over a 24-hour period and the accuracy of 30-minute IC studies in predicting the 24-hour energy expenditure ( EE24 ) . METHODS The study was a prospect i ve comparison between the resting EE obtained by 30-minute measurement of IC and EE values obtained from 24-hour measurements . Tests were performed in the Medical Intensive Care Unit ( MICU ) of a tertiary care , university hospital . Oxygen consumption ( VO2 ) and carbon dioxide production ( VCO2 ) were measured for 24 hours in eight ventilated patients . Measurements were made every 3 minutes and used to calculate 30-minute and 24-hour oxygen consumption values . EE24 was calculated using the modified Weir equation . Each 30-minute interval was compared with the value obtained from the 24-hour measurement . RESULTS Three hundred forty-one of 384 30-minute intervals remained for analysis . Average EE24 measured was 1490 + /- 486 kcal/d . Average EE24 predicted by extrapolation from 30-minute studies was 1501 + /- 503 kcal/d , with a mean difference of 0 + /- 209 kcal/d from the measured 24-hour values ( range : -1068 to + 585 kcal/d ) . Thirty-minute studies were within 20 % of 24-hour measurements for 89 % of intervals . The difference between 24-hour and 30-minute studies correlated with changes in minute ventilation ( VE ) , heart rate , systolic blood pressure , and breath rate from their 24-hour means ( p < .001 ) . The mean error of EE estimate was greatest between 3 and 11 PM ( p < .001 ) . CONCLUSIONS We conclude the following : ( 1 ) EE in MICU patients is variable ; ( 2 ) 30-minute IC studies predict measured EE24 acceptably well for clinical purpose s ; and ( 3 ) accuracy is maximized if a 30-minute study is performed between 11 PM and 3 PM , and when Ve , heart rate , systolic blood pressure , and breath rate are near the day 's average |
2,267 | 24,722,980 | In conclusion , the available results from r and omized controlled trials do not support the hypothesis that physical training improves HRV in healthy children[AUQ2 ] | The positive effects of physical training on heart rate variability ( HRV ) in healthy adults are widely recognized ; however , the responsiveness to training in healthy children has not yet been established .
The aim of this study was to determine the influence of physical training on HRV in prepubertal healthy children . | ObjectOur objective was to investigate the effect of a long-term moderate exercise program on cardiac autonomic nervous system ( ANS ) activity in healthy children . Methods Three hundred and five children aged 6–11 years participated in a 12-month school-based exercise training program ( 130–140 bpm , 20 min/day , 5 days/week ) . Cardiac ANS activities were measured using heart rate variability ( HRV ) power spectral analysis in resting conditions . Following the first measurement , 100 children from the lowest total power ( TP ) HRV were chosen as experimental sample s and the same number of age- , height- , and weight-matched controls ( CG ) was r and omly selected from the remaining children . Results In the low group ( LG ) , all the frequency components of the HRV were significantly increased after the training period , whereas only low-frequency power was augmented in the control group ( CG ) . Conclusion Our data suggest that the 12-month moderate exercise training has a positive effect on cardiac ANS activity in the children who initially had low HRV Despite their extensive use , the reproducibility of cardiac autonomic measurements in children is not well-known . We investigated the reproducibility of short-term continuous measurements of heart rate ( HR ) , heart rate variability ( HRV , time and frequency domain ) , and spontaneous baroreflex sensitivity ( BRS , frequency domain ) in the supine and st and ing position in 57 children ( 11.2+/-0.7 years , 52.6 % boys ) . Reproducibility between two sessions within a two-week interval was evaluated by intraclass correlation coefficients ( ICCs ) , st and ard error of measurement , coefficients of variation ( CVs ) , limits of agreement , and Bl and -Altman plots . HR and HRV were moderately-to-highly ( ICC=.63-.79 ; CV=5.7%-9.7 % ) and BRS moderately ( ICC=.49-.63 ; CV=11.4%-14.0 % ) reproducible . While the BRS measurements were slightly less reproducible than the HR and HRV measurements , all can be reliably applied in research , thus implicating sufficient capacity to detect real differences between children . Still , clinical studies focusing on individual changes in cardiac autonomic functioning need to address the considerable r and om variations that may occur between test-retest measurements The aim of the present investigation was to compare the accuracy of the heart-rate ( HR ) deflection point ( HRDP ) and the second HR variability threshold ( HRVTh2 ) to predict anaerobic threshold in boys . HRDP was determined from slope trends of successive linear regressions . HRVTh2 was determined from the high frequency 's peak and power-density trends . The second ventilatory threshold ( VTh2 ) corresponding to the first decrease in PETCO2 , with an increase in VE /VCO2 , was used as the reference measure of AnT. Results show that VO2 and HR were similar at HRDP , HRVTh2 , and VTh2 . HRVTh2 and HRDP were highly correlated . It appears that HRVTh2 is a good alternative to HRDP for assessing anaerobic threshold . HRVTh2 and HRDP might rely on similar mechanisms Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials Objectives : To investigate the reliability of heart rate variability ( HRV ) measures at rest and during light exercise in children . Methods : Short term ( five minute ) HRV was assessed in 12 children ( 11–12 years of age ) . HRV measures were collected at rest with the children supine , breathing at 12 breaths/min , and during exercise on a cycle ergometer while exercising at 25 % of peak oxygen uptake . Both resting and exercise data were collected twice from each child . Results : Intraclass correlation coefficients were low to moderate for most measures with wide confidence intervals for each variable in both resting and exercise conditions . R and om variation ( typical error ) within repeated measurements ranged from 31 % to 187 % . Conclusions : These preliminary findings suggest that HRV measures are unreliable at rest and during light exercise in children aged 11–12 years . Tighter control of extraneous influences is recommended Aging results in marked abnormalities of cardiovascular regulation . Regular exercise can improve many of these age-related abnormalities . However , it remains unclear how much exercise is optimal to achieve this improvement or whether the elderly can ever improve autonomic control by exercise training to a degree similar to that observed in healthy young individuals . Ten healthy sedentary seniors [ 71 + /- 3 ( SD ) yr ] trained for 12 mo ; training involved progressive increases in volume and intensity . Static hemodynamics were measured , and R-wave-R-wave interval ( RRI ) , beat-to-beat blood pressure ( BP ) variability , and transfer function gain between systolic BP and RRI were calculated at baseline and every 3 mo during training . Data were compared with those obtained in 12 Masters athletes ( 68 + /- 3 yr ) and 11 healthy sedentary young individuals ( 29 + /- 6 yr ) at baseline . Additionally , the adaptation of these variables after completion of identical training loads was compared between the seniors and the young . Indexes of RRI variability and baroreflex gain were decreased in the sedentary seniors but preserved in the Masters athletes compared with the young at baseline . With training in the seniors , baroreflex gain and resting BP showed a peak adaptation after moderate doses of training following 3 - 6 mo . Indexes of RRI variability continued to improve with increasing doses of training and increased to the same magnitude as the young at baseline after heavy doses of training for 12 mo ; however , baroreflex gain never achieved values equivalent to the young at baseline , even after a year of training . The magnitude of the adaptation of these variables to identical training loads was similar ( no interaction effects of age x training ) between the seniors and the young . Thus RRI variability in seniors improves with increasing " dose " of exercise over 1 yr of training . In contrast , more moderate doses of training for 3 - 6 mo may optimally improve baroreflex sensitivity , associated with a modest hypotensive effect ; however , higher doses of training do not lead to greater enhancement of these changes . Seniors retain a similar degree of " trainability " as young subjects for cardiac autonomic function to dynamic exercise The risk of sudden death is increased in athletes with a male predominance . Regular physical activity increases vagal tone , and may protect against exercise-induced ventricular arrhythmias . We investigated training-related modulations of the autonomic nervous system in female and male endurance athletes . Runners of a 10-mile race were invited . Of 873 applicants , 68 female and 70 male athletes were r and omly selected and stratified according to their average weekly training hours in a low ( ≤4 h ) and high ( > 4 h ) volume training group . Analysis of heart rate variability was performed over 24 h. Spectral components ( high frequency [ HF ] and low frequency [ LF ] power in normalized units ) were analyzed for hourly 5 min segments and averaged for day- and nighttime . One hundred and fourteen athletes ( 50 % female , mean age 42 ± 7 years ) were included . No significant gender difference was observed for training volume and 10-mile race time . Over the 24-h period , female athletes exhibited a higher HF and lower LF power for each hourly time-point . Female gender and endurance training hours were independent predictors of a higher HF and lower LF power . In female athletes , higher training hours were associated with a higher HF and lower LF power during nighttime . In male athletes , the same was true during daytime . In conclusion , female and male athletes showed a different circadian pattern of the training-related increase in markers of vagal tone . For a comparable amount of training volume , female athletes maintained their higher markers of vagal tone , possibly indicating a superior protection against exercise-induced ventricular arrhythmias OBJECTIVE The beat-to-beat variability in electrocardiogram intervals ( RR , i.e. , heart-period variability ) provides information on cardiac autonomic activity that predicts arrhythmias and mortality rate in animals and adults . We determined the effect of physical training on heart-period variability in obese children . METHODS Thirty-five subjects were r and omly assigned to physical training and control groups . The training involved 4 months of exercise , 5 days per week , 40 minutes per day . Cardiovascular fitness was measured with submaximal heart rate during supine cycling ; percentage of body fat was measured with dual-energy absorptiometry ; and resting heart-period variability parameters were measured in a supine position . A pretraining to posttraining change score was computed for each variable . The effect of the training was determined by comparing the changes of the training and control groups . RESULTS Compared with the control group , the trained group ( 1 ) reduced submaximal heart rate and percentage of body fat ( p < 0.01 ) ; ( 2 ) increased in the root mean square of successive differences , a time-domain parameter reflective of vagal tone ( p < 0.05 ) ; ( 3 ) decreased in low-frequency power expressed as a percentage of total power , a frequency-domain index of combined sympathetic and vagal activity ( p < 0.03 ) ; and ( 4 ) decreased in the ratio of low- to high-frequency power , an index of sympathetic-parasympathetic balance ( p < 0.01 ) . CONCLUSIONS In obese children , physical training alters cardiac autonomic function favorably by reducing the ratio of sympathetic to parasympathetic activity OBJECTIVE Heart rate variability provides non-invasive information about cardiac parasympathetic activity ( PSA ) . We determined in obese children : ( 1 ) relations of baseline PSA to body composition and hemodynamics ; ( 2 ) effects of physical training ( PT ) and cessation of PT ; and ( 3 ) which factors explained individual differences in responsivity of PSA to the PT . RESEARCH METHODS AND PROCEDURES The root mean square of successive differences ( RMSSD ) was the index of PSA . Obese children ( n = 79 ) were r and omly assigned to groups that participated in PT during the first or second 4-month periods of the study . RESULTS Baseline RMSSD was significantly ( p<0.05 ) associated with lower levels of : fat mass , fat-free mass , subcutaneous abdominal adipose tissue , resting heart rate ( HR ) , resting systolic blood pressure , and exercise HR . Stepwise multiple regression produced a final model ( R2 = 0.36 ) that included only resting HR . The analysis of changes over the three time points of the study found a significant ( p = 0.026 ) time by group interaction , such that RMSSD increased during periods of PT and decreased following cessation of PT . Greater individual increases in response to the PT ( p<0.05 ) were seen in those who had lower pre-PT RMSSD levels , showed the greatest decreases in resting HR , and increased most in vigorous physical activity . The final regression model retained only the change in resting HR as a significant predictor of the changes in the RMSSD ( R2 = 0.23 ) . DISCUSSION Regular exercise that improved fitness and body composition had a favorable effect on PSA in obese children The aim of this study was to determine the influence of breathing frequency and tidal volume on resting heart rate variability in children aged 9 years ( n = 29 ) and 16 years ( n = 19 ) . Heart rate variability was measured in four conditions : ( 1 ) without the control of ventilation followed at r and om by ( 2 ) a fixed breathing frequency of 12 breaths · min -1 , ( 3 ) a breathing frequency of 12 breaths · min -1 but with a fixed tidal volume of 30 % vital capacity and ( 4 ) a fixed breathing frequency of 6 breaths·min -1 and a tidal volume of 30 % vital capacity . A total of 128 RR intervals ( the time between two spikes in the heart rate ) were detected and absolute high- and low-frequency spectral components were calculated using autoregressive modelling . The younger children were unable to control ventilation to achieve conditions 3 and 4 ; therefore , a 2 2 2 ( group 2 condition ) analysis of variance was used to analyse conditions 1 and 2 . There were significant interactions between group and heart rate variability conditions for the low-frequency component and the ratio of low to high frequencies ( P ≪ 0.001 ) . The main effect for condition showed that at 12 breaths · min -1 with no fixed tidal volume there was a significantly higher st and ard deviation of the RR interval , total power and high-frequency ( P ≪ 0.01 ) and lowfrequency spectral components ( P ≪ 0.05 ) than in the condition with no ventilatory control . Across the four breathing conditions for the older participants , the high-frequency spectral component was significantly higher in the condition at 6 breaths · min -1 with a fixed tidal volume than in that with no ventilatory control ( P ≪ 0.005 ) ; the ratio of high to low frequencies was significantly lower for the spontaneous condition than those performed at 12 breaths · min -1 ( P ≪ 0.001 ) . The results provide evidence of the need for ventilatory control when assessing short-term resting heart rate variability in children Heart rate variability , as determined from 24-hour Holter recordings , represents a noninvasive parameter for study ing the autonomic control of the heart . It decreases with certain disease states characterized by autonomic dysfunction such as congestive heart failure . No study in healthy or cardiac children has been performed to determine the correlations between and within time and frequency domain indices of heart rate variability . We examined five time domain ( SDNN , SDNNi , SDANNi , rMSSD and pNN50 ) and five frequency domain measures ( ULF , VLF , LF , HF and balance LF/HF ) in 200 healthy children and 200 children with congenital heart disease , aged 3 days to 14 years . All measures were significantly correlated with each other . However , the strength of correlation varied greatly . Our data show that variables strongly dependent on vagal tone ( rMSSD , pNN50 and HF ) were highly correlated ( r value > 0.90 ) , as well as SDNN and SDANNi . We conclude that certain time and frequency domain indices correlate so strongly with each other that they can act as surrogates for each other |
2,268 | 17,131,335 | The evidence does not support a protective effect of the use of sunbeds against damage to the skin from subsequent sun exposure . | Exposure to solar ultraviolet ( UV ) radiation is a known cause of skin cancer . | BACKGROUND Although sun exposure is an established cause of cutaneous malignant melanoma , possible interactions with host factors remain incompletely understood . Here we report the first results from a large prospect i ve cohort study of pigmentation factors and sun exposure in relation to melanoma risk . METHODS The Women 's Lifestyle and Health Cohort Study included 106 379 women from Norway and Sweden who were aged 30 - 50 years in 1991 or 1992 when they completed an extensive question naire on personal characteristics and exposures . Linkages to national registries ensured complete follow-up through December 31 , 1999 . Poisson regression models were used to estimate relative risks ( RRs ) . All statistical tests were two-sided . RESULTS During an average follow-up of 8.1 years , 187 cases of melanoma were diagnosed . Risk of melanoma was statistically significantly associated with increasing body surface area ( RR for > or = 1.79 m2 versus < or = 1.61 m2 = 1.60 , 95 % confidence interval [ CI ] = 1.03 to 2.48 ; P(trend ) = .02 ) , number of large asymmetric nevi on the legs ( RR for > or = 7 nevi versus 0 nevi = 5.29 , 95 % CI = 2.33 to 12.01 ; P(trend)<.001 ) , hair color ( RR for red versus dark brown or black = 4.05 , 95 % CI = 2.11 to 7.76 ; P(trend)<.001 ) , sunburns per year at ages 10 - 19 , 20 - 29 , and 30 - 39 years ( P(trend)<.001 , P(trend ) = .03 , and P(trend ) = .05 , respectively ) , and use of a device that emits artificial light ( solarium ) one or more times per month ( P = .04 ) . CONCLUSIONS Our results confirm previous findings that hair color , number of nevi on the legs , and history of sunburn are risk factors for melanoma and suggest that use of a solarium is also associated with melanoma risk . Adolescence and early adulthood appear to be among the most sensitive age periods for the effects of sunburn and solarium use on melanoma risk . However , it may be too early to see the full effect of adult exposures in this cohort Background : The incidence of skin cancer , the most common type of cancer in the Western world , has been shown to be associated with the degree of exposure to solar radiation . However , little is known on how human skin can be protected against UV-induced DNA damage by constitutive and induced pigmentation . Objective : To study the effect of skin pigmentation induced by a sunbed-type of treatment on the formation of UV-induced DNA damage in human skin in situ . Methods : A photoproduct assay was performed in untanned and tanned skin of healthy volunteers . Results : There is no significant difference in the induction of photoproducts between untanned and tanned skin . Conclusion : Our data demonstrate that constitutive skin pigmentation is more efficient than the induced one in protection against formation of photoproducts The incidence of cutaneous malignant melanoma ( melanoma ) and of basal cell carcinoma is still increasing in most fair-skinned population s. The fashion of intermittent exposure to solar ultraviolet ( UV ) radiations is considered the main cause of this increase . In 20 years time , tan acquisition through exposure to artificial sources of UV radiations has become frequent among fair-skinned adolescents and young adults . Modern sunbeds are powerful sources of UV radiations that do not exist in the nature , and repeated exposures to high doses of UVA constitute a new phenomenon in humans . A large prospect i ve cohort study on 106,379 Norwegian and Swedish women conducted between 1991 and 1999 has provided evidence for a significant , moderate increase in melanoma risk among regular sunbed users . Failure of past case-control studies to document with consistency the sunbed-melanoma association was probably due to a too short latency period between sunbed use and melanoma diagnosis , and to too few subjects with high total duration s of sunbed use . Regulations of sunbed installation , operation and use should become st and ardised across the 25 European Union countries . Enforcement of regulations in tanning parlours remains inadequate . In contrast , the existence of regulations is presented by many tanning salon operators as a guarantee that sunbed use is safe . We stress the need for the control of information disseminated by the " tanning industry " on suppositions that sunbed use is safer than sun exposure , and on the hypothetical health benefits of tanning . New fluorescent UV lamps are proposed that have a spectrum similar to the midday sun . Given the known association between intermittent sun exposure and melanoma , public-health authorities should reconsider the soundness of the commercialisation of these lamps BACKGROUND Indoor tanning is a popular behavior that may increase skin cancer risk . OBJECTIVE To examine characteristics associated with use or intention to use indoor tanning among adolescents . METHODS A telephone interview was conducted with 1273 adolescents , aged 14 to 17 years , in the Minneapolis-St Paul , Minn , and Boston , Mass , metropolitan areas . Questions included demographic and phenotypic characteristics , knowledge , attitudes , social factors , use of indoor tanning , and intention to tan indoors . RESULTS Twelve percent of boys and 42 % of girls had tanned indoors . Among nontanners , 22.4 % planned to start , and 77.2 % of tanners planned to continue tanning indoors . Nontanners and tanners at risk for future indoor tanning use were each significantly more likely to be female , less likely to use sun protection , less knowledgeable about skin cancer risks , more likely to agree that tans were attractive , and more strongly influenced by social factors compared with their low-risk counterparts . CONCLUSIONS Our data suggest that intention to tan indoors may identify a group of adolescents at risk for adopting the behavior ; prospect i ve studies are needed for confirmation BACKGROUND The relationship between cutaneous malignant melanoma and sunlamp use is examined in a Caucasian population in Connecticut , United States . METHODS Cases were diagnosed between 15 January 1987 and 15 May 1987 with a first primary cutaneous melanoma . Controls were obtained from the general population , frequency matched to cases by sex and age , through r and om digit dialling of Connecticut telephone numbers . RESULTS Of all study subjects , 141 ( 23 % ) cases and 95 ( 19 % ) controls reported ever having used sunlamps . The crude odds ratio ( OR ) for developing malignant melanoma after ever having used sunlamps was 1.30 ( 95 % confidence interval [ CI ] : 0.97 - 1.74 ) . This was reduced to 1.13 ( 95 % CI : 0.82 - 1.54 ) after further adjusting for cutaneous phenotype and recreational sun exposure . Those who used more than one type of sunlamp had a threefold higher risk for melanoma compared to never users . Subgroup analyses showed that sunlamp use was associated with a greater increase in risk for melanoma among those who used sunlamps at home and those who were first exposed to sunlamps prior to 1971 . The first use of sunlamps before the age of 25 showed somewhat higher risk for melanoma compared to first use later in life . CONCLUSION The current study provides limited evidence that use of sunlamps increases the risk of melanoma . For future studies , it is crucial that type of sunlamp , year of first use and amount of exposure are all taken into account . The association between melanoma and tanning with both UV-A and UV-B lamps and tanning under sunlamps early in life merits further investigation BACKGROUND The US Food and Drug Administration ( FDA ) recommends exposure limits for tanning bed use . Tanning patrons may not be following these recommendations and may be overexposed to damaging ultraviolet radiation ( UV ) . OBJECTIVE This study was conducted to assess tanning patrons ' adherence to FDA -recommended exposure limits and to measure the amount of UVA and UVB radiation emitted by tanning beds . METHODS A community-based survey was administered during routine state inspections of North Carolina tanning facilities ( n = 50 ) . At each facility , patron records were r and omly selected ( n = 483 ) for a survey of exposure records , and UVA and UVB outputs were measured for each tanning bed . RESULTS The recommended limits were exceeded by 95 % of patrons , and 33 % of patrons began tanning at the maximum doses recommended for maintenance tanning . Average tanning bed output was 192.1 W/m(2 ) UVA and 0.35 W/m(2 ) erythemally weighted UVB . CONCLUSIONS Interventions for tanning bed operators and patrons are needed to increase compliance with federally recommended exposure limits Summary Sunbed use was studied in relation to phenotype , erythema , sunscreen use and skin disease . The study population comprised 14–19 year‐old Stockholm adolescents in 60 r and omly selected classes , with 1252 students providing information . More than half ( 57 % ) reported sunbed use ± 4 times during the previous year . Skin type III dominated ( 64 % ) . Excessive exposure ( ± 10 times/year ) was not correlated to skin type . Sunscreens were most commonly used by sunbed users . Of all sunbed users , 44 % reported erythema . Adolescents with acne/seborrhoea , eczema or psoriasis used sunbeds more than others without skin diseases . The proportion with sunbed erythema ( 44 % ) indicates an unrecognized susceptibility to artificial ultraviolet radiation ( UVR ) among adolescents . The association between high exposure to UVR and sunscreen use stresses the importance of sunscreens being used as supplementary protection , not as a tool for tanning BACKGROUND The prevalence rates of both skin cancers and indoor tanning among the US population are high and have increased substantially in recent years . Low compliance by indoor tanning facilities with safety regulations may place consumers at greater risk of skin and ocular damage . OBJECTIVE This study quantified the level of compliance by indoor tanning facilities with selected federal and state regulations and recommendations . METHODS Tanning facilities ( N = 54 ) in San Diego County , California , were visited by a confederate posing as a prospect i ve customer . Compliance with 13 regulations/ recommendations were assessed by either direct query or observation of the presence/absence of signs and warning labels . Operators ' responses to 5 risk-based questions also were noted . RESULTS No facility complied with all 13 regulations/ recommendations . Compliance with 3 protective eyewear regulations was high ( 89%-100 % ) . In contrast , compliance with maximum tanning frequency recommendations ( approximately 6 % ) and parental consent regulations ( approximately 43 % ) was disturbingly low . CONCLUSION The investigators recommend instituting m and atory , comprehensive training for operators , as well as systematic compliance monitoring with enforcement of penalties for noncompliance The effects on 31 normal subjects following exposure to sunbeds containing UVA lamps with minimal UVB emission have been compared in a double‐blind study with the effects on nine control subjects of a similar exposure course three times weekly for 4 weeks to sunbeds emitting visible light . On previously untanned areas , all those subjects on active treatment developed a mild tan ; in tanned areas they all developed a moderate tan , while all control subjects developed a minimal to mild tan . The mean protection factor against later UVB‐induced erythema was 3.2±0.3 after the active course and 1.6±0.2 among the controls . Significantlsy more frequent adverse cutaneous effects for active subjects were pruritus , erythema , freckling , burning sensation , dryness and polymorphic light eruption . Cutaneous Langerhans cell numbers , and blood CD3 + ( pan T‐cell ) and CD4 + ( helper T‐cell ) lymphocyte subsets were reduced in both active and control groups . CD8 + ( cytotoxic/suppressor T‐cell ) counts were significantly reduced in both groups . The changes found in both groups seem attributable to small amounts of UVB emission from both active and control lamps UVA- and UVB-induced tans which were visually identical with each other were induced in separate sites on the lower back of 5 normal human volunteers of good tanning ability . Tanning was achieved by 4 exposures to UVA and UVB administered over an 8-day period . One week after the last exposure the protection afforded by the two types of tan against UVB-induced erythema and against UVB-induced DNA damage was measured . Protection against erythema was measured by comparison of the minimal erythema doses of UVB in tanned and untanned skin . Protection against DNA damage was assessed by comparing the numbers of endonuclease-sensitive sites in epidermal DNA extracted from biopsies taken from tanned and untanned sites exposed to the same dose of UVB . The UVB tans conferred significant protection ( mean 2.98-fold ) against UVB-induced erythema . UVA tans were not associated with significant protection ( mean 1.4-fold ) . In contrast , both UVA- and UVB-induced tans were associated with a similar reduction in yield of endonuclease-sensitive sites in epidermal DNA ( in UVA tan to 47 % and in UVB tan to 45 % of the yield in untanned skin ) . Protection conferred by the tans against erythema was therefore not paralleled by protection against DNA damage |
2,269 | 23,450,614 | Health service utilisation , such as rate of hospitalisation and general practice and emergency room visits , was also found to be reduced by the patient targeted pharmacist-provided services .
Pharmacist-provided services that target patients may improve clinical outcomes such as management of high glucose levels among diabetic patients , management of blood pressure and cholesterol levels and may improve the quality of life of patients with chronic conditions such as diabetes , hypertension and asthma .
Pharmacist services may reduce health service utilisation such as visits to general practitioners and hospitalisation rates . | BACKGROUND The role of pharmacists has exp and ed beyond dispensing and packaging over the past two decades , and now includes ensuring rational use of drugs , improving clinical outcomes and promoting health status by working with the public and other healthcare professionals .
OBJECTIVES To examine the effect of pharmacist-provided non-dispensing services on patient outcomes , health service utilisation and costs in low- and middle-income countries . | Malaria accounts for over 40 % of all outpatient consultations in Ghana . A common drug use problem associated with its treatment with chloroquine is over- and under-dosage and a preference for the intramuscular route of administration . Inadequate treatment is an important factor in the selection of resistant strains of malaria parasites . To ensure the proper management of diseases at health centres the Ministry of Health instituted an in-service training programme for medical assistants in 1987 . We evaluated the effect of this training on the clinical management of malaria using a quasi-experimental design . Three methods of data collection were used ; prescription survey , assessment question naires and focus group discussion s. Our findings revealed that gains in knowledge following the training had deteriorated within a year . There was also a discrepancy between knowledge and practice of malaria treatment . This was shown by over- and under-dosing of chloroquine in children and adults respectively . There was also overwhelming preference ( 85 % of all cases ) for injections and a high tendency towards polypharmacy ( average of five drugs per visit ) . The motivating reasons for these were mainly socio-cultural and included patient dem and and attitudes , prescriber self interests and stereotypes and the daily practical challenges of the community . While paying greater attention to supervision of clinical work at health posts , consideration must be given to socio-cultural context of drug use in any such future training programmes if rational use of drugs is to be achieved Objective Diabetes mellitus is a serious health problem associated with an increased mortality and morbidity . The association of improved glycemic control with sustained decrease in the rate of complications has been shown in r and omized clinical trials . Pharmaceutical care is a relatively new concept in Turkey ; yet , there are no recorded routine pharmaceutical care programs . Therefore , we aim ed to assess the impact of a short pharmaceutical care program conducted in the community pharmacy setting , on the indices of diabetes care of type 2 diabetic patients , particularly those regarding glycemic control and high blood pressure management . Setting The study was carried out at eight community pharmacies in Pendik district of Istanbul . Method All patients who visited any of the eight pharmacies through the pre-determined 1-week period were question ed for the presence of type 2 diabetes . Patients who reported to be type 2 diabetic ( n = 67 ) were informed about the study and invited to involve . During this prospect i ve longitudinal study , pharmaceutical care was provided to the patients by the same clinical pharmacist . The 3 month pharmaceutical care period consisted of six pharmacy visits . Main outcome measure : The main outcome measures were the improvement in glycemic control and blood pressure control ; while , weight control , self-monitoring of blood glucose , compliance and being under physician-control were also assessed . Results The study was conducted on 43 patients who accepted to involve . Fasting blood glucose was lowered by a mean of 23 % over 3-months from an initial value of 167.2 mg/dl . Number of patients reaching the desired blood glucose goals increased from 16.3 % to 39.5 % . Systolic and diastolic blood pressures also significantly fell over 3 months ( mean reductions were 10.9 mmHg for the systolic and 9.3 mmHg for the diastolic blood pressure ) . Number of patients reaching the desired blood pressure goal increased from 30.2 % to 51.2 % . Conclusion Our short-course pharmaceutical care program yielded measurable improvements in clinical indicators of diabetes and comorbidity management . The results suggest that the pharmacist is a beneficial key component of integrated care for patients with type 2 diabetes . We think that the positive results observed in this first reported pharmaceutical care program on diabetes in Turkey can be motivating and encouraging for all community pharmacists BACKGROUND type 2 diabetes mellitus continues to increase in prevalence worldwide . Many factors have been cited as contributing to compliance , such as family and social support , education , number of tablets per dose , frequency of administration and health care provider communication . Toward these goals , the present study was developed to measure the effect offactors on glycemic control such as diabetes education by pharmacists , a diabetes disease booklet and special medication containers . MATERIAL AND METHOD A total of 360 volunteers with type 2 DM patients were recruited , participants were simple r and omized to control 180 and intervention 180 patients . Which intervention categorized to 4 groups ; all intervention groups received diabetes drug counseling by a pharmacist , one group received plus a diabetes booklet , one received plus special medical containers and the last group received all of them . The interventions were done at the 1st time of visit . Both the control and intervention groups were monitored for fasting plasma glucose and HbA1c at 0 , 3 , 6 months and glycemic level in both groups was compared . RESULTS After 3 months , mean fasting plasma glucose and HbA1c decreased wiih the intervention group vs. control group ( 152.36 + /- 39.73 to 131.52 + /- 35.22 mg% ) and ( 150.16 + /- 41.78 to 153.98 + /- 47.95 mg% ) respectively ; ( p < 0.001 ) . HbA1c level 8.16 + /- 1.44 to 7.72 + /- 1.26 vs 8.01 + /- 1.51 to 8.38 + /- 1.46 respectively ; ( p < 0.001 ) . After 6 months , mean fasting plasma glucose and HbA1c decreased with the intervention group vs. control group ( 152.36 + /- 39.73 to 145.20 + /- 46.07 mg% ) and ( 150.16 + /- 41.78 to 159.16 + /- 54.90 mg% ) respectively ; ( p < 0.013 ) . HbA1c level 8.16 + /- 1.44 to 7.91 + /- 1.27 vs. 8.01 + /- 1.51 to 8.80 + /- 1.36 respectively ; ( p < 0.001 ) . The most favorable glycemic outcome was the group that received all of the interventions ; mean FPG was reduced from 147.46 + /- 36.07 to 125.38 + /- 31.12 mg% ( p < 0.000 ) in 1nd visit ( 3 months later ) and still reducing effect on the 2nd visit ( 6 month later ) mean FPG from 147.46 + /- 36.07 to 130.21 + /- 33.96 mg% ( p < 0.016 ) also the same way in HbA 1c level . The group that received only drug counseling by pharmacist had no significant reduction in FPG and HbA1c . ( p > 0.05 ) . CONCLUSION Drug counseling by a pharmacist has little beneficial effect on diabetes management outcome compared to the diabetes booklet and special drug container . To improve glycemic control of type 2 DM is to integrate self-management in daily life , wide a variety of education , drug taken behavior and health care provider available communication produce improvement in patient management and is somewhat better when used in combination Background Childhood asthma is common in Cape Town , a province of South Africa , but is underdiagnosed by general practitioners . Medications are often prescribed inappropriately , and care is episodic . The objective of this study is to assess the impact of educational outreach to general practitioners on asthma symptoms of children in their practice . Methods This is a cluster r and omised trial with general practice s as the unit of intervention , r and omisation , and analysis . The setting is Mitchells Plain ( population 300,000 ) , a dormitory town near Cape Town . Solo general practitioners , without nurse support , operate from storefront practice s. Caregiver-reported symptom data were collected for 318 eligible children ( 2 to 17 years ) with moderate to severe asthma , who were attending general practitioners in Mitchells Plain . One year post-intervention follow-up data were collected for 271 ( 85 % ) of these children in all 43 practice s. Practice s r and omised to intervention ( 21 ) received two 30-minute educational outreach visits by a trained pharmacist who left material s describing key interventions to improve asthma care . Intervention and control practice s received the national childhood asthma guideline . Asthma severity was measured in a parent-completed survey administered through schools using a symptom frequency and severity scale . We compared intervention and control group children on the change in score from pre-to one-year post-intervention . Results Symptom scores declined an additional 0.84 points in the intervention vs. control group ( on a nine-point scale . p = 0.03 ) . For every 12 children with asthma exposed to a doctor allocated to the intervention , one extra child will have substantially reduced symptoms . Conclusion Educational outreach was accepted by general practitioners and was effective . It could be applied to other health care quality problems in this setting Objective The study aim ed at evaluating the effect of pharmaceutical care programme on blood pressure and quality of life of patients who visit a Nigerian community pharmacy . Method A non-r and omised , single-site , crossover design was used . Patients served as their own control . They underwent 5 months of usual care and another 5 months of pharmaceutical care . Main outcome measure Blood pressure and quality of life measured before implementation of pharmaceutical care and at the end served as main outcome measures . Other end-points assessed at baseline and at the end of investigation included smoking cessation , adherence to therapy , exercise , salt restriction , alcohol moderation and self blood pressure measurement . Results Twenty four ( 24 ) patients out of the 40 recruited completed the study . Mean reductions were significant after pharmaceutical care intervention for systolic BP ( 14.3 ± 14.4 mmHg ) and diastolic BP ( 10.8 ± 10.7 mmHg ) . There was a significant mean increase in number of patients that adhered to salt restriction ( −36 % ) , aerobic exercise ( −46 % ) , self BP measurement ( −46 % ) , alcohol moderation ( −33 % ) and drug adherence ( −16.7 % ) . There was a positive increase of −11.4 and −3.2 for physical health and social health domain of quality of life evaluation respectively . Conclusion Pharmaceutical care programme could produce a beneficial effect on hypertensive patients BACKGROUND The practice of pharmaceutical care in primary care setting s in Thail and is currently not generally accepted . OBJECTIVE To evaluate the effect of pharmacist involvement in treatment with hypertensive patients in primary care setting s. METHODS The treatment objective was to stabilize the blood pressure ( BP ) of hypertensive patients in accordance with the Joint National Committee on Prevention , Detection , Evaluation and Treatment of High Blood Pressure guidelines . Patients were r and omly assigned to a pharmacist-involved group ( treatment ) or a group with no pharmacist involvement ( control ) . Pre- and post-test BPs , tablet counts , lifestyle modifications , and pharmacists ’ recommendations were recorded . The 6-month study was carried out in Mahasarakham University pharmacy and 2 primary care units . Patients were monitored monthly by review ing their medications and supported by providing pharmaceutical care and counseling . RESULTS From a total of 235 patients , the treatment group ( n = 118 ) had a significant reduction in both systolic ( S ) and diastolic ( D ) BP compared with the 117 patients of the control group ( p = 0.037 , 0.027 , respectively ) . The 158 patients ( 76 treatment , 82 control ) with BPs 140/90 mm Hg at the beginning of the study showed significant BP reductions ( p = 0.002 SBP , 0.008 DBP ) . The proportion of 158 patients whose BP became stabilized was higher in the treatment group ( p = 0.017 ) . The treatment group showed significantly better adherence ( p = 0.014 ) and exercise control ( p = 0.012 ) at the end of the study . Physicians accepted 42.72 % of medication modifications and 5.34 % of the suggestions for additional investigations . CONCLUSIONS Hypertensive patients who received pharmacist input achieved a significantly greater benefit in BP reduction , BP control , and improvement in adherence rate and lifestyle modification Background : The number of inappropriate prescriptions for sexually transmitted infections ( STIs ) in Sudan is suspected to be high . Simple multifaceted interventions directed at prescribers may improve prescribing patterns in the Sudan . Objective : To evaluate the effect of multifaceted interventions on prescribing for STIs in the White Nile State , Sudan . Methods : The study involved 20 health centres r and omly assigned to four different multifaceted interventions to improve prescribing . Results : Prescriber targeted interventions involving audit and feedback together with academic detailing and practice guidelines reduced the number of inappropriate prescriptions by 50 % ( p<0.001 ) . Audit and feedback together with seminars and practice guidelines reduced inappropriate prescriptions by 43 % ( p<0.001 ) . Audit and feedback alone reduced inappropriate prescriptions by 16 % ( p = 0.127 ) . Conclusion : Prescribing for STIs in the White Nile State of Sudan needs improving . Multifaceted interventions appear effective in improving prescribing AIM : To evaluate the impact of pharmaceutical care on the clinical outcomes of patients enrolled in a pharmacist-coordinated diabetes management program in a rural health setup . SETTING S AND DESIGN : Patients were registered into ‘ control ’ and ‘ intervention ’ groups by r and omization at three primary health centers . The study was an open-label parallel study . MATERIAL S AND METHODS : Medical records were prospect ively review ed . Capillary blood glucose level , blood pressure and demographic data were collected at baseline and at the follow-up visits . Pharmacists gave counseling to the intervention group during every visit and their health-related quality of life ( HRQoL ) was assessed with the Ferrans and Powers question naire . STATISTICAL ANALYSIS : Single factor ANOVA and the t-test were used to compare the results using SPSS version 0.9 software and MS Excel worksheets . RESULTS : The intervention group ( n = 104 ) showed well-controlled BMI , whereas the control group ( n = 50 ) showed significant increase in the BMI . Mean blood glucose level in the intervention group reduced to 25 units from baseline ( P = 0.0001 ) but was significantly increased in the control group ( P = 0.0001 ) . ANOVA showed that from the second follow-up onward there was significant decrease in blood glucose levels . Overall , the HRQoL scores increased by 45 % in the intervention group and decreased by 2 % in the control group . CONCLUSIONS : The pharmaceutical care program was effective in improving the clinical outcome and HRQoL of diabetes patients in rural India . Such ‘ pharmaceutical care ’ models should be fine-tuned and implemented widely OBJECTIVE The aim of this study was to determine whether the provision of further practice -based support by pharmacists will bring about improved outcomes for blood pressure ( BP ) control in middle-aged and elderly Nigerian hypertensive patients managed with combination diuretics ( amiloride hydrochloride 5 mg+hydrochlorothiazide 50 mg ) and /or methyl dopa at the primary care level . DESIGN AND SETTING This was a 1-year prospect i ve , r and omized cohort study of the out patients of a state comprehensive health centre in South-western Nigeria . Free primary health services including free drugs were provided for all patients . PATIENTS AND METHOD The study population comprised 51 Nigerian patients with uncomplicated hypertension aged 45 years or more , with a 0.2 - 3.0-year history of hypertension , registered at the Comprehensive Health Centre , Ife between October 2002 and March 2003 . They were invited into the pharmacist-managed hypertension clinic and followed for the study period . Participating pharmacists counselled for current medication , personalized goals of lifestyle modification stressing weight loss and /or increased activity , increased patient awareness by providing relevant education about hypertension and associated/related diseases , adjusted drug therapy to optimize effectiveness and minimize adverse events , utilized treatment schedules that enhanced patients ' adherence to therapy , and monitored treatment outcomes between enrollment and return visits . Patient satisfaction and the number of treatment failures within 6 months post enrollment were compared with retrospective data from our earlier study involving physician-managed patients under a similar setting . RESULTS Uncontrolled BP reduced from 92 to 36.2 % by 10.15+/-5.02 days after enrollment . Treatment failures were observed at 5.9 % of the total return visits ( n=184 ) within 6 months . CONCLUSION Pharmacist-managed hypertension clinics can improve BP control , reduce treatment failure and increase patient satisfaction The intervention level of epidemiology is useful for study ing effects in health systems research . Due to practical and ethical reasons , it is often difficult to apply experimental methods such as classical r and omized clinical trials in the field . However with alternative approaches such as ' r and omization by group ' some of these problems can be overcome . Drug information has since long been considered as an instrument to influence physicians , however evaluation of its effects is a new field of research . In the present study the impact of drug information on prescribing behaviour was evaluated in an outpatient setting in Sri Lanka . The study included 15 state health institutions ( 45 prescribers ) with a common drug formulary . Groups of prescribers were r and omized into two interventions ; newsletters and newsletters reinforced by a group seminar , and one control group . The target topic was ' rational prescribing of antibiotics ' . Some 18,766 r and omly selected outpatient drug prescriptions were studied . Antibiotics ( and sulphonamides ) were prescribed to 33.2 % of the patients . An overall trend towards a decrease in proportion of patients prescribed antibiotics in the two intervention groups was seen , although the difference was not significant ( p greater than 0.05 ) compared to the control group . This is similar to the effect of written information on prescribing in other studies . A mean difference of -7.4 % in written , -7.3 % in written + seminar and -0.4 % in the control group was shown . The general antibiotic prescribing pattern did not change in any of the three groups . Penicillin was the most commonly prescribed antibiotic and tetracycline was only rarely prescribed to children . This experiment indicates the feasibility of drug information intervention studies in developing countries . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND : This study was conducted to evaluate the effect of a clinical pharmacist-led patient education program for type 2 diabetic patients at Isfahan Endocrine & Metabolism Research Center ( IEMRC ) from April 2008 to January 2009 . METHODS : In a r and omized controlled clinical trial , a total of 172 patients with uncontrolled type 2 diabetes were selected and r and omly allocated into control and intervention groups . After taking informed written consent , the intervention group received an educational program about oral anti-hyperglycemic medications , adherence , diabetes dairy log and pill box usage . Patient 's glycemic control in the intervention group was followed for three months through either telephone or face to face interviews with the pharmacist . Fasting blood glucose and HbA1c were measured at the start and end of the pharmacistled drug education program for both intervention and control groups . RESULTS : After a three months follow-up , mean fasting blood glucose and HbA1c of the patients in the intervention group decreased significantly compared to control group ( p < 0.001 ) . CONCLUSIONS : This study demonstrates an improvement in diabetes management of type 2 diabetics by involving a pharmacist in the multidisciplinary teams in the outpatient clinics . The results suggest the benefits of adding adherence education to the diabetic education programs Objectives To implement and assess hospital-based pharmaceutical care services for patients with asthma . Methods A prospect i ve , r and omized , controlled study was conducted in Shaab teaching hospital , Khartoum , Sudan . Patients were allocated r and omly either in the intervention group ( 60 ) or control group ( 40 ) patients . The drug therapy of asthma for the patients in the intervention group was review ed by a trained pharmacist , and interventions were suggested to the attending physicians for the identified problems . Intervention patients received comprehensive medication counselling and asthma education every 2 weeks , while the control group received the routine medical consultation and dispensing services . The outcome measures were recorded using structured forms at baseline and monitored during a follow-up of every two weeks for 6 months in both groups . Data were analyzed using SPSS version 13 , level of significance was p<0.05 . Results At the end of the study period the mean reduction in frequency of acute attacks ( 1.91 ; SD=0.18 vs. 1.0 ; SD=0.14 ; p=0.03 ) , nocturnal asthma symptoms ( 3.5 ; SD=0.3 vs. 1.1 ; SD=0.2 ; p=0.02 ) and frequency of using inhaled β2 agonists per week ( 19.9 ; SD= 2.1 vs. 3.3 ; SD=0.3 ; p=0.01 ) were significantly greater in the intervention group compared to control . A significant mean reduction ( p=0.002 ) in the days of sickness/week was in the intervention group , while in control group there was an increase in mean days of sickness/week . The intervention group showed a significant greater improvement in the score for assessing the inhalation technique ( p<0.001 ) , patient ’s knowledge about asthma ( p<0.001 ) , and its drug-therapy ( p=0.01 ) compared with control . Conclusion The present findings suggest that pharmacist ’s intervention can have positive impact on asthma-related outcomes in patients There are different kinds of arthritis , widely spread among the population , that make them a clinical problem with social , psychological and economic burden . Different education programs have been developed in order to improve patients ’ disease management , medication compliance and from there patients ’ quality of life . Objective : To develop and implement a community pharmacy-based educational program for patients with arthritis . Improvements in pain , medication compliance , decrease in general practitioner ’s visits and hospitalizations are expected . Methods : Prospect i ve , r and omized , controlled trial . The sample consisted of 43 individuals , with different stages of arthritis ( aged 15 - 71 ) , attending pharmacies – intervention group ; and 43 individuals – control group . A 4-month education was conducted on the following topics : what causes arthritis and what are the factors that can intensify it ; pain management and physical activities ; self-management and prevention ; pharmacotherapy and possible adverse drug reactions . Patient ’s health-related quality of life was assessed in the beginning and at the end of the survey . Results : Parameters assessed during the four stages of the program were : frequency of severe pain , frequency of general practitioner ’s visits , frequency of urgent medical aid calls , compliance with therapy , satisfaction with pharmacy services . Improvement in patients ’ health-related quality of life was observed and also : decrease in the severity of patients ’ pain , decrease in the physician ’s visits , and increase in satisfaction overall care . Conclusions : Positive results from the educational approach in pharmacy conditions were demonstrated . These consequences have a potential to increase arthritis patient ’s quality of life OBJECTIVES To study patterns of outpatient antibiotic use in the Great Tehran , in order to develop interventional strategies in rationalizing drug and especially antibiotic use . MATERIAL S AND METHODS Ten-percent r and om sample of all prescription belonging to practitioners in south of Tehran and kept in a data bank was sample d. Drug use indicators were determined in order to develop intervention program to promote rational drug use among practitioners in Tehran . Based on the values of drug use indicators , an interventional program , a program of continuing medical education ( CME ) targeting rational use of drugs , was design ed . Eighty general practitioners ( GPs ) who contributed to the data bank were selected and allocated to two groups , intervention group and control group . Each group contained 40 GPs . Drug use indicators were measured in each group three times ; before and in two intervals after the intervention . The indicators were compared before and after as well as between groups . RESULTS The drug use indicators determined through the data bank showed that 19 % of all prescribed drugs in data bank were antibiotics , which ranked second only after ' analgesics and CNS drugs ' with 24 % . The drug use indicators were improved in the intervention group ( the average number of drugs per encounter lowered from 4.3 + /- 0.5 pre-intervention to 3.6 + /- 0.1 six months thereafter , p value = 0.001 ) . The percentage of encounters with an antibiotic prescribed were lowered in intervention group compared with control group but the difference was not statistically significant . The intervention made a change to all other measured indicators but not all of them were statistically significant . CONCLUSIONS Irrational use of antibiotics can improve by appropriate educational intervention , using CME programs Asthma is a clinical problem with social , psychological , and economic burdens . To improve patient disease management and quality of life ( QOL ) , different education programs have been developed . The purpose of this study is to adapt and implement a community-based educational program for patients with asthma . A prospect i ve , r and omized , controlled trial was performed . Fifty individuals with mild asthma ( aged 18 - 40 years ) that have been attending pharmacies were included in the sample . The duration of the disease was 9 + /- 4.21 years . A 4-month study was conducted on essence of asthma and factors that can intensify it ; nourishing facts , allergens , and physical activities ; self-management and use of tobacco ; and pharmacotherapy , inhalation technique , and possible adverse drug reactions . Patient 's health-related QOL was assessed in the beginning and at the end of the survey . Parameters assessed during the four stages of the program were patients ' peak expiratory flow ( PEF ) ; inhaler technique ; severe asthma symptoms , including breathlessness , hospitalization rates , frequency of urgent medical aid calls , and frequency of general practitioner visits ; compliance with therapy ; and satisfaction with pharmacy services . Health-related QOL of the intervention patients was improved at 4 months and there was improvement in the PEF rate , decrease in patients ' breathlessness and wheezing rate , decrease in the reported hospitalizations rate because of the disease , decrease in the physician 's visits , and increase in satisfaction with pharmacist-provided information . The positive results from the educational approach show a potential to decrease asthma disease complications and show a positive impact on patients ' inhaler technique , patients ' opinions about the pharmacy services , and information obtained Patient counseling has a significant effect on compliance with prescription regimens , prevent drug interactions and medication errors . This was a self-controlled experimental study to evaluate the effect of patient counseling on blood pressure control in out- patients with hypertension at Chulalongkorn Hospital . Systolic and diastolic pressure of r and omly selected patients were recorded for at least three months before receiving patient counseling . After three months , those patients received counseling on drug , diseases and life-style modification from a pharmacist after a hospital visit and blood pressure was monitored every month for three consecutive months or after each visit . The result showed that 68 patients out of 78 patients could not maintain their blood pressure before receiving counseling . However , after patient counseling , 54 patients had mean arterial pressure within the range specified by the Joint National Committee ( JNC VI ) after the second doctor visit . Patient counseling was highly significant in blood pressure control using the chi-square test ( chi2 = 51.29 ) Objective A major problem with inappropriate use of antibiotics is the emergence of resistance . Thus , cost-effective interventional strategies are required to improve their use . This study aim ed to evaluate the effect of multifaceted interventions on prescribing practice s of antibiotics in health centers of Khartoum State , Sudan . Methods Twenty health centers were r and omly assigned to receive : ( 1 ) no intervention ; ( 2 ) audit and feedback ; ( 3 ) audit and feedback + seminar ; or ( 4 ) audit and feedback + academic detailing . A total of 1,800 patient encounters , 30 from each health center , were r and omly collected . The total number of encounters with antibiotics prescribed were determined in each health center and they were evaluated with regard to antibiotic choice , dose and duration of therapy before the study and at 1 and 3 months post-intervention . Results In comparison to the control group , the prescriber targeted interventions involving audit and feedback , together with academic detailing ( 4 ) , reduced the mean number of encounters with an antibiotic prescribed by 6.3 and 7.7 ( p<0.001 ) at 1 and 3 months post-intervention , respectively . In addition , the mean number of encounters with an inappropriate antibiotic with respect to diagnosis , doses and / or duration of therapy was reduced by 5.3 and 5.9 ( p<0.001 ) at 1 and 3 months post-intervention , respectively . For audit and feedback together with seminars ( 3 ) and for audit and feedback alone ( 2 ) , the corresponding reductions were 5.3 , 7.1 , 4.4 and 5.1 ( p<0.001 ) and 1.4 , 2.8 , 1.8 and 1.9 ( p>0.05 ) , respectively . Conclusion Inappropriate prescribing patterns of antibiotics in health centers of Khartoum State , Sudan , are alarmingly high . Multifaceted interventions involving audit and feedback combined with either academic detailing or seminars appear more effective in changing prescribing practice s of antibiotics than audit and feedback alone PURPOSE Verification of whether pharmacotherapeutic follow-up improves arterial blood pressure ( BP ) was conducted , and whether this improvement alters the quality of life of patients with resistant hypertension in a university teaching hospital in Brazil was determined . METHODS A prospect i ve survey of 44 patients was carried out over a period of 20 months . Each patient was followed up for 12 months . Pharmaceutical care was assessed using the following methods : measurement of the office BP and ambulatory BP monitoring , adherence to therapy , drug-related problems , and the use of health care facilities ( urgent care visits and hospital admissions ) . The health-related quality of life ( HRQOL ) of patients was also assessed using the 36-Item Short Form Health Survey ( SF-36 ) question naire and a physical symptoms profile . RESULTS The majority ( 95.5 % ) of patients adhered to the treatment throughout the study , and there was a significant reduction in BP ( p < 0.05 ) . Nearly all of the domains of HRQOL assessed by SF-36 remained unchanged during the follow-up except for a significant improvement in social functioning ( p = 0.041 ) . There was a significant reduction in moderate and severe physical symptoms ( p = 0.005 ) . There were also significant reductions in the number of urgent care visits ( p = 0.0001 ) and hospital admissions ( p = 0.006 ) . CONCLUSION The pharmaceutical care provided by a pharmacist in an ambulatory care clinic in Brazil improved BP , adherence to antihypertensive medications , and the social functioning of patients with resistant hypertension BACKGROUND : Inappropriate use of medications is a significant problem in health care today . A possible solution to this problem may be achieved through better control of patients ' drug therapy . OBJECTIVE : To design a pharmaceutical care program for dyslipidemic patients within a community pharmacy setting that provides education in the areas of medication compliance and lifestyle modifications , while emphasizing the importance of achieving cholesterol goals to ensure improvement in quality of life . METHODS : Patients at an outpatient pharmacy volunteered to be surveyed for 16 weeks . Although both the intervention and control groups were surveyed , the r and omly selected intervention group was interviewed more frequently and more comprehensively . Cholesterol , triglycerides , glucose , weight , risk factors , drug-related problems ( DRPs ) , and quality of life were measured via a survey at the onset of the study and continually measured until the study 's conclusion . RESULTS : In the intervention group , 26 DRPs were detected , of which 24 were resolved ; in the control group , 26 DRPs were detected , of which 5 were resolved . When comparing initial and final blood cholesterol levels in the intervention group , the mean decrease was 27.0 ± 41.1 mg/dL ( p = 0.0266 ) ; in the control group , the average blood cholesterol level decreased by a mean of 1.4 ± 37.2 mg/dL ( p = 0.6624 ) . In the intervention group , the triglyceride level decreased an average of 50.5 ± 80.3 mg/dL ( p = 0.0169 ) , while the control group experienced a mean triglyceride level increase of 29.6 ± 118.5 mg/dL ( p = 0.1435 ) . As a result of the intervention , the quality of life in the intervention group was improved . CONCLUSIONS : Short-term pharmaceutical care plans developed in a retail pharmacy within the proper setting may contribute to improved blood lipid values , cardiovascular disease risk factors , and patients ' quality of life Objective To evaluate the effects of pharmacotherapy follow-up ( PF ) on metabolic control and clinical outcomes in type 2 diabetic patients . Setting Six community pharmacies ( 4 intervention and 2 control ) in the Curitiba metropolitan region ( Brazil ) . Main outcome measure Glycosylated Haemoglobin A1 ( HbA1 ) and fasting capillary glycaemia . Methods We conducted a 12-month controlled trial involving a total of 161 patients in six community pharmacies between July 2004 and March 2006 . Pharmacotherapy follow-up was applied only to patients in the intervention group . Results Of the 161 patients enrolled , 96 completed the study ( 50 intervention and 46 control ) . The administration of 574 consultations with the intervention group patients led to 119 negative clinical outcomes ( 2.3/patient [ SD = 1.6 ] ) . The majority of detected problems were related to the ineffectiveness of pharmacotherapy ( 68.1 % ) . Relative to the control group , the intervention group exhibited greater glycosylated haemoglobin ( HbA1 ) reduction ( −2.2 % [ 95%CI −2.8%:−1.6 % ] vs. −0.3 [ 95 % CI −0.8:0.2 ] ; P < 0.001 ) and greater fasting capillary glycaemia reduction ( −20.1 mg/dl [ 95 % CI −31.9 mg/dl:−8.3 mg/dl ] vs. 4.3 mg/dl [ 95 % CI −13.4 mg/dl:22.2 mg/dl ] ; P = 0.022 ) . These differences persisted after adjustment for baseline values . There were no significant differences in any other clinical measures between the groups . There were also no significant changes in the number of medications and treatment regimens between groups , with the exception of the percentage of patients undergoing lipid lowering treatment , which increased in the intervention group from 16 % to 24 % ( P = 0.018 ) . The initial medication regimen complexity index ( MRCI ) in the intervention group was 15.5 ( SD = 7.8 , range 4–40.5 ) , and it decreased by 1.2 units ( SD = 5.9 ) after 12 months ( P = 0.149 ) . Conclusions PF of type 2 diabetic patients in community pharmacies can improve the glycaemia control of patients through optimisation of medication profiles without significant changes in either the number of drugs used or the regimen complexity The objective was to determine the influence of medicine labels incorporating pictograms on the underst and ing of instructions and on adherence . Eighty-seven Xhosa participants attending an outpatient clinic who had been prescribed a short course of antibiotics were r and omly allocated to either a control group ( 41 participants given text-only labels ) , or an experimental group ( 46 participants given text + pictogram labels ) . All participants had a maximum of 10 years of formal schooling . Follow-up home visits were conducted after 3 - 5 days to assess underst and ing of instructions and to evaluate adherence . A high adherence of greater than 90 % was found for 54 % of the experimental group , compared with only 2 % of the control group . Average percentages for underst and ing in the control and experimental groups were 70 and 95 % , respectively , and average adherence was 72 and 90 % , respectively . The presence of pictograms was found to contribute positively to both underst and ing of instructions and adherence In an attempt to evaluate the efficacy of different methods of interventions to improve the appropriate use of drugs for acute diarrhoea , a controlled study has been carried out in 6 districts in Yogyakarta and Central Java provinces , Indonesia . This study was design ed to investigate the impacts of two different methods of educational intervention , i.e. a small group face-to-face intervention and a formal seminar for prescribers , on prescribing practice in acute diarrhoea . The districts were r and omly assigned into 3 groups and 15 health centers were selected from each district . Prescribers in Group 1 underwent a small group face-to-face intervention conducted in the respective health center . Those in Group 2 attended a formal seminar conducted at the district level . Prescribers in Group 3 served as the control group . Both interventions were given on a single occasion without follow-up supervision or monitoring . Written information material s on the appropriate management of acute diarrhoea were developed and were provided to all prescribers in the intervention groups . Focus group discussion s ( FGDs ) involving prescribers and consumers in the 6 districts were carried out to identify various underlying motivations of drug use in acute diarrhoea . The findings of the FGDs were used as part of the intervention material s. To evaluate the impacts of these interventions on prescribing practice , a prescribing survey for patients under five years old with acute diarrhoea was carried out in health centers covering 3-month periods before and after the intervention . The results showed that both interventions were equally effective in improving the levels of knowledge of prescribers about the appropriate management of acute diarrhoea . They were also partially effective in improving the appropriate use of drugs , reducing the use of non-rehydration medications . There was a highly significant reduction of antimicrobial usage either after small-group face-to-face intervention ( 77.4 + /- 2.7 % to 60.4 + /- 2.9 % ; P < 0.001 ) or formal seminar ( 82.3 + /- 3.0 % to 72.3 + /- 3.6 % ; P < 0.001 ) , and the former caused significantly ( P < 0.001 ) greater reduction than the latter . There was also a significant ( P < 0.01 ) reduction in the usage of antidiarrhoeals after both interventions , i.e. from 20.3 + /- 3.7 % to 12.5 + /- 3.3 % ( P < 0.01 ) after face-to-face intervention and from 48.5 + /- 4.1 % to 27.0 + /- 4.3 % ( P < 0.01 ) after seminar . However , the formal seminar had a significantly ( P < 0.01 ) greater impact than the small group face-to-face intervention . There was also a trend toward increased oral rehydration solution ( ORS ) usage after both interventions , but this did not achieve the level of statistical significance ( P > 0.05 ) . No changes were observed in the control group . Although the small group face-to-face intervention did not appear to offer greater impacts over large seminars in improving the appropriate use of drugs in acute diarrhoea , since the unit cost of training is far less costly than the seminar , it might be feasibly implemented in the existing supervisory structure of the health system Objective The purpose of this study is to investigate the effectiveness of introducing clinical pharmacy services in achieving goal lipid profile in dyslipidemia patients in North of Jordan . Setting the study was carried out in a primary care facility in North of Jordan . Methods : One hundred fifty two dyslipidemia patients were r and omized into intervention and control groups and followed for 6 months period . Intervention group patients were followed intensively by a clinical pharmacist who worked closely with physicians in controlling lipid profiles according to the third edition of recommendations by The National Cholesterol Education Program Adult Treatment Panel , control group patients were provided with st and ard medical care . Main outcome measure percent of patients at their low density lipoprotein cholesterol target in the intervention group compared to percent of patients at their low density lipoprotein cholesterol target in the control group by the end of the study . Results : One hundred twenty five patients completed the study duration . After 6 months , 94.5 % of intervention group patients and 71.2 % of control group patients reached their goal low density lipoprotein cholesterol levels ( P value < 0.001 , Pearson Chi-Square test ) compared to 24.7 and 28.8 % respectively at baseline . Majority of pharmacist recommendations ( 90.4 % ) were followed by physicians and overall lipid lowering agents use was increased to 91.8 % in intervention group patients and 86.5 % in control group patients compared to 69.9 and 78.8 % respectively at baseline . Conclusion : Implementing clinical pharmacy services in Jordan has improved the lipid profiles of dyslipidemic patients Background : Continuing medical education ( CME ) is compulsory in Iran , and traditionally it is lecture-based , which is mostly not successful . Outcome -based education has been proposed for CME programs . Aim : To evaluate the effectiveness of an outcome -based educational intervention with a new approach based on outcomes and aligned teaching methods , on knowledge and skills of general physicians ( GPs ) working in primary care compared with a concurrent CME program in the field of “ Rational prescribing ” . Method : The method used was cluster r and omized controlled design . All GPs working in six cities in one province in Iran were invited to participate . The cities were matched and r and omly divided into an intervention arm for education on rational prescribing with an outcome -based approach , and a control arm for a traditional program on the same topic . Knowledge and skills were assessed using a pre- and post-test , including case scenarios . Results : In total , 112 GPs participated . There were significant improvements in knowledge and prescribing skills after the training in the intervention arm as well as in comparison with the changes in the control arm . The overall intervention effect was 26 percentage units . Conclusion : The introduction of an outcome -based approach in CME appears to be effective when creating programs to improve GPs ’ knowledge and skills The impact of clinical pharmacists ' consultations on geriatric drug prescribing was studied in a prospect i ve r and omized controlled trial of patients 65 years of age and over discharged on 3 or more medications for chronic conditions from a 450-bed community hospital . The pharmacists provided consultation to experimental patients and their physicians at hospital discharge and at periodic intervals for 3 months postdischarge . Using a st and ardized tool , a physician-pharmacist panel , blinded to study group assignment of patients , evaluated the appropriateness of prescribing for a r and om sample of 236 patients . Eighty-eight percent had at least one or more clinical ly significant drug problems , and 22 % had at least one potentially serious and life-threatening problem . Drug-therapy problems were divided into six categories : 1 ) inappropriate choice of therapy ; 2 ) dosage ; 3 ) schedule ; 4 ) drug-drug interactions ; 5 ) therapeutic duplication ; and 6 ) allergy . Experimental patients were less likely to have one or more prescribing problems in any of the categories ( P = 0.05 ) or in the appropriateness ( P = 0.02 ) or dosage ( P = 0.05 ) categories . A summary score , measuring the appropriateness of the patient 's total drug regimen , indicated that experimental patients ' regimens were more appropriate than those of controls ( P = 0.01 ) . Results of this trial reveal that clinical pharmacists can improve the appropriateness of geriatric drug prescribing in outpatient setting To improve prescribing practice s for rhinopharyngitis , an interactive educational intervention and a managerial intervention were carried out in 18 primary care facilities in metropolitan Mexico City . Four family medicine clinics of the Mexican Social Security Institute ( IMSS ) and 14 health centres of the Ministry of Health ( SSA ) were included . A quasi-experimental design was employed . One hundred and nineteen physicians ( IMSS 68 , SSA 51 ) participated . Sixty-five physicians ( IMSS 32 , SSA 33 ) were in the study group , while 54 were in the control group ( IMSS 36 , SSA 18 ) . The study had four stages : ( I ) baseline , to evaluate the physicians ' prescribing behaviour for rhinopharyngitis ; ( II ) intervention , using an interactive educational workshop and a managerial peer review committee ; ( III ) post-intervention evaluation of short-term impact ; and ( IV ) follow-up evaluation of long-term effect 18 months after the workshop . The control group did not receive any intervention but was evaluated at the same time as the study group . At baseline , most patients in both institutions received antibiotic prescriptions ( IMSS 85.2 % , SSA 68.8 % ) . After the workshop , the percentage of patients receiving antibiotic prescriptions in the IMSS went from 85.2 % to 48.1 % , while in the SSA it went from 68.8 % to 49.1 % . Appropriateness of treatment was analyzed using the physician as the unit of analysis . At baseline , 30 % of IMSS physicians in the study group treated their patients appropriately . After the intervention , this percentage increased to 57.7 % , and at the 18-month follow-up it was 54.2 % . The SSA study group increased the appropriate use of antibiotics from 35.7 % to 46.2 % , with this percentage falling to 40.9 % after the 18-month follow-up period . In the control group there were no significant changes in prescribing patterns with respect to either the prescribing of antibiotics or the appropriateness of treatment . The intervention strategies were successful in both institutions . Forty per cent of physicians improved their prescribing practice s after the workshop , with this change remaining in 27.5 % of them throughout the follow-up period . On the other h and , 42.5 % of the physicians did not change their prescribing practice s after the intervention . The rest ( 17.5 % ) showed appropriate prescribing practice s during all the stages of the study . We conclude that it is possible to improve the physicians ' prescribing practice s through interactive educational strategies and managerial interventions . This type of intervention can be an affordable way to provide continuing medical education to primary care physicians who do not have access to continuing educational activities , and to improve the quality of care they provide This paper presents the results of an intervention study carried out as part of the activities of a District Health Management Team responsible for integrated primary health care delivery in a rural district in Ghana . The aim was to test the impact of a combination of improved information provision to patients and drug labeling on adherence to recommended anti-malarial treatment regimens focusing on oral chloroquine , for the outpatient management of acute uncomplicated malaria . The study had a quasi-experimental pre-test post-test control group design with partly r and om allocation by clinic . The results show that the intervention result ed in an improved flow of information to clients prescribed chloroquine , and better labeling of drugs for the home treatment of acute clinical episodes of malaria in the intervention area . Improvements in adherence occurred in all clinics . However , improvements in adherence were most marked in the clinic that was worst performing at the start of the intervention . Implication s of the results for improving adherence to chloroquine therapy on an outpatient basis are discussed In this study , culturally sensitive visual aids design ed to help convey drug information to nonliterate female adults who had a prescription for a solid oral dosage form of antibiotic medications were developed and evaluated . The research ers conceptualized the educational messages while a local artist produced the visual aids . Seventy-eight female ambulatory patients were evaluated for comprehension and compliance with antibiotic prescription instructions . The study was conducted in three health centers in Cameroon , West Africa and followed a pre-test , post-test , and follow-up format for three groups : two experimental , and one control . All participants were r and omly assigned to either experimental or control groups , 26 patients to each group . Subjects in the experimental groups received visual aids alone or visual aids plus an Advanced Organizer . A comparison of the three groups showed that subjects in the experimental groups scored significantly higher than the control group in both the comprehension and compliance measures BACKGROUND Nigeria has embraced the primary healthcare movement and has committed its re sources to the provision of cost effective community based primary healthcare strategy which recognizes the need for effective partnership between public and private sector . Immunizations are important part of this effort , especially the provision of the vaccines incorporated into the national Exp and ed Programme on Immunization ( EPI ) which has now metamorphosis to National Programme on Immunization ( NPI ) due to decline in immunization coverage . Community pharmacies can be involved in immunization to improve coverage as has been shown in the United States of America ( U.S.A ) that this led to great improvement in immunization coverage . The need to find out if this can also be adopted in Nigeria is the objective of this work . OBJECTIVES This study therefore aim ed to have an insight into current interest of community pharmacists to be involved in routine immunization and assess their physical structures for possible adaptation for use in routine immunization . METHOD Sixty ( 60 ) pre-tested question naires were r and omly administered to community pharmacists . Forty-three ( 43 ) question naires were retrieved for analysis . RESULTS The study revealed that the use of community pharmacies as places where routine immunization services can be provided is feasible as shown by 95.3 % interest expressed by community pharmacists . Most of the required infrastructures to carry out these services are on the ground as shown by availability of adequate space ( 88.4 % ) , st and -by generator ( 83.7 % ) and functional fridge/ freezer ( 95.3 % ) . Community pharmacists ( 88.4 % ) expect to be remunerated for providing this service . CONCLUSION This study has shown the willingness of community pharmacists to participate in immunization efforts and the possibility of using pharmacies in routine immunization OBJECTIVES Prescribing practice s impact greatly on drug use and expenditure . The situation in developing countries is often compounded by a limited health budget . Furthermore , because of role substitution in these countries , prescribers are often not formally trained in rational prescribing . The study described in this paper assesses the effect of a prescribing training intervention for primary health care nurses . DESIGN A generic training-of-trainers course and a 4-day effective prescribing course were presented to 24 provincial trainers . These trainers then conducted effective prescribing workshops for 20 primary health care nurses per workshop . In 1997 , 457 prescribers were trained by this method in South Africa 's Northern Province . The study investigated the impact of the training on prescribing practice s for two target conditions , in a control and a study group of 11 clinics each , 1 month after and 3 months after the intervention . SETTING Primary health care clinics in the Lowveld Region of the Northern Province of South Africa . RESULTS Prescribing practice s for the two conditions examined were significantly improved by the training . Changed behaviour was not only seen in prescribing for upper respiratory tract infections , used as an example condition , but also for diarrhoea and /or vomiting , a common condition in the region , which was not included in the training programme . These results show that prescribers not only retained the knowledge gained , but were also able to apply their new skills to other conditions ( transfer effect ) . The change in the study group was maintained for 3 months after training , while there were no significant improvements in prescribing in the control group . INTERPRETATION The training intervention had a beneficial effect on prescribing practice This study assessed the impact of clinical pharmacists ' consultations on drug regimens , compliance , and health service use of geriatric hospitalized patients ( N = 706 ) discharged on 3 or more medications . Pharmacists consulted with experimental patients at discharge and 3 months thereafter , and with physicians as needed . Controls received usual care . At 6 - 8 weeks after enrollment , experimental patients were more knowledgeable about regimens than controls . At 12 - 14 weeks , they were on fewer medications and less complex regimens , and had better compliance scores . There was no effect on service use or charges , perhaps due to inadequate sample size and lack of targeted drug groups analysis . The authors conclude that clinical pharmacists ' consultations can improve geriatric patients ' drug regimens and compliance . Findings further suggest the need for replication among large cohorts of patients at high risk , due to the use of medications most likely to have a potential for serious outcomes and to be vulnerable to physician prescribing error |
2,270 | 29,786,916 | The results showed that medicinal plants , particularly Sancaijiangtang and Ginkgo biloba could improve behavioral and psychological symptoms , working memory , Mini-Mental State Examination , and activities of daily living as well as neuropsychiatric features . | Vascular dementia ( VaD ) generally refers to memory deficits and cognitive abnormalities that are result ed from vascular disease . | The raised score in the revised Hasegawa dementia scales ( HDS ) demonstrated that the effect of Yi Zhi Capsules ( YZC ) in treating loss of intellectual function after cerebrovascular diseases was significantly better than that of the western drug Piracetam [ symbol : see text ] ( P < 0.01 ) . The morbidity of vascular dementia was much lower in the treatment group than that of the control group ( P < 0.05 ) after a one-year follow-up ; and the blood lipid level and some indexes in rheological examinations were also improved significantly ( P < 0.05 , or < 0.01 ) . The data indicate that YZC is a relatively good preparation for prevention of vascular dementia OBJECTIVES To evaluate whether a traditional Chinese herbal medicine , ba wei di huang wan ( BDW ) , improves cognitive and physical functioning in dementia patients . DESIGN An 8-week r and omized , double-blind , placebo-controlled trial . SETTING Long-term-care facility in Japan . PARTICIPANTS Thirty-three patients with mild to severe dementia ( 7 men and 26 women ; mean age + /- st and ard deviation=84.4 + /- 7.8 ) were recruited and enrolled from May 2002 through September 2002 . INTERVENTION Participants were r and omly assigned to the active drug ( BDW ) group ( n=16 ) or the placebo group ( n=17 ) and treated for 8 weeks . MEASUREMENT Cognitive function and activities of daily living ( ADLs ) ; palsatility index . RESULTS After the trial , cognitive function as assessed using the Mini-Mental State Examination ( MMSE ) significantly improved from 13.5 + /- 8.5 to 16.3 + /- 7.7 ( P<.01 , 95 % confidence interval (CI)=-4.1 to -1.4 ) in the BDW group . The ADL score in the Barthel Index also significantly changed , from 61.8 + /- 34.6 to 78.9 + /- 21.1 ( P<.01 , 95 % CI=-26.2 to -7.9 ) . In contrast , MMSE and Barthel Index scores of the placebo group showed no significant change . Eight weeks after the end of the administration , MMSE and Barthel Index scores of the BDW group declined to the baseline level . The pulsatility index in the internal carotid artery as measured using Doppler sonography significantly decreased in the BDW group ( 2.5 + /- 1.7 to 1.9 + /- 0.5 , P<.05 ) but not in the placebo group . CONCLUSION These results argue the benefits of BDW in the treatment of dementia OBJECTIVE To investigate the therapeutic effects of modified Sanjiasan decoction ( MSD ) on vascular dementia ( VD ) . METHODS Thirty-seven patients in the treated group were given MSD , one dosage each day , and 31 patients in the control group were administered orally Naofukang 0.8 g three times a day . The treatment course for both groups was three months . The indices as Hasegawa dementia scale ( HDS ) , mini mental state examination ( MMSE ) and its subentries , intelligence quotient ( IQ ) and memory quotient ( MQ ) were examined . RESULTS MSD could improve the scores of HDS , MMSE and its subentries ( P<0.05 or P<0.01 ) , ameliorate dementia state and enhance IQ ( P<0.05 ) and MQ ( P<0.01 ) in patients with VD . CONCLUSION MSD has a certain effect on intelligence benefiting and dementia antagonizing OBJECTIVE To observe the effect of Kangxin capsule ( KXC ) on homocysteine ( HCY ) and beta-amyloid protein ( beta-Ap ) in patients with vascular dementia . METHODS Sixty-three patients with vascular dementia were r and omly divided into two groups , the 33 patients in the treated group and the 30 in the control group . Basal treatment were given to both groups , besides , KXC was given to the treated group and Hydergine was given to the control group . The levels of plasma HCY , beta-Ap as well as the changes of mini mental state examination ( MMSE ) , activity of daily living ( ADL ) and TCM Syndrome scoring were observed before and after treatment . RESULTS KXC could significantly decrease the levels of HCY and beta-Ap ( P < 0.01 ) , rise the MMSE scores , reduce ADL scores and ameliorate TCM Syndrome . CONCLUSION KXC can effectively regulate the levels of HCY , beta-Ap in vascular dementia patients OBJECTIVE To observe the validity and safety of Kangxin capsule curing the patients with vascular dementia ( VaD ) . PATIENTS AND METHODS Fifty-six patients with vascular dementia of kidney deficiency and blood stagnation type were selected on the basis of defined diagnostic criteria and were r and omly divided into Kangxin group ( 29 ) and control group ( 27 ) , observing the relevant accumulation scores in dementia scale before and after treatment and changes of endothelin ( ET ) , sex hormone , immunity and routine examinations . RESULTS Kangxin capsule can effectively improve the symptom of patients with VaD of senile kidney deficiency and blood stagnation type , and the average value of curative effect index of 29 patients in the treatment group is 23.01>/=20 % , i.e. effective ; compared with that before treatment , both CD(4 ) and CD(4).CD(8)(-1 ) rises ( P<0.05 ) after the treatment with Kangxin capsule ; for the male VaD patients of the Kangxin group , T level increases ( P<0.05 ) and estrodial ( E(2)).testerone (T)(-1 ) value decreases ( P<0.05 ) after the treatment ; for the female VaD patients of the Kangxin group , E(2 ) , E(2).T(-1 ) value increases a great deal ( P<0.05 ) compared with that before treatment ; ET level of both groups decreased on average ( P<0.01 ) , and did not demonstrate any obvious toxic side effect . CONCLUSIONS Kangxin capsule is a valid and safe preparation of Chinese traditional medicine for curing VaD of senile kidney deficiency and blood stagnation type OBJECTIVE To observe the clinical therapeutic effect of Shuizhitong capsule ( SZT ) in treating senile vascular dementia ( VD ) and on changes of related physio-chemical criteria . METHODS Eighty-five patients with VD were r and omly divided into the treated group ( n = 51 ) and the control group ( n = 34 ) in the ratio of 3:2 , treated with SZT and Piracetam respectively . Before and after treatment , the Zhang 's Dementia Scoring ( HDS ) and Function of Social Activity Question naire ( FAQ ) scoring , cerebral blood flow and hemorrheologic properties were determined . RESULTS SZT could significantly improve the patients ' clinical symptoms , intracranial hemodynamic condition and the hyperviscosity , hypercoagulation and hyperaggregation status , lower the whole blood and plasma specific viscosity , raise the living st and ard of partial patients , with significant difference between before and after treatment ( P < 0.05 ) . CONCLUSION The therapeutic effect of SZT in treating senile VD is definite OBJECTIVE To investigate the effects of scalp-acupuncture on intelligence in patients with vascular dementia ( VaD ) . METHODS A total of 108 VaD patients were r and omly divided into two groups : scalp-acupuncture group and Western medicine group . The scores of Mini-Mental State Examination ( MMSE ) , Blesse Dementia Scale ( BDS ) , Hasegawa Dementia Scale ( HDS ) , Abilities of Daily Life ( ADL ) before and after treatment in the two groups were detected . RESULTS A total of 92 patients completed the treatment . The scores of MMSE , BDS and HDS in the two groups were significantly increased , and the ADL scores significantly declined ( P<0.05 ) . There was no difference in the scores of MMSE , BDS , HDS and ADL between the two groups before and after the treatment . There was no difference in the total effectiveness between the two groups ( P>0.05 ) . CONCLUSION Scalp-acupuncture therapy could improve the clinical intelligence level of VaD patients BACKGROUND Vascular dementia ( VaD ) is the second most prevalent type of dementia among the aged , for whom limited pharmacologic options are available so far . SaiLuoTong capsule is a modern traditional Chinese medicine formula , which has been demonstrated to improve cognition of VaD by the reports of animal experiments and preliminary clinical trial . However , evaluation of this therapy in r and omized multicenter trials is needed . In this article , we present the rationale and design of the SaiLuoTong in Vascular Dementia Study . METHODS This phase 2 clinical trial of SaiLuoTong among patients with mild-to-moderate VaD is a 26-week , multicenter , r and omized , double-blind , placebo-controlled study with a subsequent 26-week , open-label extension . After a 4-week placebo run-in period , participants are central ly r and omized ( 1:1:1 ) to 3 groups : group A receives SaiLuoTong 360 mg per day for 52 weeks ; group B receives SaiLuoTong 240 mg per day for 52 weeks ; group C ( the control group ) are further r and omly assigned to 2 groups in a 1:1 ratio and receives placebo during the double-blind phase , then SaiLuoTong 360 mg per day or SaiLuoTong 240 mg per day during the extension phase . The primary outcome measures include the VaD assessment scale cognitive subscale and the Alzheimer Disease Cooperative Study - clinical global impression of change . Safety measures include body weight , vital signs , electrocardiography , laboratory tests , and records of adverse events . Assuming an attrition rate of 20 % , at least 372 patients are required to obtain a statistical power of 80 % . RESULTS The first patient was enrolled into the study in April 2012 and the completion of the study is expected in September 2014 . CONCLUSIONS The rigorous methodology of the study will hopefully move forward the scientific evaluation of traditional Chinese medicine in treatment of VaD. The results of the present study will provide high- quality evidence on the effect of SaiLuoTong in patients with VaD and has the potential to establish a novel therapeutic approach for this disorder Background and Objective : There are currently no drugs approved to treat vascular dementia (VaD).The objective of this study was to determine if treatment with donepezil , an acetylcholinesterase inhibitor , may provide benefit for VaD patients . Methods : Combined analysis of 2 identical r and omized , double-blind , placebo-controlled , 24-week studies involving 1,219 patients enrolled at 109 investigational sites in the USA , Europe , Canada and Australia . Patients were r and omized to receive donepezil 5 mg/day ( n = 406 ) or 10 mg/day ( after brief titration ; n = 421 ) or placebo ( n = 392 ) . Patients were assessed on cognition [ Alzheimer ’s Disease Assessment Scale – cognitive subscale ( ADAS[-]cog ) , Mini-Mental State Examination ( MMSE ) ] , global function [ Clinician ’s Interview- Based Impression of Change plus ( CIBIC[-]plus ) , Clinical Dementia Rating – Sum of the Boxes ( CDR[-]SB ) ] and function [ Alzheimer ’s Disease Functional Assessment and Change Scale ( ADFACS ) ; instrumental activities of daily living ( ADFACS[-]IADL ) ] . Results : Both donepezil groups showed significant improvements in cognition compared with placebo ( ADAS-cog , MMSE , p < 0.01 ) . Significant global function benefits were seen on the CIBIC-plus in the 5 mg/day group ( placebo vs. 5 mg/day , p < 0.001 ; vs. 10 mg/day , p = 0.006 ) and on the CDR-SB in the 10 mg/day group ( placebo vs. 5 mg/day , p = 0.09 ; vs. 10 mg/day , p < 0.01 ) . Significant functional benefits were also seen ( ADFACS , placebo vs. 5 mg/day , p = 0.08 ; vs. 10 mg/day , p = 0.02 ; ADFACS-IADL , p < 0.05 for both donepezil groups ) . Donepezil was well tolerated , with low withdrawal rates due to adverse events . Conclusions : This combined analysis of the largest trial on VaD to date showed that donepezil-treated patients had significant benefits in cognition , global function and ability to perform IADL . Based on these findings and reported tolerability , donepezil should be considered as an important therapeutic element in the overall management of patients with OBJECTIVE To find a good way to diagnose VD , value the effect of Yishen Yangnao capsule on VD and try to find some rules of changes in Chinese medicine syndromes . METHOD Patients were r and omly divided into treating group and western medicine comparison group . It 's the phase III clinical research of Rishen Yangnao capsule curing VD , judging the validity and security of it , using dukexi slice as comparison drug . Some of the patients did the examination of P300 . RESULT The total validity of Yishen Yangnao capsule is 56.3 % ( contract team is 60.0 % ) . The improve rate of ADL is 0.1069 % ( contract team is 0.1134 % ) . The scores of Chinese medicine syndrome descend . CONCLUSION Yishen Yangnao capsule has the same effect as dukexi slice in curing VD at the side of intelligence situation and life ability BACKGROUND Vascular dementia ( VaD ) is the second common subtype of dementia after Alzheimer 's disease . However , there is still a lack of medication that demonstrates clinical ly relevant symptomatic improvement . Static blood obstructing the brain is the main Chinese medicine syndrome of VaD. OBJECTIVE To evaluate the effects of Chinese medicine for promoting blood circulation and removing blood stasis in patients with mild to moderate VaD. DESIGN , SETTING , PARTICIPANTS AND INTERVENTIONS In this 12-week r and omized , double-blind , parallel-controlled trial , a total of 48 patients with mild to moderate VaD were enrolled between March 2009 and December 2010 . All the patients entered a two-week placebo run-in period followed by a 12-week treatment with Chinese medicine for promoting blood circulation and removing blood stasis ( n=24 ) or placebo ( n=24 ) , respectively . The placebo tablets have the identical taste and appearance as the Chinese medicine tablets . MAIN OUTCOME MEASURES The primary outcome measure was the Alzheimer 's Disease Assessment Scale-cognitive subscale ( ADAS-cog ) ; the secondary outcome measures included the Activities of Daily Living ( ADL ) and the Mini-Mental State Examination ( MMSE ) . RESULTS The Chinese medicine group showed a slight deterioration of 0.25 points and the placebo group showed a deterioration of 2.35 points from baseline by the ADAS-cog , and there was a significant difference between the two groups ( P=0.027 ) . The ADL and the MMSE showed no significant difference from baseline in both groups . Adverse events were rare in both groups . CONCLUSION The Chinese medicine for promoting blood circulation and removing blood stasis may improve cognition and it is safe and well tolerated OBJECTIVE To observe the curative effect of combined Chinese medicine , acupuncture and rehabilitation therapy on vascular dementia ( VD ) , and to compare the Western medicine piracetam . METHODS Total 134 VD patients screened in reference to the st and ard for VD diagnosis in DSM-IV were r and omly divided into a Chinese medicine plus rehabilitation group ( 32 cases ) , a Chinese medicine plus acupuncture group ( 33 cases ) , a Chinese medicine and acupuncture plus rehabilitation group ( 37 cases ) and a Western medicine piracetam group ( 32 cases ) . Mini Mental State Examination ( MMSE ) and Bless Behavior Scale ( BBS ) were used to assess changes in intelligence disorder before treatment and after 12-week treatment . RESULTS BBS score , living ability and daily habit were enhanced after treatment in all groups . Cognitive function and behavioral ability were improved with similar total curative effects in all the 4 groups . Directional ability and short-term memory ability were significantly enhanced after treatment ( P < 0.05 ) in both the Chinese medicine plus rehabilitation group and the Chinese medicine plus acupuncture group groups . Living ability was significantly improved after treatment in the Chinese medicine and acupuncture plus rehabilitation group ( P < 0.01 ) . However , no obvious difference was shown before and after treatment in the piracetam group . CONCLUSION The improvement of living ability in the comprehensive treatment group is better than that in the other groups . Chinese medicine and acupuncture plus rehabilitation treatment can improve intelligence and living ability of senile VD patients Objective : To assess the efficacy and safety of Melissa officinalis extract using a fixed dose ( 60 drops/day ) in patients with mild to moderate Alzheimer ’s disease . Design : A four month , parallel group , placebo controlled trial undertaken in three centres in Tehran , Iran . Methods : Patients with mild to moderate Alzheimer ’s disease aged between 65 and 80 years ( n = 42 ; 18 women , 24 men ) with a score of ≥ 12 on the cognitive subscale of Alzheimer ’s disease assessment scale ( ADAS-cog ) and ≤ 2 on the clinical dementia rating ( CDR ) were r and omised to placebo or fixed dose of Melissa officinalis extract . The main efficacy measures were the change in the ADAS-cog and CDR-SB scores compared with baseline . Side effects were systematic ally recorded . Results : At four months , Melissa officinalis extract produced a significantly better outcome on cognitive function than placebo ( ADAS-cog : df = 1 , F = 6.93 , p = 0.01 ; CDR : df = 1 , F = 16.87 , p < 0.0001 ) . There were no significant differences in the two groups in terms of observed side effects except agitation , which was more common in the placebo group ( p = 0.03 ) . Conclusions : Melissa officinalis extract is of value in the management of mild to moderate Alzheimer ’s disease and has a positive effect on agitation in such patients OBJECTIVE To test the efficacy and safety of a once-daily formulation of EGb 761 in the treatment of patients with dementia with neuropsychiatric features . METHODS Multi-centre trial of 410 out patients with mild to moderate dementia ( Alzheimer 's disease , vascular dementia or mixed form ) scoring between 9 and 23 on the SKT cognitive test battery , at least five on the Neuropsychiatric Inventory ( NPI ) and three or higher in at least one item of the NPI . Patients were r and omly allocated to double-blind treatment with 240 mg of EGb 761 or placebo once daily for 24 weeks . Primary outcomes were the changes from baseline in the SKT total score and the NPI total score . The Alzheimer 's Disease Cooperative Study Clinical Global Impression of Change ( ADCS-CGIC ) , Activities of Daily Living International Scale ( ADL-IS ) , NPI distress score , DEMQOL-Proxy quality -of-life scale and Verbal Fluency Test were secondary outcomes . RESULTS At endpoint , patients treated with EGb 761 ( n = 202 ) improved by -1.4 ( 95 % confidence interval -1.8 ; -1.0 ) points on the SKT and by -3.2 ( -4.0 ; -2.3 ) on the NPI total score , whereas those receiving placebo ( n = 202 ) deteriorated by + 0.3 ( -0.1 ; 0.7 ) on the SKT and did not change on the NPI total score ( -0.9 ; 0.9 ) . Both drug-placebo comparisons were significant at p < 0.001 . EGb 761 was significantly superior to placebo with respect to all secondary outcome measures . Adverse event rates were similar for both treatment groups . CONCLUSIONS EGb 761 , 240 mg once-daily , was found significantly superior to placebo in the treatment of patients with dementia with neuropsychiatric symptoms Two different multicenter studies on the efficacy of Choto-san on patients with vascular dementia , one a well-controlled but non-double blind ( 60 patients ) , the other a double-blind controlled study ( 139 patients ) , were performed . In the well-controlled study , Choto-san was superior in global improvement rating , utility rating and improvement of subjective symptoms , psychiatric symptoms and disturbance in daily living activities . In the double-blind study , with more objective criteria than the well-controlled study , Choto-san was also superior in global improvement rating , utility rating and improvement of subjective symptoms , psychiatric symptoms and disturbance in daily living activities . These results suggest that Choto-san is effective in the treatment of vascular dementia . Uncaria sinensis ( OLIV . ) HAVIL . ( US ) is the main medicinal plant composing Choto-san . Glutamate-induced cell death of cultured cerebellar granule cells was protected by the application of water extract of US in a dose-dependent manner , and concentrations of 10(-5 ) to 10(-4 ) g/ml had a significant effect compared to exposure to glutamate only . Further , the increase of 45Ca2 + influx into cells by glutamate was also blocked by the water extract in a dose-dependent manner . These results suggest that US has a protective effect on glutamate-induced neuronal death in cultured cerebellar granule cells through the inhibition of Ca2 + influx ZusammenfassungIn einer 22-wöchigen , r and omisierten Doppelblindstudie wurden 400 Patienten , die an einer Demenz mit neuropsychiatrischen Symptomen litten , mit Ginkgo-biloba-Extrakt EGb 761 ® ( 240 mg/die ) beh and elt oder erhielten Placebo . Patienten mit wahrscheinlicher Alzheimer-Krankheit , möglicher Alzheimer-Krankheit mit cerebrovaskulärer Erkrankung oder wahrscheinlicher vaskulärer Demenz wurden eingeschlossen , wenn sie Werte zwischen 9 und 23 i m Syndrom-Kurztest ( SKT ) und mindestens 5 Punkte i m Neuropsychiatrischen Inventar ( NPI ) aufwiesen . EGb 761 ® zeigte signifikant bessere Ergebnisse als Placebo in der Zielgröße ( SKT ) und allen Begleitgrößen . Der mittlere zusammengesetzte Skalenwert ( Häufigkeit × Schwere ) des NPI und der mittlere Wert für die Belastung der Betreuungsperson fiel unter EGb 761 ® von 21,3 auf 14,7 bzw . von 13,5 auf 8,7 . Hingegen nahmen die entsprechenden Werte unter Placebo von 21,6 auf 24,1 bzw . von 13,4 auf 13,9 zu ( p < 0.001 ) . Die größten Verum-Placebo-Differenzen zugunsten von EGb 761 ® f and en sich für Apathie/Gleichgültigkeit , Angst , Reizbarkeit/Labilität , Depression/Dysphorie und Schlafstörungen/nächtliches Verhalten . Summary In a r and omised , double-blind , 22-week trial 400 patients with dementia associated with neuropsychiatric features were treated with Ginkgo biloba extract EGb 761 ® ( 240 mg/day ) or placebo . Patients with probable Alzheimer 's disease , possible Alzheimer 's disease with cerebrovascular disease or vascular dementia were eligible if they scored 9 to 23 on the SKT cognitive test battery and at least 5 on the Neuropsychiatric Inventory ( NPI ) . EGb 761 ® was significantly superior to placebo with respect to the primary ( SKT test battery ) and all secondary outcome variables . The mean composite score ( frequency × severity ) and the mean caregiver distress score of the NPI dropped from 21.3 to 14.7 and 13.5 to 8.7 , respectively , in the EGb 761 ® -treated patients , but increased from 21.6 to 24.1 and 13.4 to 13.9 , respectively , under placebo ( p < 0.001 ) . The largest drug-placebo differences in favour of EGb 761 ® were found for apathy/indifference , anxiety , irritability/lability , depression/dysphoria and sleep/nighttime behaviour OBJECTIVE To assess the efficacy of Xianlong Capsule ( XLC ) in treating the senile vascular dementia ( VD ) . METHODS Forty-six cases of VD were r and omly divided into two groups . The XLC group ( 24 patients ) were treated with XLC and the control group ( 22 patients ) were treated with Hydergine . Mini-mental state examination ( MMSE ) , Hamilton depression scale ( HDS ) marks and clinical symptoms were observed in different groups . RESULTS XLC could markedly increase MMSE and HDS marks of VD patients . XLC had the effect of improving balance and gait ability of VD patients . CONCLUSION XLC had certain effect on VD and its effect was better than that of Hydergine OBJECTIVE To evaluate the effectiveness of Chinese medicine granules ( Compound Chinese extract from herbs ) in the treatment on senile vascular dementia . METHOD One hundred and twenty patients meeting criteria for vascular dementia were selected from patients in Dongzhimen Hospital and were r and omly assigned into a treatment group ( n = 70 cases ) , given 1 package of Chinese medicine granules with 1 placebo tablets , and a positive control group ( n = 50 cases ) , given 1 tablets of Duxil with 1 package of placebo . All subjects took this medication 3 times a day for 2 months . Double-blind and double-moulding control were used in this study . At a baseline and end ( two months later ) , all subjects were assessed using a battery consisting of MMSE and Blessed behavior measuring scale . RESULT Both Chinese medicine granules and Duxil could remarkably increase the score of cognition and activity ( P < 0.01 ) . They had Similarly effectiveness and there was no statistical difference between the two groups in effectiveness of increasing memory scores . Chinese medicine granules was better than Duxil in increasing the scores of behavior ( P < 0.05 ) . CONCLUSION Chinese medicine granules has certain effects on vascular dementia . And it has remarkable effectiveness in ameliorating the status of total body . And it can relieve the symptoms in vascular dementia A multi-centre , double-blind , r and omised , placebo-controlled , 24-week trial with 410 out patients was conducted to demonstrate efficacy and safety of a 240 mg once-daily formulation of Ginkgo biloba extract EGb 761 ( ® ) in patients with mild to moderate dementia ( Alzheimer 's disease or vascular dementia ) associated with neuropsychiatric symptoms . Patients scored 9 to 23 on the SKT cognitive battery , at least 6 on the Neuropsychiatric Inventory ( NPI ) , with at least one of four key items rated at least 4 . Primary outcomes were the changes from baseline to week 24 in the SKT and NPI total scores . The ADCS Clinical Global Impression of Change ( ADCS-CGIC ) , Verbal Fluency Test , Activities of Daily Living International Scale ( ADL-IS ) , DEMQOL-Proxy quality -of-life scale and 11-point box scales for tinnitus and dizziness were secondary outcome measures . Patients treated with EGb 761 ( ® ) ( n = 200 ) improved by 2.2 ± 3.5 points ( mean ± sd ) on the SKT total score , whereas those receiving placebo ( n = 202 ) changed only slightly by 0.3 ± 3.7 points . The NPI composite score improved by 4.6 ± 7.1 in the EGb 761( ® )-treated group and by 2.1 ± 6.5 in the placebo group . Both drug-placebo comparisons were significant at p < 0.001 . Patients treated with EGb 761 ( ® ) also showed a more favourable course in most of the secondary efficacy variables . In conclusion , treatment with EGb 761 ( ® ) at a once-daily dose of 240 mg was safe and result ed in a significant and clinical ly relevant improvement in cognition , psychopathology , functional measures and quality of life of patients and caregivers OBJECTIVE To observe the clinical effect of Yuantong Capsule ( YTC ) in treating vascular dementia ( VD ) . METHODS Eighty-three patients of VD were r and omized on ratio of 2:1 into two groups , the 54 patients in the treated group were treated with YTC orally administered , 3 times a day , 1 capsule in each time . The remaining 29 patients in the control group were treated with Hydergine orally , 3 times a day , 2 mg in each time . The therapeutic course for both groups was 2 months . RESULTS The therapeutic effect in the treated group was significantly better than that in the control group , significant difference ( P < 0.05 or P < 0.01 ) was shown in comparison of the two groups in terms of the mini-mental state examination ( MMSE ) and activity of daily living ( ADL ) test , symptoms scoring , total effective rate , and laboratory indexes findings . CONCLUSION The therapeutic effect of YTC in treating VD was obvious OBJECTIVE To observe the effect of Chinese herbal medicine in treating vascular dementia ( VD ) and to explore the method for therapeutic effect evaluation . METHODS Multi-center , double-blinded r and omize-controlled method was adopted to observe the effect of treatment of 242 patients with VD of mild or middle degree , they were 89 cases in the TCM group , 106 cases in the western medicine group and 47 in the placebo group . Minimental state examination ( MMSE ) , Blessed dementia scoring on TCM symptom classified evaluation were used to evaluate the therapeutic effect after 60 days treatment . RESULTS The total effective rate of Jiannao Yizhi Granule was 58.4 % , showing a better effect than that of the placebo group and the western medicine group respectively . The treatment was superior in holistic regulation and systemic functional state improvement , it could not only improve the mild middle key symptoms of VD and the mental disorder induced reduction of functional activities , but also alleviate or eliminate the peripheral symptoms of VD . CONCLUSION The effect of treatment of vascular dementia by Jiannao Yizhi Granule is certain and is worth spreading OBJECTIVE To assess the therapeutic effect of auricular point taping and pressing therapy on vascular dementia ( VD ) . METHODS One hundred and eighty cases of vascular dementia were r and omly divided into an auricular point taping and pressing group and a western medicine group , 90 cases in each group . The auricular point taping and pressing group was treated by auricular point taping and pressing at auricular points Shennen , Nao ( brain ) , Shen ( kidney ) , Zhen ( pulvinal ) , and the western medicine group by oral administration of Nimodipine , thrice each day , 30 mg each time . They were treated for 12 weeks . The scores of mini-mental state examination ( MMSE ) and activities of daily living ( ADL ) , and adverse reaction were observed . RESULTS The scores of MMSE before treatment and 12 weeks after treatment were 18.00 + /- 3.88 and 20.83 + /- 3.74 in the auricular point taping and pressing group , and 17.80 + /- 3.82 and 20.70 + /- 3.53 in the western medicine group , respectively , with significant increases in scores of MMSE after treatment in the two groups ( both P < 0.01 ) and with no significant difference between the two groups ( P > 0.05 ) . The scores of ADL before treatment and 12 weeks after treatment were 44.90 + /- 14.84 and 39.60 + /- 12.45 in the auricular point taping and pressing group , and 45.70 + /- 14.86 and 39.10 + /- 13.44 in the western medicine group , respectively , with significant decreases after treatment in the two groups ( both P < 0.01 ) and with no significant difference between the two groups ( P > 0.05 ) . In the auricular point taping and pressing group , 2 cases withdrew from the test because adhesive plaster allergic reaction induced severe itch of the auricle . In the western medicine group , one case had mild dizziness and another case had diarrhea respectively . CONCLUSION Auricular point taping and pressing and Nimodipine have similar therapeutic effect on vascular dementia , and have no obvious adverse reaction , except adhesive plaster allergic reaction OBJECTIVE To investigate the clinical effect of Tianzhi Granule ( TZK ) on senile vascular dementia ( VaD ) , which is classified as sthenia of liver-yang . METHOD Two hundred VaD patients were treated with TZK ( 0.5 g/bag ) , which was taken one bag each , three times a day . The treatment course was one month and they were treated for rwo courses . RESULT TZK could remarkably increase gnosia and activity , with no striking difference from that of positive control group ( P > 0.05 ) . Simultaneously , TZK could significantly improve the clinical syndrome of traditional Chinese medicine and viability . It could also drastically reduce the whole blood and plasma viscosity and improve erythrodegeneration and abnormality of aggregation index in the abnormal blood viscosity patients . CONCLUSION TMC has certain effects on senile OBJECTIVE To observe clinical curative effect of Shenxiong Bushen Capsule for the treatment of mild vascular dementia ( VaD ) , and probe the partial mechanism . METHODS With a block r and om , double-blinded and controled clinical research method adopted , seventy patients with VaD were r and omly assigned to two groups in a ratio of 5:2 , including 50 cases in the trial group and 20 cases in the control group . The patients in the trial group were given the Shenxiong Bushen Capsule ( 5 tablets , thrice a day ) , while those in the control group were given Piracetam ( 5 tablets , twice a day ) . All patients of the two groups were treated for 2 months , and one third cases were follow-up surveyed for 1 month . The cognitive ability , the activities of daily living , Chinese medicine syndrome of VaD , and the quality of life were measured respectively before and after the treatment . RESULTS According to the Mini-Mental State Examination , the clinical effects of patients showed that there was insignificant difference between the trial group ( total effective rate was 74.46 % and 80.85 % , respectively ) and the control group ( total effective rate was 68.42 % and 78.95 % , respectively ) on the cognitive ability and the activities of daily living ( P > 0.05 ) , while the curative effect of the trial group ( total effective rate was 85.11 % ) was superior to that of the control group ( total effective rate was 63.16 % ) on Chinese medicine syndrome of VaD , and had significant difference between the two groups ( P < 0.05 ) . The results measured by WHOQOL-SF36 indicated that the total scores and the scores of each field in both the trial group and the control group after treatment increased more than those of before treatment ( P < 0.01 , P < 0.05 ) , except physical function ( PF ) field and role physical ( RP ) field of the control group ( P > 0.05 ) . The scores of the trial group about total body , PF field , RP field and vitality ( VT ) field increased more than those of the control group ( P < 0.05 ) ; while no difference was shown between the trial group and control group in the scores of bodily pain field , role emotional field , general health field , social function field and mental health field ( P > 0.05 ) . CONCLUSION Shenxiong Bushen Capsule has a definite curative effect on mild VaD , and it can improve the quality of life of patients . Adopting the SF36 Scale to evalute the quality of life of patients with VaD has significance and avaibility to some extent Objective : To evaluate the efficacy and tolerability of donepezil in patients with vascular dementia ( VaD ) . Methods : Patients ( n = 616 ; mean age , 75.0 years ) with probable or possible VaD , according to National Institute of Neurological Disorders and Stroke – Association Internationale pour la Recherche en l’Enseignement en Neurosciences criteria , were r and omized to receive donepezil 5 mg/day ( n = 208 ) , donepezil 10 mg/day ( after 5 mg/day for the first 28 days ) ( n = 215 ) , or placebo ( n = 193 ) for 24 weeks . Results : Seventy-six percent of the patients enrolled had probable VaD. A total of 75.3 % of the 10 mg donepezil group and 80.8 % of the 5 mg group completed the study compared with 83.4 % of the placebo group . Both donepezil-treated groups showed improvements in cognitive function on the Alzheimer ’s Disease Assessment Scale – cognitive subscale compared with placebo , with a mean endpoint treatment difference , as measured by the change from baseline score , of approximately 2 points ( donepezil 5 mg , −1.65 [ p = 0.003 ] ; 10 mg , −2.09 [ p = 0.0002 ] ) . Greater improvements on the Clinician ’s Interview-Based Impression of Change – plus version were observed with both donepezil groups than with the placebo group ( overall donepezil treatment vs placebo p = 0.008 ) ; 25 % of the placebo group showed improvement compared with 39 % ( p = 0.004 ) of the 5 mg group and 32 % ( p = 0.047 ) of the 10 mg group . Withdrawal rates due to adverse events were low ( placebo , 8.8 % ; donepezil 5 mg , 10.1 % ; 10 mg , 16.3 % ) . Conclusions : Donepezil-treated patients demonstrated significant improvements in cognition and global function compared with placebo-treated patients , and donepezil was well tolerated WHAT IS KNOWN Herbal medicines have been used in the treatment of behavioural and psychological symptoms of dementia but with variable response . Crocus sativus ( saffron ) may inhibit the aggregation and deposition of amyloid β in the human brain and may therefore be useful in Alzheimer 's disease ( AD ) . OBJECTIVE The goal of this study was to assess the efficacy of saffron in the treatment of mild to moderate AD . METHODS Forty-six patients with probable AD were screened for a 16-week , double-blind study of parallel groups of patients with mild to moderate AD . The psychometric measures , which included AD assessment scale-cognitive subscale ( ADAS-cog ) , and clinical dementia rating scale-sums of boxes , were performed to monitor the global cognitive and clinical profiles of the patients . Patients were r and omly assigned to receive capsule saffron 30 mg/day ( 15 mg twice per day ) ( Group A ) or capsule placebo ( two capsules per day ) for a 16-week study . RESULTS After 16 weeks , saffron produced a significantly better outcome on cognitive function than placebo ( ADAS-cog : F=4·12 , d.f.=1 , P=0·04 ; CDR : F=4·12 , d.f.=1 , P=0·04 ) . There were no significant differences in the two groups in terms of observed adverse events . WHAT IS NEW AND CONCLUSION This double-blind , placebo-controlled study suggests that at least in the short-term , saffron is both safe and effective in mild to moderate AD . Larger confirmatory r and omized controlled trials are called for OBJECTIVE To observe the effect of Sancaijiangtang powders on plasma nitric oxide and endothelin-1 levels . We sought to identify the common pathological link and mechanism of action for Traditional Chinese medicine in type 2 diabetes mellitus and vascular dementia , and to explicate the material basis for treating the different diseases with the same method in Traditional Chinese Medicine . METHODS In total , 168 patients with type 2 diabetes mellitus and vascular dementia were enrolled in the study , and r and omly divided into two groups by simple r and omization . Patients in the treatment group received oral Sancaijiangtang powders with pioglitazone hydrochloride three times daily , while patients in the control group received pioglitazone hydrochloride alone . The treatment course was for 12 weeks . Mini-mental state examinations ( Chinese version ) and Montreal Cognitive Assessment s ( Beijing version ) were performed , and fasting plasma glucose , fasting insulin , hemoglobin A1c , homeostasis model assessment of insulin resistance , plasma nitric oxide and endothelin-1 levels were measured before and after the treatment . RESULTS The post-treatment levels for all measurements in both groups were better than pre-treat- ment levels ( P < 0.05 ) . The post-treatment levels for all measurements in the treatment group were better than the levels measured in the control group ( P < 0.05 ) . CONCLUSION Type 2 diabetes mellitus and vascular dementia have common pathological mechanisms for insulin resistance and endothelium dysfunction . Sancaijiangtang powders could improve the release of nitric oxide and inhibit the secretion of endothelin-1 . Therefore , the material basis exists for treating the different diseases with the same method in Traditional Chinese Medicine Previous clinical trials suggest that the traditional Japanese medicine yokukansan has beneficial effects on the behavioral and psychological symptoms of dementia ( BPSD ) . The present study was conducted to eluci date the efficacy of yokukansan on BPSD in patients with vascular dementia . Thirteen Japanese patients ( 9 men and 4 women ) who were diagnosed as having vascular dementia ( VaD ) according to the diagnostic criteria of NINDS-AIREN were subjected to the open-label clinical trial in which yokukansan ( 7.5g/day ) has been given for 4 weeks . Their mean age was 71.2±6.5 years . The BPSD was evaluated using the Neuropsychiatric Inventory ( NPI ) , cognitive function was evaluated by the Mini-Mental State Examination ( MMSE ) , the activities of daily living was evaluated by Barthel index ( BI ) and Disability Assessment for Dementia ( DAD ) , and the extrapyramidal signs were evaluated by United Parkinson 's Disease Rating Scale ( UPDRS ) . The mean NPI was 33.0±17.3 and 23.6±13.9 for the baseline and after treatment , respectively . It was significantly improved after treatment ( p<0.05 ) . In the NPI-subcategories , there was a significant improvement in agitation and disinhibition after the treatment . There was no significant change in MMSE , BI , DAD or UPDRS before and after the treatment . There was no adverse effect during the treatment period . The present results suggest that yokukansan is beneficial for the treatment of BPSD in VaD patients OBJECTIVE Herbal remedies play an important role in treatment of psychiatric disorders . The aim of this study was to assess the efficacy of crocin , the main active constituent of saffron , as an adjunctive treatment in major depressive disorder ( MDD ) . METHOD This study was a r and omized , double-blind , placebo-controlled , pilot clinical trial . It was carried out during 4 weeks in two groups ( placebo and treatment ) on 40 MDD patients between 24 and 50 years old in Ibn-e-Sina psychiatric hospital , Mashhad , Iran , from March 2013 to December 2013 . The crocin group ( n=20 ) was given one selective serotonin reuptake inhibitor ( SSRI ) drug ( fluoxetine 20mg/day or sertraline 50mg/day or citalopram 20mg/day ) plus crocin tablets ( 30mg/day ; 15 mg BID ) and placebo group ( n=20 ) was administered one SSRI ( fluoxetine 20mg/day or sertraline 50mg/day or citalopram 20mg/day ) plus placebo ( two placebo tablets per day ) for 4 weeks . Both groups filled beck depression inventory ( BDI ) , beck anxiety inventory ( BAI ) , general health question naire ( GHQ ) , the mood disorder question naire ( MDQ ) , side effect evaluation question naire , and demographic question naire before and after one month intervention . RESULTS The crocin group showed significantly improved scores on BDI , BAI and GHQ compared to placebo group ( Pvalue<0.0001 ) . The averages of decrease in BDI , BAI and GHQ scores in placebo group were 6.15 , 2.6 and 10.3 respectively , whereas the values in crocin group were 17.6 , 12.7 and 17.2 after 4 weeks trial . LIMITATIONS Poor patient compliance with medications and short trial period , small sample size and self-report assessment s were the major limitations of this study . CONCLUSION These results demonstrated the effect of crocin in depression and could be administered in treatment of MDD patients |
2,271 | 24,990,381 | There is moderate quality evidence that rates of donor deferral due to low haemoglobin are considerably less in those taking iron supplements compared with those without iron supplementation , both at the first donation visit and at subsequent donation .
Iron-supplemented donors also show elevated haemoglobin and iron stores . | BACKGROUND Iron deficiency is a significant cause of deferral in people wishing to donate blood .
If iron removed from the body through blood donation is not replaced , then donors may become iron deficient .
All donors are screened at each visit for low haemoglobin ( Hb ) levels .
However , some deferred blood donors do not return to donate .
Deferred first-time donors are even less likely to return .
Interventions that reduce the risk of provoking iron deficiency and anaemia in blood donors will therefore increase the number of blood donations .
Currently , iron supplementation for blood donors is not a st and ard of care in many blood services .
A systematic review is required to answer specific questions regarding the efficacy and safety of iron supplementation in blood donors .
OBJECTIVES To assess the efficacy and safety of iron supplementation to reduce deferral , iron deficiency and /or anaemia in blood donors . | To determine if high doses of oral iron could shorten the duration of therapy necessary to treat Fe deficiency anemia , high-dose Fe 600 mg three times per day ( given as nontoxic carbonyl Fe ) was compared with st and ard ferrous sulfate 60 mg Fe++ three times per day in a r and omized , double-blind , 3-wk trial involving 36 female blood donors with mild Fe deficiency anemia . In animal studies , both forms of Fe have similar bioavailability when administered in equal amounts . High-dose carbonyl Fe was well tolerated with gastrointestinal side effects similar those observed with st and ard FeSO4 therapy . The 10-fold larger amount of Fe result ed in a mean 1.5-fold increase in estimated Fe absorption . Both regimens corrected anemia but neither replenished storage Fe . These results suggest that the principal advantage to the use of carbonyl Fe would derive from its safety rather than from the large doses that can be given We assessed changes in iron stores and iron absorption after repeat blood donations using a combination of biochemical measures of iron status : ferritin , hemoglobin , and transferrin saturation . Thirty-six volunteers with a mean ( + /- SD ) age of 67.7 + /- 3.7 y donated an average of 15 units of blood over 3.5 y. Initial iron stores were 12.45 + /- 3.09 mg/kg for men and 12.53 + /- 3.24 mg/kg for women . Of the 20 men and 16 women who completed the study , 6 men and 10 women were taking a self-selected supplement providing approximately 20 mg Fe/d . Dietary iron intake was determined to be approximately 20 mg/d for men and approximately 18 mg/d for women . Decreases in iron stores in supplemented men were not significantly different from those in nonsupplemented men : 9.52 + /- 2.57 and 11.31 + /- 2.74 mg/kg , respectively . Nonsupplemented women showed a significantly ( P < 0.05 ) greater decline in iron stores than did supplemented women : 13.09 + /- 2.46 and 10.60 + /- 4.15 mg/kg , respectively . Mean maximal iron absorption was approximately 4.10 mg/d for men and approximately 3.55 mg/d for women regardless of iron intake BACKGROUND Iron depletion or deficiency in blood donors frequently results in deferrals for low hemoglobin ( Hb ) , yet blood centers remain reluctant to dispense iron replacement therapy to donors . STUDY DESIGN AND METHODS During a 39-month period , 1236 blood donors deferred for a Hb level of less than 12.5 g/dL and 400 nondeferred control donors underwent health history screening and laboratory testing ( complete blood counts , iron studies ) . Iron depletion and deficiency were defined as a ferritin level of 9 to 19 and less than 9 µg/L in females and 18 to 29 and less than 18 µg/L in males . Deferred donors and iron-deficient control donors were given a 60-pack of 325-mg ferrous sulfate tablets and instructed to take one tablet daily . Another 60-pack was dispensed at all subsequent visits . RESULTS In the low-Hb group , 30 and 23 % of females and 8 and 53 % of males had iron depletion or deficiency , respectively , compared with 29 and 10 % of females and 18 and 21 % of males in the control group . Iron-depleted or -deficient donors taking iron showed normalization of iron-related laboratory parameters , even as they continued to donate . Compliance with oral iron was 68 % . Adverse gastrointestinal effects occurred in 21 % of donors . The study identified 13 donors with serious medical conditions , including eight with gastrointestinal bleeding . No donors had malignancies or hemochromatosis . CONCLUSION Iron depletion or deficiency was found in 53 % of female and 61 % of male low-Hb donors and in 39 % of female and male control donors . Routine administration of iron replacement therapy is safe and effective and prevents the development of iron depletion and deficiency in blood donors BACKGROUND The consequences of temporary deferral are not well understood . This study sought to investigate blood donor return after deferral expiration . STUDY DESIGN AND METHODS A retrospective cohort analysis of allogeneic whole-blood donation was conducted . All deferred donors and a r and om sample of eligible donors were identified from the year 2000 , with subsequent blood center visits through December 2005 captured . Stratified results are reported as the percentage returning , rates of return , and time to return . Measures of statistical association and Cox regression modeling are reported . RESULTS For first-time ( FT ) donors , 25 percent of temporarily deferred donors returned during the 5-year follow-up period compared to 47 percent of eligible donors ( p < 0.0001 ) ; for repeat donors , 81 and 86 percent of deferred and eligible donors returned , respectively ( p < 0.0001 ) . Depending on the deferral category , 14 to 31 percent of FT and 58 to 90 percent of repeat donors returned . Rates ( per year ) of successful donation during the follow-up period were 0.09 for index-deferred FT donors , 0.28 for eligible FT donors , 1.0 for deferred repeat donors , and 1.45 for eligible repeat donors . Multivariate modeling indicated that in addition to deferral , age , sex , race , and education were associated with return in both FT and repeat donors . CONCLUSION The effects of deferral were more pronounced than expected , affecting both FT and repeat donors . For FT donors , the type and duration of deferral , while important , were not as relevant as hypothesized because so few returned , suggesting the need to develop appropriate interventions to recapture those donors likely to be eligible Absolute iron deficiency is treated by correcting the causative lesion and then , traditionally , administering sufficient amounts of ferrous salt to return the haemoglobin level to normal and replenish body stores . The bioavailability of ferric compounds has been question ed and accordingly their therapeutic role remains controversial . A special problem is posed by regular blood donation , where the frequency of phlebotomy is limited by the haemoglobin level , which , in turn , requires maintenance of an adequate supply of iron from dietary sources . Since this latter situation may not always occur , it would be of practical benefit to have a form of supplementation that is effective and can be taken without side effects . These issues were prospect ively examined in a consecutive series of otherwise healthy blood donors who developed absolute iron deficiency anaemia and were then r and omly allocated to receive 60 mg of this metal as ferrous sulphate twice a day ( Group 1 : n = 51 ) , 100 mg as chewable ferric polymaltose daily ( Group 2 : n = 53 ) , or the latter product twice a day ( Group 3 : n = 55 ) . Serial studies showed that 80 % of patients in Groups 1 and 3 had reached normal haemoglobin levels by 12 weeks , but this figure was only 50 % in Group 2 . Similarly , the proportion of patients improving their percentage saturation of transferrin to within the normal range was significantly better in Groups 1 and 3 than in Group 2 ( P < .01 ) . However , body iron stores , reflected in serum ferritin level , was significantly better in Group 1 ( P < .01 ) ; there was no difference in this respect between Groups 2 and 3 . ( ABSTRACT TRUNCATED AT 250 WORDS Background Iron deficiency without anemia is related to adverse symptoms that can be relieved by supplementation . Since a blood donation can induce such an iron deficiency , we investigated the clinical impact of iron treatment after a blood donation . Methods One week after donation , we r and omly assigned 154 female donors with iron deficiency without anemia , aged below 50 years , to a four-week oral treatment of ferrous sulfate versus a placebo . The main outcome was the change in the level of fatigue before and after the intervention . Aerobic capacity , mood disorder , quality of life , compliance and adverse events were also evaluated . Hemoglobin and ferritin were used as biological markers . Results The effect of the treatment from baseline to four weeks of iron treatment was an increase in hemoglobin and ferritin levels to 5.2 g/L ( P < 0.01 ) and 14.8 ng/mL ( P < 0.01 ) , respectively . No significant clinical effect was observed for fatigue ( -0.15 points , 95 % confidence interval -0.9 points to 0.6 points , P = 0.697 ) or for other outcomes . Compliance and interruption for side effects was similar in both groups . Additionally , blood donation did not induce overt symptoms of fatigue in spite of the significant biological changes it produces . Conclusions These data are valuable as they enable us to conclude that donors with iron deficiency without anemia after a blood donation would not clinical ly benefit from iron supplementation . Trial Registration Clinical Trials.gov : Regular blood donors were enrolled in a double-blind , parallel group study to evaluate the side effects of two iron supplements , one containing both heme iron and non-heme iron ( Hemofer , 2 tablets = 18 mg iron/day ) , the other non-heme iron only ( Erco-Fer ; 1 tablet = 60 mg iron/day ) . No differences were found between the two alternatives in regaining predonation iron status as measured by serum ferritin and hemoglobin levels . Despite this therapeutic equivalence , participants ' symptom diaries showed substantial differences in the side effects for the two treatments . The frequency of constipation ( p < 0.05 ) and the total incidence of all side effects ( p < 0.01 ) were significantly higher for non-heme iron when compared with the heme iron-non-heme iron combination and a placebo . The study demonstrates that a low-dose iron supplement containing both heme iron and non-heme iron ( Hemofer ) has fewer side effects when compared with an equipotent , traditional non-heme iron supplement Seventeen conscripts gave blood every second month , the amount representing an average iron loss of 3.5 mg daily . Seven of them were given 20 mg and ten 100 mg iron as ferrous carbonate once daily throughout the study . Before the first and after the fourth and sixth blood donations they were examined with regard to packed red cell volume , serum iron , total iron-binding capacity and stainable bone marrow iron , and a diagnostic iron absoprtion test was performed . Ten conscripts receiving no iron and giving no blood but comparable to those in the test groups with regard to age , exercise and diet served as controls . The stainable bone marrow iron was found to become stabilized at a level with reduced but still perceptible amounts when 20 mg iron was given , and at a level with somewhat greater amounts when the daily dose was 100 mg . Both levels were lower than before blood donation in most subjects , and the negative iron balance was also reflected in the diagnostic iron absorption test . When a healthy person loses 3.5 mg iron daily , supplementation with a 100 mg tablet per day is therefore insufficient to maintain the iron stores at their previous level . The decrease in storage iron is not progressive , however . When the storage iron is reduced , iron absorption seems to be stimulated sufficiently to establish a balance at a reduced storage iron level Background There is no recommendation to screen ferritin level in blood donors , even though several studies have noted the high prevalence of iron deficiency after blood donation , particularly among menstruating females . Furthermore , some clinical trials have shown that non-anaemic women with unexplained fatigue may benefit from iron supplementation . Our objective is to determine the clinical effect of iron supplementation on fatigue in female blood donors without anaemia , but with a mean serum ferritin ≤ 30 ng/ml . Methods / Design In a double blind r and omised controlled trial , we will measure blood count and ferritin level of women under age 50 yr , who donate blood to the University Hospital of Lausanne Blood Transfusion Department , at the time of the donation and after 1 week . One hundred and forty donors with a ferritin level ≤ 30 ng/ml and haemoglobin level ≥ 120 g/l ( non-anaemic ) a week after the donation will be included in the study and r and omised . A one-month course of oral ferrous sulphate ( 80 mg/day of elemental iron ) will be introduced vs. placebo . Self-reported fatigue will be measured using a visual analogue scale . Secondary outcomes are : score of fatigue ( Fatigue Severity Scale ) , maximal aerobic power ( Chester Step Test ) , quality of life ( SF-12 ) , and mood disorders ( Prime-MD ) . Haemoglobin and ferritin concentration will be monitored before and after the intervention . Discussion Iron deficiency is a potential problem for all blood donors , especially menstruating women . To our knowledge , no other intervention study has yet evaluated the impact of iron supplementation on subjective symptoms after a blood donation . Trial registration BACKGROUND AND OBJECTIVES Iron depletion is common in regular blood donors . The objective of the study was to investigate the frequency and severity of iron depletion in regular blood donors and whether IV iron is more effective than oral to avoid iron depletion and symptoms thereof , especially restless legs syndrome ( RLS ) . METHOD One hundred and twenty blood donors with at least five previous whole blood donations were r and omized to receive either IV iron sucrose ( Venofer ( ® ) , RenaPharma/Vifor , Uppsala , Sweden ) , 200 mg , or to 20 × 100 mg of oral iron sulphate ( Duroferon ( ® ) , GlaxoSmithKline , Stockholm , Sweden ) , after each blood donation during 1 year . Iron status and RLS incidence and severity were investigated . RESULTS Iron status was generally poor among regular blood donors , especially in women , with a high incidence of iron depletion ( > 20 % ) and RLS ( 18 % ) . The IV iron group increased storage iron to a greater extent than the oral iron group after 12 months ( P=0·0043 ) . Female donors were more responsive to IV iron sucrose compared to oral iron sulphate , particularly female donors below 50 years of age . RLS severity scores were significantly lower in the IV iron group . The two treatments were safe . CONCLUSION Iron status is poor in regular blood donors , restless legs syndrome is common , and the routine iron supplementation is insufficient . IV iron sucrose substitutes iron loss in blood donors more efficiently compared with oral iron sulphate , especially in women . Iron substitution to blood donors should be individualized and based on P-ferritin monitoring OBJECTIVE The aim of this study was to ascertain whether high-dose intravenous ( IV ) iron sucrose could improve symptoms and change brain iron concentrations in idiopathic RLS . METHODS The study was a r and omized , parallel-group double-blind study of 1000 mg iron sucrose given IV versus placebo . Primary measures of the clinical status were global rating scale ( GRS ) and periodic leg movements of sleep ( PLMS ) . Primary measures of brain iron status were CSF ferritin and MRI-determined iron in the substantia nigra . RESULTS At the time of the interim analysis there were 7 placebo and 11 iron-treated subjects . At 2-weeks post-treatment , iron treatment result ed in a small but significant increase in CSF ferritin and a decrease in RLS severity ( GRS ) but did not change PLMS or MRI iron index . None of the secondary outcomes changed with treatment . There was no single case of clear treatment benefit in any of the patients . This interim analysis revealed an effect size that was too small to allow for adequate power to find significant differences with the planed 36-subject enrollment for either the primary objective outcome of PLMS or any of the secondary outcomes . The study was stopped at this planned break-point given the lack of both adequate power and any indication for clinical ly significant benefit . CONCLUSIONS High-dose IV iron failed to demonstrate the robust changes reported in three prior open-label studies . Differences in iron formulation , dosing regiment , and peripheral iron status may explain some of the discrepancies between this and previous IV iron treatment studies Background Absolute iron deficiency , irrespective of aetiology , remains a major and worldwide cause of morbidity . After correction of the causative lesion , reconstitution of haemoglobin level and body iron stores is traditionally achieved with oral administration of ferrous salts . The latter have significant gastrointestinal tract side-effects that , in the short-term , may impair compliance . With protracted administration these products can cause lipid peroxidation which , in turn , may accelerate atherogenesis . An alternative formulation is an iron polymaltose complex where animal data supported a promoting effect of glycerophosphate . Setting and Trial Design This was a single-centre , open , r and omised , multidose four treatment parallel group study . A st and ard dose of ferric polymaltose complex with two differing levels of glycerophosphate was compared with an equivalent amount of iron supplied as ferrous sulphate in anaemic volunteer blood donors . The endpoints were rate of haemoglobin rise and re-expansion of body iron stores reflected in blood ferritin concentration , as well as percentage saturation of transferrin . Secondary observations were changes in the proportion of hypochromic red cells during the course of treatment , erythropoietin levels and tolerability of the two formulations . Results Outcome in the rat model suggested that the utilisation of iron from polymaltose might be enhanced by glycerophosphate . However , in donors this difference was not evident and , accordingly , the data from the three polymaltose groups combined and compared to those receiving ferrous sulphate . The rate at which haemoglobin level improved , red cell indices returned to normal , and the number of hypochromic and microcytic red cells fell was not significantly different between the groups . Similarly the serum iron , percentage saturation of transferrin and red cell ferritin were comparable . In contrast the serum ferritin levels were higher for those receiving ferrous sulphate . Additionally , side-effects were significantly more frequently encountered with the latter preparation . Conclusion These data demonstrate that the addition of glycerophosphate , observed to be beneficial in rats , did not occur in humans . Secondly , in the blood donors , equivalent amounts of iron provided as the polymaltose , with or without glycerophosphate or ferrous sulphate , corrected haemoglobin concentration and morphologically abnormal erythropoiesis at comparable rates . Similarly iron stores are replenished to an equivalent extent as seen in the matching percentage saturation of transferrin and red cell ferritin levels . Interestingly , there is a discrepancy in the serum ferritin which is higher with the salt and this may reflect oxidative stress . Thirdly , corresponding efficacy can be achieved with better patient tolerance for the complex . Finally it is postulated that the iron polymaltose complex formulation more closely approximates the way in which enterocytes h and le dietary iron and thus physiologic regulatory mechanisms would be expected to reciprocally slow down absorption as stores exp and . Logically , therefore and , if confirmed , the latter finding suggests that this formulation may have a potential role in longer-term supplementation programmes BACKGROUND A considerable number of regular blood donors develops an iron deficiency , and the exact amount of iron required to compensate for the iron loss from whole-blood donation in males and females is still unknown . STUDY DESIGN AND METHODS A total of 526 regular blood donors ( 289 male and 237 female ) were r and omly assigned to treatment with either 40 mg , 20 mg , or 0 mg per day of elemental iron as ferrous gluconate for a period of 6 months , during which one unit of whole blood was collected on four occasions ( males ) or three occasions ( females ) . Hemoglobin level , serum ferritin , and soluble transferrin receptor levels were measured before each donation . RESULTS Daily doses of either 40 mg or 20 mg of elemental iron adequately compensated for iron loss in males , who gave blood at 2-month intervals , but did not result in a positive iron balance or an increase in storage iron as reflected by the logarithm of the ratio of transferrin receptor to ferritin concentration . In females , who donated at 3-month intervals , the same daily doses not only restored the iron balance but also led to an increase in storage iron . The number of gastrointestinal side effects due to iron supplementation ( 12 % ) was only slightly higher in both iron groups than in the placebo group . CONCLUSION The results of this study indicate that 20 mg of elemental iron per day can adequately compensate for iron loss in males and females who donate whole blood up to four ( females ) or six times per year ( males ) Seven hundred seventeen healthy male blood donors regularly donating four or more units a year were surveyed for haemoglobin and serum ferritin levels . One hundred fiftyone ( 21 % ) had a haemoglobin less than 13.5 g/dl and were therefore disqualified from further blood donation , having a mean serum ferritin of 28 μg/liter . Of the remaining 566 donors with haemoglobin levels equal to or greater than 13.5 g/dl , the mean serum ferritin was 33 μg/liter , although in 299 ( 53 % ) the value was less than 28 μg/liter . To document response to iron therapy 46 donors with haemoglobin levels equal to or greater than 13.5 g/dl were stratified into those with the lowest iron stores ( group 1 ; n = 23 ) , defined as a serum ferritin less than 20 μg/liter , and controls ( group 2 ; n = 23 ) , with serum ferritin between 50 and 150 μg/liter . Within each stratum donors r and omly received ferric polymaltose at a dose of 100 mg elemental iron twice daily for 56 days ( groups 1a and 2a ) or an identical iron‐free placebo tablet administered on the same schedule ( groups 1b and 2b ) . Iron therapy in the iron‐deficient group ( group 1a : n = 11 ) result ed in a significant rise in haemoglobin ( p = .03 ) and iron stores reflected in serum ferritin ( p = .002 ) compared to those receiving placebo ( group 1b ) . In the control group iron therapy or placebo was without significant effect . Thus , ferric polymaltose preparation is bioavailable and is notable for the virtual absence of gastrointestinal tract side effects Depletion of body iron stores is a major factor limiting regular blood donations by menstruating females . To determine if regular iron supplementation would solve this problem , we conducted a double-blind study in which menstruating female donors were r and omly placed into one of three groups : one taking 39 mg elemental iron , a second taking 39 mg of iron plus 75 mg vitamin C , and a third taking 100 mg vitamin C daily . The women were requested to donate every 8 weeks for at least 1 year . Blood sample s were taken on each donation for measurements of hemoglobin , total iron binding capacity ( TIBC ) , and ferritin . In the two groups taking iron supplements hemoglobin and ferritin increased from baseline values and the TIBC decreased . The vitamin C control group showed decreases from baseline for hemoglobin and ferritin and increases in TIBC . Differences between groups taking iron supplements and the group not taking supplements were highly significant . Drop-out from the study was due to various causes ; however , iron intolerance was uncommon . Minimal daily iron supplementation was beneficial in maintaining body iron stores and hemoglobin levels in menstruating females on a schedule of blood donation as often as every 8 weeks BACKGROUND Anaemia caused by iron deficiency is common in children younger than age 5 years in eastern Africa . However , there is concern that universal supplementation of children with iron and folic acid in areas of high malaria transmission might be harmful . METHODS We did a r and omised , placebo-controlled trial , of children aged 1 - 35 months and living in Pemba , Zanzibar . We assigned children to daily oral supplementation with : iron ( 12.5 mg ) and folic acid ( 50 mug ; n=7950 ) , iron , folic acid , and zinc ( n=8120 ) , or placebo ( n=8006 ) ; children aged 1 - 11 months received half the dose . Our primary endpoints were all-cause mortality and admission to hospital . Analyses were by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N59549825 . FINDINGS The iron and folic acid-containing groups of the trial were stopped early on Aug 19 , 2003 , on the recommendation of the data and safety monitoring board . To this date , 24 076 children contributed a follow-up of 25,524 child-years . Those who received iron and folic acid with or without zinc were 12 % ( 95 % CI 2 - 23 , p=0.02 ) more likely to die or need treatment in hospital for an adverse event and 11 % ( 1 - 23 % , p=0.03 ) more likely to be admitted to hospital ; there were also 15 % ( -7 to 41 , p=0.19 ) more deaths in these groups . INTERPRETATION Routine supplementation with iron and folic acid in preschool children in a population with high rates of malaria can result in an increased risk of severe illness and death . In the presence of an active programme to detect and treat malaria and other infections , iron-deficient and anaemic children can benefit from supplementation . However , supplementation of those who are not iron deficient might be harmful . As such , current guidelines for universal supplementation with iron and folic acid should be revised BACKGROUND Iron deficiency leading to low hemoglobin concentration ( cHb ) is a common problem for blood donors as well as for blood banks . A st and ardized protocol offering iron supplementation based on P-ferritin determination may help to reduce the problem and retain donors . STUDY DESIGN AND METHODS This was a prospect i ve study where 879 blood donors , presenting with cHb at or below the limit of acceptance for donation , were included . The predonation cHb result was read after donation . The donors received 50 iron tablets ( JernC or Ferrochel , 100 or 25 mg elemental iron , respectively ) , and sample s for P-ferritin , mean corpuscular volume , and control of cHb were secured . Based on a P-ferritin level of less than 60 microg per L , 20 iron tablets were offered after all following donations . RESULTS Mean cHb was 7.6 mmol per L ( 122 g/L ) and 8.2 mmol per L ( 132 g/L ) in women and men , respectively . In 80 percent of the women and 48 percent of the men , iron stores were low ( P-ferritin < or = 30 microg/L ) . In the donors returning once or twice , an increase in cHb and P-ferritin was seen . Fifteen donors were permanently deferred due to disease and 36 due to low cHb , but 2 years after the start of the study , 79 percent of the women and 85 percent of the men were still active donors . CONCLUSION A st and ardized protocol offering iron supplementation and simple oral and written advice based on P-ferritin measurements is effective in normalizing cHb and retaining donors presenting with cHb at or below the limit of acceptance for donation A series of 58 male blood donors has been studied with regard to stainable bone marrow iron , desferrioxamine test , sideroblasts , total iron-binding capacity , serum iron , and haemoglobin values . With one conventional blood donation every second month the storage iron was found to be significantly decreased after four blood donations both when placebo and oral ferrous iron in doses of up to 2000 mg were given over a period of two weeks after each blood-letting . The iron state in donors given 2000 mg was superior to that in donors given 1000 mg , and better in the latter group than when placebo was given . A moderate increase in the total iron-binding capacity could be discerned in subjects treated with placebo or only 1000 mg iron after each donation , but no changes in serum iron or haemoglobin were noted . A smaller series of 13 donors was also investigated after six donations and was found to show essentially the same pattern in the iron state variables as after four donations . When the interval between donations was four months and 2000 mg ferrous iron was given over two weeks after each donation , all variables including the amount of bone marrow iron and the desferrioxamine test remained unchanged in ten subjects after four donations . Two subjects showed a moderate decrease in the stainable bone marrow iron , but it did not disappear completely BACKGROUND Iron deficiency is a public problem in women , which contributes to the high percentage of deferred blood donations in this group . This study evaluated the effect of iron supplementation in improving iron stores to promote safe blood donation in women . STUDY DESIGN AND METHODS A total of 412 female blood donors were r and omly recruited for the study . The volunteers were scheduled for an initial visit and three subsequent visits at 4-month intervals for possible repeat donation . Each volunteer was given 21 tablets of 150 mg of ferrous sulfate or placebo to be taken three times daily for 1 week after each blood donation . Their hemoglobin ( Hb ) concentration , hematocrit ( Hct ) , serum ferritin , total iron-binding capacity ( TIBC ) , and percent saturation of the TIBC were tested throughout the course of the study . RESULTS The group taking ferrous sulfate showed no significant difference between the mean initial and final result for any of the values other than Hb values , whereas there was a significant decline in mean Hb , Hct , serum iron , serum ferritin , and percent saturation in the group taking placebo . Hb concentrations declined significantly in both groups ; however , it was more severe in the placebo group when compared to the ferrous sulfate group . The relative risk of iron deficiency in placebo group was 3.6 ( 95 % confidence interval = 1.73 - 7.74 ) . CONCLUSION The results indicate that supplementation therapy can be considered as one of the strategies to promote safe blood donation in women . A quantity of 150 mg of elemental iron per day as ferrous sulfate , however , is not the correct dose for Iranian female donors Iron deficiency may exacerbate symptoms in the Restless Legs Syndrome ( RLS ) . We investigated the effect of intravenous iron sucrose or placebo on symptoms in patients with RLS and mild to moderate iron deficit . Sixty patients with primary RLS ( seven males , age 46 ( 9 ) years , S-ferritin < or = 45 microg/L ) recruited from a cohort of 231 patients were r and omly assigned in a 12-months double-blind , multi-centre study of iron sucrose 1000 mg ( n = 29 ) or saline ( n = 31 ) . The primary efficacy variable was the RLS severity scale ( IRLS ) score at week 11 . Median IRLS score decreased from 24 to 7 ( week 11 ) after iron sucrose and from 26 to 17 after placebo ( P = 0.123 , N.S. for between treatment comparison ) . The corresponding scores at week 7 were 12 and 20 in the two groups ( P = 0.017 ) . Drop out rate because of lack of efficacy at 12 months was 19/31 after placebo and 5/29 patients after iron sucrose ( Kaplan-Meier estimate , log rank test P = 0.0006 ) suggesting an iron induced superior long term RLS symptom control . Iron sucrose was well tolerated . This study showed a lack of superiority of iron sucrose at 11 weeks but found evidence that iron sucrose reduced RLS symptoms both in the acute phase ( 7 weeks ) and during long-term follow up in patients with variable degree of iron deficiency . Further studies on target patient groups , dosing and dosing intervals are warranted before iron sucrose could be considered for treatment of iron deficient patients with RLS Serum ferritin levels were determined in 170 healthy Norwegian women ( 18 - 48 y , median age 36 y ) including 23 blood donors . Exhausted iron stores , defined by serum ferritin levels less than 17 micrograms/l , were found in 21.8 % of the non-donors , and in 30.4 % of the donors . Women with serum ferritin levels less than or equal to 20 micrograms/l participated in a bioavailability study . They were r and omized to one of three groups and given one of three different low dose iron supplements ( 18 - 20 mg iron per day ) for six months . One of the supplements contained heme iron and non-heme iron , the other two contained non-heme iron only . Mean serum ferritin increase was significant for two of the supplements , the one containing heme iron giving the best result . All the supplements result ed in a significant decrease in TIBC A r and omized , double-blind trial of iron replacement after repeated blood donation was conducted in 75 menstruating women ; 51 completed the study . Volunteers were assigned r and omly to one of three treatment groups : 1 ) carbonyl iron ( nontoxic elemental iron powder ) , 600 mg ; 2 ) ferrous sulfate , 300 mg ( 60 mg Fe++ ) ; or 3 ) placebo , each given three times daily for 1 week immediately after blood donation . Blood sample s obtained initially and 56 days later were tested for hemoglobin , mean corpuscular volume ( MCV ) , free erythrocyte protoporphyrin , serum ferritin , serum iron , total iron binding capacity ( TIBC ) , and percent saturation of TIBC . The prevalence of gastrointestinal side effects was similar in both groups taking iron . At the end of the study there was no laboratory evidence of change in iron status in women who received carbonyl iron ( n = 15 ) . In those treated with ferrous sulfate ( n = 17 ) the mean TIBC increased ( p less than 0.001 ) , and in the placebo group ( n = 19 ) there were decreases in mean MCV ( p less than 0.01 ) , serum ferritin ( p less than 0.001 ) , and percent saturation ( p = 0.027 ) with an increase in mean TIBC ( p = 0.004 ) . Carbonyl iron seems to be effective for short-term iron replacement in repeat blood donors and may have the advantage of decreased or absent risk of poisoning if accidentally ingested by children INTRODUCTION Frequent blood donations may lead to a negative iron balance . Iron depletion may be prevented by iron supplementation after whole blood donations . The aim of this study was to compare the short time changes in iron status after donation in two groups r and omized to iron supplementation or no additional iron . A second objective was to evaluate the effect of iron supplementation in donors having HFE-variants compared to HFE wild types . METHODS Subjects of both genders ( 199 women , 200 men ) were r and omised to receive iron supplementation or no additional iron after donation . Iron status , defined by the concentration of haemoglobin , serum ferritin , soluble transferrin receptor , concentration of haemoglobin in reticulocytes ( CHr ) and percent hypochrome mature red blood cells , was determined at the start of donation and 8 + /- 2 days after donation . HFE genotyping was performed at reappearance . RESULTS There was a significant difference between the two study groups on all the iron status parameters . CHr was an efficient , early marker of ongoing synthesis of haemoglobin . Heterozygosity for the HFE variants C282Y and H63D had no statistically significant influence on the iron status . The donor 's baseline serum ferritin value may be basis for an individual iron supplementation regimen , as donors with serum ferritin > 50 microg/l do not seem to utilize the iron supplementation , but prefer endogenous iron to restore the loss of haemoglobin . CONCLUSION Iron supplementation had a significant positive impact on the restoration of iron status one week after donation . The absorption of iron from a sustained release preparation given in a dose of 100 mg ferrous iron twice daily ( at breakfast and at dinner or bedtime ) has been compared to the absorption from a rapidly disintegrating ferrous sulphate tablet given in a dose of 50 mg iron 4 times daily ( at breakfast , lunch , dinner and bedtime ) . The studies were performed in 34 subjects—20 blood donors and 14 patients with iron deficiency anemia . In blood donors the same amount of iron was absorbed from the two types of medication . In patients with iron deficiency anemia significantly more iron was absorbed from the sustained release preparation . There was no indication that the time of intake of the second daily dose of the sustained release preparation had any significant influence on the absorption A blind r and omized trial was conducted in a low-income community in the city of Recife , Pernambuco , Brazil , with 193 anemic ( Hb < 12 mg/dl ) and " menstruating " women ( age range : 15 - 45 years ) to compare daily and weekly doses of ferrous sulfate ( 60 mg elemental iron ) and treatment compliance . Blood sample s were taken from 484 women to determine hemoglobin levels before and after the trial and mean corpuscular volume ( MCV ) at end of treatment . After 12 weeks ' follow-up , 150 women completed the trial , 79 on the alternative weekly regimen and 71 on the conventional daily regimen . Mean corpuscular hemoglobin concentrations ( MCHC ) prior to treatment were 10.52 g/dl ( DP=1.13 ) and 10.72 g/dl ( DP=0.92 ) , respectively , for the alternative and conventional regimens . After the intervention they were 11.83 g/dl ( DP=0.97 ) for the weekly regimen and 11.62 g/dl ( DP=1.39 ) for the daily one . The alternative regimen was better accepted than the conventional one . There was no significant difference ( p=0.22 ) between differences in the mean values of the two regimens , although the cure rate was higher after the alternative treatment . The study concluded that the weekly regimen was no less effective than daily treatment The side-effects of a new sustained release oral ferrous sulphate preparation have been evaluated in three separate double-blind studies . Each tablet contained 100 mg of ferrous iron and the dosage employed in all studies was 2 tablets daily . In a large series of blood donors r and omly divided into three groups the frequency and type of side-effects were compared to ferrous sulphate tablets and placebo . In two series of pregnant women the side-effects were studied with a cross-over technique using ferrous sulphate tablets as reference . Placebo was also included as a reference in one of these studies . In all series the frequency of nausea and epigastric pain was about the same for the sustained release preparation as for placebo . In all series ferrous sulphate tablets gave a significantly higher frequency of nausea than the sustained release tablets and placebo . Also the frequency of epigastric pain was found to be higher in blood donors but this could not be verified in pregnant women BACKGROUND Iron deficiency anemia has occurred more frequently in female than male regular blood donors . Iron supplement is necessary for maintaining the hemoglobin level . A combination with ascorbic acid increases the absorption of iron . OBJECTIVE Compare the effect of ferrous fumarate 200 mg/day and the combination of ferrous fumarate 200 mg/day with ascorbic acid 100 mg/day and 500 mg/day on hemoglobin level and red blood cell indices in female regular blood donors . MATERIAL AND METHOD Female regular blood donor volunteers were r and omly divided into three equal groups to supplement with each regimen for one month . Hemoglobin ( Hb ) , MCV , MCH , and MCHC before and after blood donation at 0.5 , 1 , 2 , and 3 months , were compared . RESULTS Ninety-six volunteers were included and equally divided into three groups of 32 volunteers each . There were no significant differences between age , BMI , ABO blood group , Rh , Hb , MC , MCH , and MCHC before blood donation between each group ( p > 0.05 ) . The duration of recovery times of Hb to before blood donation levels in group I , II , and III being 2 , 3 , and 1 month , respectively were statistically significant difference ( p < 0.001 ) . The duration of recovery times of MCV , MCH , and MCHC to before blood donation levels in both group II and III were similar ( 0.5 months in every value ) , which was more rapid than in group I ( > 3 , 3 , and 1 month , respectively ) with statistically significant difference ( p < 0.001 ) . All three groups tolerated well . No participant withdrew from the present study because of side effects . CONCLUSION The present study shows that a combination of ferrous fumarate 200 mg and ascorbic acid 500 mg per day accelerates timing of hemoglobin and red blood cell indices in recovery to the level of before blood donation in female regular blood donors Female blood donors with low hematocrit levels detected by copper sulfate screening were selected r and omly to receive either 75 mg of iron per day , as ferrous gluconate , or a calcium phosphate placebo . Their ferritin , serum iron , total iron-binding capacity , zinc protoporphyrin , and hemoglobin values , as well as their suitability to donate blood , were determined initially ( Visit 1 ) and at four follow-up visits ( Visits 2 - 5 ) . By the second visit , the serum ferritin and iron values of donors receiving iron supplementation differed significantly from those of donors receiving placebo . By the fifth visit , a less marked but significant increase in hemoglobin had occurred in the iron group , but not in the placebo group . At no time was there a significant difference between the groups ' suitability to donate blood , with each group donating at almost half of their visits . The authors conclude that iron supplementation at this dose level in deferred female blood donors improves their iron status and hemoglobin levels , but does not significantly increase their suitability to donate blood as compared with the suitability of placebo-treated donors The effectiveness of elemental , nontoxic carbonyl iron in replacing iron lost at blood donation was examined . In a r and omized double-blind design , 99 women , aged 18 to 40 , were given placebo or low-dose carbonyl iron ( 100 mg orally ) at bedtime for 56 days after phlebotomy . Compliance was equivalent for the two regimens . Mild side effects were slightly greater with carbonyl iron . At Day 56 , estimated net iron absorption from therapy or diet , or both , was sufficient to replace iron in 85 percent of those receiving carbonyl iron but in only 29 percent of those taking placebo ( p less than 0.001 ) . The rates of deferral from repeat donation were 8 percent in the carbonyl iron group and 36 percent in the placebo group ( p less than 0.01 ) , and the positive predictive value of routine screening in identifying participants without iron deficiency was 83 versus 13 percent ( p less than 0.01 ) . It can be concluded that short-term carbonyl iron supplementation in female blood donors can replace the iron lost at phlebotomy , protect the women against iron deficiency , and enhance their ability to give blood Summary Background Bioavailability data in humans of elemental iron powders is limited although elemental iron is a common form of iron when used as a fortificant . Aim of the study The relative bioavailability ( RBV ) of seven elemental iron powders , five commercially available and two developmental are evaluated . In addition , one commercial electrolytic iron powder given with ascorbic acid ( AA ) was examined . Methods Based on a vali date d method this double – blinded r and omized crossover study included three groups of male blood donors ( n = 3 * 16 ) who were served rolls fortified with different elemental iron powders or ferrous sulfate ( FeSO4 ) nine weeks apart . Blood sample s were drawn every hour for six hours . RBV was obtained by comparing the increase in serum iron concentration induced by the elemental iron with the increase induced by FeSO4 . Results All elemental iron powders studied were significantly less well absorbed compared to FeSO4 . The electrolytic iron given with 50–mg AA was as well absorbed as FeSO4 ( molar ratio = 1:6 , AA : Fe ) . The mean RBVs of the iron powders were : electrolytic ( A–131 , RBV = 0.65 ) ; electrolytic ( Electrolytic , RBV = 0.59 ) ; carbonyl ( Ferronyl , RBV = 0.58 ) ; H – reduced ( AC– 325 , RBV = 0.56 ) ; H – reduced ( Hi – Sol , RBV = 0.50 ) ; carbonyl ( CF , RBV = 0.37 ) ; reduced ( Atomet 95SP , RBV = 0.36 ) . The reduced iron was distinguished by having significantly lower RBV ( 0.36 ) although no significant overall ranking was possible . Conclusion Based on a vali date d method this doubleblinded cross – over study in humans showed that the evaluated elemental iron powders currently available for commercial use are significantly less well absorbed compared to FeSO4 . The results indicate that the reduced iron powder was absorbed to a lower extent compared to the other iron powders and only 36 % compared to FeSO4 . Ascorbic acid seems to improve the bioavailability of elemental iron even though a rather low molar ratio is used . Thus , if confirmed , this enhancing effect of ascorbic acid on elemental iron when used as a fortificant could be used by co – fortifying them Abstract : 49 female blood donors with iron‐deficiency anemia were treated with equal doses of iron either as carbonyl iron or ferrous sulfate in a r and omized , double‐blind fashion . The prevalence of side‐effects was similar in the two groups . Mean values for hemoglobin concentration , mean corpuscular volume , corrected reticulocyte count , platelet count , serum iron , total iron‐binding capacity , transferrin saturation or erythrocyte proto‐porphyrin did not differ significantly between the two groups throughout the study . After 16 weeks of therapy , the mean increase in hemoglobin iron was similar in both groups ( p = 0.2 ) . Estimates of net changes in total body iron suggested that the overall bioavailability of carbonyl iron was high , about 70 % that of ferrous sulfate BACKGROUND The benefits of 2-unit red blood cell ( RBC ) apheresis are evident , but iron depletion may be a limiting factor in using this technology . Regular iron supplementation may allow a better utilization of this technique . STUDY DESIGN AND METHODS In this study , 260 regular blood donors donated 2-unit RBCs on each of a total of seven visits at intervals of 8 to 10 weeks . The volunteers were r and omly assigned to receive 100 mg of iron(II ) or placebo daily . Group A received iron capsules after the first three donations , and Group B after the second three donations , respectively . Hemoglobin , serum ferritin , and serum iron were measured before each donation . RESULTS Mean serum ferritin concentration decreased after each donation in the placebo phase of both treatment groups , but it remained largely constant during the iron phase in Group A , and even increased during the iron phase in Group B. CONCLUSION Regular iron supplementation prevents iron depletion in the majority of donors after 2-unit RBC apheresis within an 8- to 10-week period Iron protein succinylate is a new iron preparation for oral administration . In a controlled study versus iron sulphate in 40 blood donors with low levels of stored iron , treatment for 30 days with iron protein succinylate result ed in greater iron absorption compared to the reference drug . Serum iron concentration significantly increased compared with baseline values only in patients given iron protein succinylate . The amount of stored iron , evaluated by serum ferritin levels , significantly increased in both treatment groups . , accepted 15 October |
2,272 | 32,010,404 | : This study confirmed PTEN loss is an important independent factor for breast cancer prognosis | AIM : This study aims to determine the prognostic significance of phosphatase and tensin homolog ( PTEN ) loss in breast cancer . | Introduction Inhibitors of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin ( PI3K/AKT/mTOR ) pathway can overcome endocrine resistance in estrogen receptor ( ER ) α-positive breast cancer , but companion diagnostics indicating PI3K/AKT/mTOR activation and consequently endocrine resistance are lacking . PIK3CA mutations frequently occur in ERα-positive breast cancer and result in PI3K/AKT/mTOR activation in vitro . Nevertheless , the prognostic and treatment-predictive value of these mutations in ERα-positive breast cancer is contradictive . We tested the clinical validity of PIK3CA mutations and other canonic pathway drivers to predict intrinsic resistance to adjuvant tamoxifen . In addition , we tested the association between these drivers and downstream activated proteins . Methods Primary tumors from 563 ERα-positive postmenopausal patients , r and omized between adjuvant tamoxifen ( 1 to 3 years ) versus observation were recollected . PIK3CA hotspot mutations in exon 9 and exon 20 were assessed with Sequenom Mass Spectometry . Immunohistochemistry was performed for human epidermal growth factor receptor 2 ( HER2 ) , phosphatase and tensin homolog ( PTEN ) , and insulin-like growth factor 1 receptor ( IGF-1R ) . We tested the association between these molecular alterations and downstream activated proteins ( like phospho-protein kinase B ( p-AKT ) , phospho-mammalian target of rapamycin ( p-mTOR ) , p-ERK1/2 , and p-p70S6 K ) . Recurrence-free interval improvement with tamoxifen versus control was assessed according to the presence or absence of canonic pathway drivers , by using Cox proportional hazard models , including a test for interaction . Results PIK3CA mutations ( both exon 9 and exon 20 ) were associated with low tumor grade . An enrichment of PIK3CA exon 20 mutations was observed in progesterone receptor- positive tumors . PIK3CA exon 20 mutations were not associated with downstream-activated proteins . No significant interaction between PIK3CA mutations or any of the other canonic pathway drivers and tamoxifen-treatment benefit was found . Conclusion PIK3CA mutations do not have clinical validity to predict intrinsic resistance to adjuvant tamoxifen and may therefore be unsuitable as companion diagnostic for PI3K/AKT/mTOR inhibitors in ERα- positive , postmenopausal , early breast cancer patients Background African-American women have higher mortality from breast cancer than other ethnic groups . The association between poor survival and differences with tumor phenotypes is not well understood . The purpose of this study is to assess the clinical significance of ( 1 ) Stem cell-like markers CD44 and CD24 ; ( 2 ) PI3K/Akt pathway associated targets PTEN , activation of Akt , and FOXO1 ; and ( 3 ) the Insulin-like growth factor-1 ( IGF-I ) and IGF binding protein-3 ( IGFBP3 ) in different breast cancer subtypes , and compare the differences between African-American and Hispanic/Latina women who have similar social-economic-status . Methods A total of N=318 African-American and Hispanic/Latina women , with clinical ly-annotated information within the inclusion criteria were included . Formalin fixed paraffin embedded tissues from these patients were tested for the different markers using immunohistochemistry techniques . Kaplan-Meier survival-curves and Cox-regression analyses were used to assess Relative Risk and Disease-Free-Survival ( DFS ) . Results The triple-negative-breast-cancer ( TNBC ) receptor-subtype was more prevalent among premenopausal women , and the Hormonal Receptor ( HR ) positive subtype was most common overall . TNBC tumors were more likely to have loss of PTEN , express high Ki67 , and have increased CD44+/CD24- expression . TNBC was also associated with higher plasma-IGF-I levels . HR-/HER2 + tumors showed high pAkt , decreased FOXO1 , and high CD24 + expression . The loss of PTEN impacted DFS significantly in African Americans , but not in Hispanics/Latinas after adjusted for treatment and other tumor pathological factors . The CD44+/CD24- and CD24+/CD44- phenotypes decreased DFS , but were not independent predictors for DFS . HER2-positive and TNBC type of cancers continued to exhibit significant decrease in DFS after adjusting for the selected biomarkers and treatment . Conclusions TNBC incidence is high among African-American and Hispanic/Latino women residing in South Los Angeles . Our study also shows for the first time that TNBC was significantly associated with PTEN loss , high Ki67 and the CD44+/CD24- phenotype . The loss of PTEN impacts DFS significantly in African Americans Introduction Worldwide , many patients with HER2 + ( human epidermal growth factor receptor 2-positive ) early breast cancer ( BC ) do not receive adjuvant trastuzumab . Hazards of recurrence of these patients with respect to hormone receptor status of the primary tumor have not been described . Methods Using data from 1,260 patients r and omized to placebo in the adjuvant TEACH trial , we report 10-year annual hazards of recurrence in HER2 + patients not treated with anti-HER2 therapy . Results Disease-free survival ( DFS ) was 75 % after 5 and 61 % after 10 years , respectively . Patients with HER2 + hormone receptor-positive ( HR+ ( hormone receptor-positive ) ; ER+ ( estrogen receptor-positive ) or PR+ ( progesterone receptor-positive ) ) disease had a significantly better DFS than patients with HER2 + HR- ( ER-/PR- ) disease ( hazard ratio 0.72 , P = 0.02 ) . This difference was explainable by a significantly higher hazard of recurrence in years 1 to 5 in HER2 + HR- compared to HER2 + HR+ patients , with a mean risk of recurrence of 9%/year for HR- versus 5%/year in HR+ patients ( hazard ratio 0.59 , P = 0.002 for years 1 to 5 ) . The high early risk of recurrence of HER2 + HR- patients declined sharply over time , so that it was similar to that seen in HER2 + HR+ patients in years 6 to 10 ( hazard ratio 0.97 , P = 0.92 for years 6 to 10 ) . Conclusions Our results show that outcomes in HER2 + patients with early BC not receiving anti-HER2 therapy strongly depend on HR expression . The very high early risk of relapse seen in HER2 + HR- patients is particularly relevant in health care setting s with limited access to adjuvant anti-HER2 treatment . The event rates shown for sub population s of HER2 + BC patients suggest that in re source -constrained environments patients with HER2 + HR- early BC should be prioritized for consideration of adjuvant anti-HER2 therapy PURPOSE It has been suggested that PTEN , a negative regulator of PI3K/AKT signaling , is involved in tumor sensitivity to trastuzumab . We investigated the association between tumor PTEN protein expression and disease-free survival ( DFS ) of patients r and omly assigned to receive chemotherapy alone ( arm A ) or chemotherapy with sequential ( arm B ) or concurrent trastuzumab ( arm C ) in the phase III early-stage human epidermal growth factor receptor 2 ( HER2 ) -positive trial-North Central Cancer Treatment Group ( NCCTG ) N9831 . PATIENTS AND METHODS The intensity and percentage of invasive cells with cytoplasmic PTEN staining were determined in tissue microarray sections containing three cores per block ( n = 1,286 ) or in whole tissue sections ( WS ; n = 516 ) by using st and ard immunohistochemistry ( 138G6 monoclonal antibody ) . Tumors were considered positive for PTEN ( PTEN-positive ) if any core or WS had any invasive cells with ≥ 1 + staining . Median follow-up was 6.0 years . RESULTS Of 1,802 patients included in this analysis ( of 3,505 patients registered to N9831 ) , 1,342 ( 74 % ) had PTEN-positive tumors . PTEN positivity was associated with hormone receptor negativity ( χ(2 ) P < .001 ) and nodal positivity ( χ(2 ) P = .04 ) . PTEN did not have an impact on DFS within the various arms . Comparing DFS of arm C to arm A , patients with PTEN-positive and PTEN-negative tumors had hazard ratios ( HRs ) of 0.65 ( P = .003 ) and 0.47 ( P = .005 ) , respectively ( interaction P = .16 ) . For arm B versus arm A , patients with PTEN-positive and PTEN-negative tumors had HRs of 0.70 ( P = .009 ) and 0.85 ( P = .44 ) , respectively ( interaction P = .47 ) . CONCLUSION In contrast to selected pre clinical and limited clinical studies suggesting a decrease in trastuzumab sensitivity in patients with PTEN-negative tumors , our data show benefit of adjuvant trastuzumab for patients with HER2-positive breast cancer , independent of tumor PTEN status |
2,273 | 28,105,573 | Strength gains between conditions were not influenced by training status and age .
Conclusions Overall , the results suggest that fast and moderate-slow resistance training improve dynamic muscular strength similarly in individuals within a wide range of training statuses and ages .
Resistance training performed at fast movement velocities using moderate intensities showed a trend for superior muscular strength gains as compared to moderate-slow resistance training . | Background Movement velocity is an acute resistance-training variable that can be manipulated to potentially optimize dynamic muscular strength development .
However , it is unclear whether performing faster or slower repetitions actually influences dynamic muscular strength gains .
Objective We conducted a systematic review and meta- analysis to examine the effect of movement velocity during resistance training on dynamic muscular strength . | PURPOSE Athletes often use weight training to prepare for sprint events , but the effectiveness of different types of weight training for sprinting is unclear . We have therefore investigated the effect of slow and explosive weight training on kayak sprint performance . METHODS Twenty-seven male and 11 female experienced sprint kayakers were r and omized to slow weight training , explosive weight training , or control ( usual training ) groups . Weight training consisted of two sessions per week for 6 wk ; in each session the athletes performed 3 - 4 sets of two sport-specific exercises with a load of 80 % 1-repetition-maximum . The two training programs differed only in the time taken to complete the concentric phase of the exercises : slow , 1.7 s ; explosive , < 0.85 s. To determine the effects of training on sprint acceleration and speed maintenance , the athletes performed 15-m kayaking sprints pre- and posttraining ; an electronic timing system provided sprint times at 3.75- , 7.5- , and 15-m marks . RESULTS Relative to control , both types of weight training substantially improved strength and sprint performance . The improvements in mean sprint time over 15 m in each group were : slow , 3.4 % ; explosive , 2.3 % ; control , -0.2 % ( 90 % confidence limits for pairwise differences , approximately + /-1.4 % ) . Over the first 3.75 m , the improvements were : slow , 7.1 % ; explosive , 3.2 % ; control , 1.4 % ( approximately + /-2.6 % ) . Over the last 7.5 m , the improvements were : slow , 2.1 % ; explosive , 3.0 % ; control , -0.8 % ( approximately + /-1.9 % ) . CONCLUSIONS Slow weight training is likely to be more effective than explosive training for improving the acceleration phase of sprinting , when force is high throughout the length of the stroke . Explosive weight training may be more effective in speed maintenance , when forces are developed rapidly over a short period at the start of the stroke Sayers , SP and Gibson , K. A comparison of high-speed power training and traditional slow-speed resistance training in older men and women . J Strength Cond Res 24(12 ) : 3369 - 3380 , 2010-Muscle power , the product of force × velocity , is a critical determinant of function in older adults . Resistance training ( RT ) at high speed has been shown to improve peak muscle power in this population ; however , different functional tasks may benefit from the improvement of power at values other than “ peak ” values , for example , tasks that require a greater velocity component or a greater force component . This study compared the effect of high-speed RT on muscle performance ( peak power [ PP ] and its components [ PP force and PP velocity ] and overall peak velocity [ VEL ] ) across a broad range of external resistances . Thirty-eight older men and women were r and omized to high-speed power training at 40 % of the 1-repetition maximum ( 1RM ) ( n = 13 [ 74.1 ± 6.4 years ] ) ; traditional RT at 80 % 1RM ( n = 13 [ 70.1 ± 7.0 years ] ) ; or control ( n = 12 [ 72.8 ± 4.1 years ] ) . Measures of muscle performance were obtained at baseline and after the 12-week training intervention . Muscle power and 1RM strength improved similarly with both high-speed and traditional slow-speed RT . However , speed-related muscle performance characteristics , PP velocity and overall VEL , were most positively impacted by high-speed power training , especially at lower external resistances . Because gains in speed-related measures with high-speed training compared to traditional RT do not come at the expense of other muscle performance outcomes , we recommend using an RT protocol in older adults that emphasizes high-speed movements at low external resistances OBJECTIVE To determine the effect of training intensity on the contributions of force and velocity to improvements in peak power ( PP ) after explosive resistance training in older adults . METHODS 112 healthy older adults ( 69 + /- 6 yr ) were r and omized to explosive resistance training at 20 % ( G20 ) , 50 % ( G50 ) , or 80 % ( G80 ) maximal strength ( 1-repetition maximum ) for 8 - 12 wk ( twice weekly , 5 exercises , 3 sets of 8 explosive concentric/slow eccentric repetitions ) using pneumatic resistance machines or a nontraining control group ( CON ) . RESULTS Force at peak power ( FPP ) increased significantly and similarly among training groups compared with CON . Velocity at peak power ( VPP ) did not improve significantly and remained similar between all groups . Force contributed significantly more to PP production in G80 and G50 than in CON . The change in PP was independently predicted by changes in fat-free mass in G80 and by changes in both FPP and VPP in G50 and G20 . CONCLUSION Explosive resistance training in older adults results in the ability to produce higher PP outputs with heavier loads without loss of movement velocity . Moderate- to high-intensity training induced a greater relative contribution of force to PP production in this cohort The purpose of this investigation was to examine the effect of an 8-week training program with heavy- vs. light-load jump squats on various physical performance measures and electromyography ( EMG ) . Twenty-six athletic men with varying levels of resistance training experience performed sessions of jump squats with either 30 % ( JS30 , n = 9 ) or 80 % ( JS80 , n = 10 ) of their one repetition maximum in the squat ( 1RM ) or served as a control ( C , n = 7 ) . An agility test , 20-m sprint , and jump squats with 30 % ( 30J ) , 55 % ( 55J ) , and 80 % ( 80J ) of their 1RM were performed before and after training . Peak force , peak velocity ( PV ) , peak power ( PP ) , jump height , and average EMG ( concentric phase ) were calculated for the jumps . There were significant increases in PP and PV in the 30J , 55J , and 80J for the JS30 group ( p < 0.05 ) . The JS30 group also significantly increased in the 1RM with a trend towards improved 20-m sprint times . In contrast , the JS80 group significantly increased both PF and PP in the 55J and 80J and significantly increased in the 1RM but ran significantly slower in the 20-m sprint . In the 30J the JS30 group 's percentage increase in EMG activity was significantly different from the C group . In the 80J the JS80 group 's percentage increase in EMG activity was significantly different from the C group . This investigation indicates that training with light-load jump squats results in increased movement velocity capabilities and that velocity-specific changes in muscle activity may play a key role in this adaptation The authors investigated the effects of low-intensity resistance training on muscle size and strength in older men and women . Thirty-five participants ( age 59 - 76 yr ) were r and omly assigned to 2 groups and performed low-intensity ( 50 % of 1-repetition maximum ) knee-extension and -flexion exercises with either slow movement and tonic force generation ( LST ; 3-s eccentric , 3-s concentric , and 1-s isometric actions with no rest between repetitions ) or normal speed ( LN ; 1-s concentric and 1-s eccentric actions with 1-s rests between repetitions ) twice a week for 12 wk ( 2-wk preparation and 10-wk intervention ) . The LST significantly increased thigh-muscle thickness , as well as isometric knee-extension and -flexion strength . The LN significantly improved strength , but its hypertrophic effect was limited . These results indicate that even for older individuals , the LST can be an effective method for gaining muscle mass and strength Initial strength gains were examined in the context of learning a new skill . Forty female volunteers were r and omly assigned to one of four groups : a bench-press training group utilizing heavy loads in its training , a bench-press training group utilizing almost no load , an alternative training group using different exercises , or a control group that did not train . Training period was 6 wk , with three training sessions per week . Emphasis was put on keeping the coordination and muscular adaptation dem and s in the bench-press groups as invariant as possible . Bench-press training with a light or with a heavy weight was shown to be equally effective in improving the maximal velocity of contraction for a given absolute resistance . Mean velocity with loads of 0.37 , 6.6 , 16.6 , and 20 kg improved by 21.1 , 15.8 , 16.9 , and 19.5 % , respectively . No significant differences in the percent improvement at the four different loads were apparent , indicating that no significant velocity-specific adaptations were present . The bench-press training group , utilizing heavy loads in its training , was the only group with improved one repetition maximum . Overall , findings point to the development of coordination as the determining factor in early velocity-specific strength gains 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 PURPOSE To compare effects on strength in the early phase of resistance training with one or three sets and fast or slow speeds . METHODS A total of 115 healthy , untrained subjects were r and omized to a control group or one of four training groups : one set fast ( approximately 140 degrees.s(-1 ) ) , three sets fast , one set slow ( approximately 50 degrees.s(-1 ) ) , or three sets slow . All subjects attended training 3 x wk(-1 ) for 6 wk . Subjects in the training groups performed unilateral elbow flexion contractions with a target six- to eight-repetition maximum load . Control subjects sat at the training bench but did not train . One repetition maximum strength , arm circumference , and biceps skinfold thickness were measured before and after training . RESULTS One slow set increased strength by 25 % ( 95 % CI 13 - 36 % , P < 0.001 ) . Three sets of training produced greater increases in strength than one set ( difference = 23 % of initial strength , 95 % CI 12 - 34 % , P < 0.001 ) and fast training result ed in a greater increase in strength than slow training ( difference = 11 % , 95 % CI 0.2 - 23 % , P = 0.046 ) . The interaction between sets and speed was negative ( -15 % ) and of borderline significance ( P = 0.052 ) , suggesting there is a benefit of training with three sets or fast speeds , but there is not an additive benefit of training with both . CONCLUSIONS Three sets of exercise produce twice the strength increase of one set in the early phase of resistance training . Training fast produces greater strength increases than training slow ; however , there does not appear to be any additional benefit of training with both three sets and fast contractions We previously reported that low‐intensity [ 50 % of one repetition maximum ( 1RM ) ] resistance training with slow movement and tonic force generation ( LST ) causes muscle hypertrophy and strength gain in older participants . The aim of this study was to determine whether resistance training with slow movement and much more reduced intensity ( 30%1RM ) increases muscle size and strength in older adults . Eighteen participants ( 60–77 years ) were r and omly assigned to two groups . One group performed very low‐intensity ( 30 % 1RM ) knee extension exercise with continuous muscle contraction ( LST : 3‐s eccentric , 3‐s concentric , and 1‐s isometric actions with no rest between each repetition ) twice a week for 12 weeks . The other group underwent intermitted muscle contraction ( CON : 1‐s concentric and 1‐s eccentric actions with 1‐s rest between each repetition ) for the same time period . The 1RM , isometric and isokinetic strengths , and cross‐sectional image of the mid‐thigh obtained by magnetic resonance imaging were examined before and after the intervention . LST significantly increased the cross‐sectional area of the quadriceps muscle ( 5·0 % , P<0·001 ) and isometric and isokinetic knee extension strengths ( P<0·05 ) . CON failed to increase muscle size ( 1·1 % , P = 0·12 ) , but significantly improved its strength ( P<0·05 ) . These results indicate that even if the intensity is as low as 30 % 1RM , LST can increase muscle size and strength in healthy older adults . The large total contraction time may be related to muscle hypertrophy and strength gain . LST would be useful for preventing sarcopenia in older individuals BACKGROUND Age-related decline in muscle power may be an early indicator of balance deficits and fall risk , even in nonfrail adults . This study examined the dose-dependent effect of power training on balance performance in healthy older adults . METHODS One hundred twelve community-dwelling healthy older adults ( 69 + /- 6 years ) were r and omized to 8 - 12 weeks of power training at 20 % ( LOW ) , 50 % ( MED ) , or 80 % ( HIGH ) of maximal strength , or a nontraining control ( CON ) group . Participants trained twice weekly ( five exercises ; three sets of eight rapid concentric/slow eccentric repetitions ) using pneumatic resistance machines . Balance , muscle performance ( strength , power , endurance , contraction velocity ) , and body composition were measured . RESULTS Power training significantly improved balance performance ( p = .006 ) in participants who underwent power training compared to controls . Low intensity power training produced the greatest improvement in balance performance ( p = .048 ) . Average contraction velocity at low load ( 40 % one repetition maximum [ 1RM ] ) at baseline independently predicted improvement in balance following training ( r = -.29 , p = .004 ) . CONCLUSIONS Power training improves balance , particularly using a low load , high velocity regimen , in older adults with initial lower muscle power and slower contraction . Further studies are warranted to define the mechanisms underlying this adaptation , as well as the optimum power training intensity for a range of physiological and clinical outcomes in older adults with varying levels of health status and functional independence This study investigated the effect of a 10-week power training ( PT ) program versus traditional resistance training ( TRT ) on functional performance , and muscular power and strength in older men . Twenty inactive volunteers ( 60–76 years old ) were r and omly assigned to a PT group ( three 8–10 repetition sets performed as fast a possible at 60 % of 1-RM ) or a TRT group ( three 8–10 repetition sets with 2–3 s contractions at 60 % of 1-RM ) . Both groups exercised 2 days/week with the same work output . Outcomes were measured with the Rikli and Jones functional fitness test and a bench and leg press test of maximal power and strength ( 1-RM ) . Significant differences between and within groups were analyzed using a two-way analysis of variance ( ANOVA ) . At 10 weeks there was a significantly ( P < 0.05 ) greater improvement in measures of functional performance in the PT group . Arm curling improved by 50 versus 3 % and a 30 s chair-st and improved by 43 versus 6 % in the PT and TRT groups , respectively . There was also a significantly greater improvement in muscular power ( P < 0.05 ) in the PT group . The bench press improved by 37 versus 13 % , and the leg press by 31 and 8 % in the PT and TRT groups , respectively . There was no significant difference between groups in improved muscular strength . It appears that in older men there may be a significantly greater improvement in functional performance and muscular power with PT versus low velocity resistance training 1 . The adaptations of the ankle dorsiflexor muscles and the behaviour of single motor units in the tibialis anterior in response to 12 weeks of dynamic training were studied in five human subjects . In each training session ten series of ten fast dorsiflexions were performed 5 days a week , against a load of 30 - 40 % of the maximal muscle strength . 2 . Training led to an enhancement of maximal voluntary muscle contraction ( MVC ) and the speed of voluntary ballistic contraction . This last enhancement was mainly related to neural adaptations since the time course of the muscle twitch induced by electrical stimulation remained unaffected . 3 . The motor unit torque , recorded by the spike-triggered averaging method , increased without any change in its time to peak . The orderly motor unit recruitment ( size principle ) was preserved during slow ramp contraction after training but the units were activated earlier and had a greater maximal firing frequency during voluntary ballistic contractions . In addition , the high frequency firing rate observed at the onset of the contractions was maintained during the subsequent spikes after training . 4 . Dynamic training induced brief ( 2 - 5 ms ) motor unit interspike intervals , or ' doublets ' . These doublets appeared to be different from the closely spaced ( + /-10 ms ) discharges usually observed at the onset of the ballistic contractions . Motor units with different recruitment thresholds showed doublet discharges and the percentage of the sample of units firing doublets was increased by training from 5.2 to 32.7 % . The presence of these discharges was observed not only at the onset of the series of spikes but also later in the electromyographic ( EMG ) burst . 5 . It is likely that earlier motor unit activation , extra doublets and enhanced maximal firing rate contribute to the increase in the speed of voluntary muscle contraction after dynamic training The effects of 18 wk of intensive strength and endurance training on knee extensor , knee flexor , and lower leg muscle mass and composition were studied in 76- to 78-yr-old women . Muscle cross-sectional area ( CSA ) , lean tissue CSA , and relative proportion of fat were determined using computed tomography . The strength-trained women increased their total muscle lean tissue CSA of the thigh ( 1.5 % ; P = 0.035 ) , quadriceps CSA ( 4.5 % ; P = 0.021 ) , quadriceps lean tissue CSA ( 5.8 % , P = 0.009 ) , and mean Hounsfield unit of the lower leg muscles ( 11.2 % ; P = 0.035 ) compared with the changes that occurred in the control group during the experiment . The change in quadriceps lean tissue CSA because of the strength training was also significant compared with that in the endurance group . The relative proportion of fat within the quadriceps muscle decreased due to the strength training compared with the changes that occurred in the endurance group . The results show that intensive strength training can induce skeletal muscle hypertrophy in elderly women and thereby also reduce the relative amount of intramuscular fat , whereas the effects of endurance training are negligible We performed a r and omized exercise training study to assess the effects of traditional Nautilus-style ( TR ) or superslow ( SS ) strength training on muscular strength , body composition , aerobic capacity , and cardiovascular endurance . Subjects were 14 healthy , sedentary women , 19–45 years of age ( mean ± SD age , 32.7 ± 8.9 years ) , r and omized to either the SS or TR training protocol s and trained 3 times per week for 10 weeks . Measurements were taken both before and after training , which included a maximal incremental exercise test on a cycle ergometer , body composition , and 1 repetition maximum ( 1RM ) tests on 8 Nautilus machines . Both groups increased their strength significantly on all 8 exercises , whereas the TR group increased significantly more than the SS group on bench press ( 34 % vs. 11 % ) , torso arm ( anterior lateral pull-down ) ( 27 % vs. 12 % ) , leg press ( 33 % vs. 7 % ) , leg extension ( 56 % vs. 24 % ) , and leg curl ( 40 % vs. 15 % ) . Thus , the TR group 's improvement in total exercise weight lifted was significantly greater than that of the SS group after testing ( 39 % vs. 15 % ) . Exercise duration on the cycle ergometer and work rate significantly improved for both groups , but there was no group-by-training interaction . No significant differences were found for body composition or additional aerobic variables measured . Both strength training protocol s produced a significant improvement in strength during a 10-week training period , but the TR protocol produced better gains in the absence of changes in percentage of body fat , body mass index , lean body mass , and body weight . In addition , strength training alone did not improve Vo2max , yet short-term endurance increased Resistance training ( RT ) has shown the most promise in reducing/reversing effects of sarcopenia , although the optimum regime specific for older adults remains unclear . We hypothesized myofiber hypertrophy result ing from frequent ( 3 days/wk , 16 wk ) RT would be impaired in older ( O ; 60 - 75 yr ; 12 women , 13 men ) , sarcopenic adults compared with young ( Y ; 20 - 35 yr ; 11 women , 13 men ) due to slowed repair/regeneration processes . Myofiber-type distribution and cross-sectional area ( CSA ) were determined at 0 and 16 wk . Transcript and protein levels of myogenic regulatory factors ( MRFs ) were assessed as markers of regeneration at 0 and 24 h postexercise , and after 16 wk . Only Y increased type I CSA 18 % ( P < 0.001 ) . O showed smaller type IIa ( -16 % ) and type IIx ( -24 % ) myofibers before training ( P < 0.05 ) , with differences most notable in women . Both age groups increased type IIa ( O , 16 % ; Y , 25 % ) and mean type II ( O , 23 % ; Y , 32 % ) size ( P < 0.05 ) . Growth was generally most favorable in young men . Percent change scores on fiber size revealed an age x gender interaction for type I fibers ( P < 0.05 ) as growth among Y ( 25 % ) exceeded that of O ( 4 % ) men . Myogenin and myogenic differentiation factor D ( MyoD ) mRNAs increased ( P < 0.05 ) in Y and O , whereas myogenic factor (myf)-5 mRNA increased in Y only ( P < 0.05 ) . Myf-6 protein increased ( P < 0.05 ) in both Y and O. The results generally support our hypothesis as 3 days/wk training led to more robust hypertrophy in Y vs. O , particularly among men . However , this differential hypertrophy adaptation was not explained by age variation in MRF expression OBJECTIVES Peak power declines more precipitously than strength with advancing age and is a reliable measure of impairment and a strong predictor of functional performance . We tested the hypothesis that a high-velocity resistance-training program ( HI ) would increase muscle power more than a traditional low-velocity resistance-training program ( LO ) . DESIGN R and omized controlled trial . SETTING University-based human physiology laboratory . PARTICIPANTS Thirty women with self-reported dis-ability ( aged 73 + 1 , body mass index 30.1 + 1.1 kg/mn ) . INTERVENTION We conducted a r and omized trial comparing changes in skeletal muscle power and strength after 16 weeks of HI or LO . Training was performed three times per week , and subjects completed three sets ( 8 - 10 repetitions ) of leg press ( LP ) and knee extension ( KE ) exercises at 70 % of the one-repetition maximum ( IRM ) . MEASUREMENTS One-repetition maximum ( 1 RM ) and peak power for KE and LP . RESULTS LP and KE relative training force and total work were similar between groups ( P > .05 ) . However , HI generated significantly higher power during training sessions than LO for LP ( 3.7-fold greater , P < .001 ) and KE ( 2.1-fold greater , P < .001 ) . Although LP and KE 1RM muscle strength increased similarly in both groups asa result of the training ( P < .001 ) , LP peak power increased significantly more in HI than in LO ( 267 W vs 139 W , P < .001 ) . Furthermore , HI result ed in a significantly greater improvement in LP power at 40 % , 50 % , 60%,70 % , 80 % , and 90 % of the 1 RM than did LO ( P < .05 ) . CONCLUSIONS HI improved 1RM strength similarly and was more effective in improving peak power than was traditional LO in older women . Improvements in lower extremity peak power may exert a greater influence on age-associated reductions in physical functioning than other exercise interventions We aim ed to determine if the time that muscle is under loaded tension during low intensity resistance exercise affects the synthesis of specific muscle protein fractions or phosphorylation of anabolic signalling proteins . Eight men ( 24 ± 1 years ( sem ) , BMI = 26.5 ± 1.0 kg m(-2 ) ) performed three sets of unilateral knee extension exercise at 30 % of one-repetition maximum strength involving concentric and eccentric actions that were 6 s in duration to failure ( SLOW ) or a work-matched bout that consisted of concentric and eccentric actions that were 1 s in duration ( CTL ) . Participants ingested 20 g of whey protein immediately after exercise and again at 24 h recovery . Needle biopsies ( vastus lateralis ) were obtained while fasted at rest and after 6 , 24 and 30 h post-exercise in the fed-state following a primed , constant infusion of l-[ring-(13)C(6)]phenylalanine . Myofibrillar protein synthetic rate was higher in the SLOW condition versus CTL after 24 - 30 h recovery ( P < 0.001 ) and correlated to p70S6 K phosphorylation ( r = 0.42 , P = 0.02 ) . Exercise-induced rates of mitochondrial and sarcoplasmic protein synthesis were elevated by 114 % and 77 % , respectively , above rest at 0 - 6 h post-exercise only in the SLOW condition ( both P < 0.05 ) . Mitochondrial protein synthesis rates were elevated above rest during 24 - 30 h recovery in the SLOW ( 175 % ) and CTL ( 126 % ) conditions ( both P < 0.05 ) . Lastly , muscle PGC-1α expression was increased at 6 h post-exercise compared to rest with no difference between conditions ( main effect for time , P < 0.001 ) . These data show that greater muscle time under tension increased the acute amplitude of mitochondrial and sarcoplasmic protein synthesis and also result ed in a robust , but delayed stimulation of myofibrillar protein synthesis 24 - 30 h after resistance exercise This study aim ed to compare the effect on neuromuscular performance of 2 isoinertial resistance training programs that differed only in actual repetition velocity : maximal intended ( MaxV ) vs. half-maximal ( HalfV ) concentric velocity . 21 resistance-trained young men were r and omly assigned to a MaxV ( n=10 ) or HalfV ( n=11 ) group and trained for 6 weeks using the full squat exercise . A complementary study ( n=8 ) described the acute metabolic and mechanical response to the protocol s used . MaxV training result ed in a likely more beneficial effect than HalfV on squat performance : maximum strength ( ES : 0.94 vs. 0.54 ) , velocity developed against all ( ES : 1.76 vs. 0.88 ) , light ( ES : 1.76 vs. 0.75 ) and heavy ( ES : 2.03 vs. 1.64 ) loads common to pre- and post-tests , and CMJ height ( ES : 0.63 vs. 0.15 ) . The effect on 20-m sprint was unclear , however . Both groups attained the greatest improvements in squat performance at their training velocities . Movement velocity seemed to be of greater importance than time under tension for inducing strength adaptations . Slightly higher metabolic stress ( blood lactate and ammonia ) and CMJ height loss were found for MaxV vs. HalfV , while metabolite levels were low to moderate for both conditions . MaxV may provide a superior stimulus for inducing adaptations directed towards improving athletic performance |
2,274 | 29,296,018 | Receiving both EBRT and BT increased the risk of stricture formation . | Background We performed a systematic review and meta- analysis to determine the prevalence and predictors of urethral stricture development post radiation therapy ( RT ) for prostate cancer ( PCa ) . | The purpose of this study was to report the outcomes of high-dose-rate ( HDR ) brachytherapy and hypofractionated external beam radiotherapy ( EBRT ) combined with long-term and rogen deprivation therapy ( ADT ) for National Comprehensive Cancer Network ( NCCN ) criteria -defined high-risk ( HR ) and very high-risk ( VHR ) prostate cancer . Data from 178 HR ( n = 96 , 54 % ) and VHR ( n = 82 , 46 % ) prostate cancer patients who underwent 192Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed . The mean dose to 90 % of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy . After five fractions of HDR treatment , EBRT with 10 fractions of 3 Gy was administered . All patients initially underwent ≥6 months of neoadjuvant ADT , and adjuvant ADT was continued for 36 months after EBRT . The median follow-up was 61 months ( range , 25–94 months ) from the start of radiotherapy . The 5-year biochemical non- evidence of disease , freedom from clinical failure and overall survival rates were 90.6 % ( HR , 97.8 % ; VHR , 81.9 % ) , 95.2 % ( HR , 97.7 % ; VHR , 92.1 % ) , and 96.9 % ( HR , 100 % ; VHR , 93.3 % ) , respectively . The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3 % of patients and Grade 3 in 9.6 % . The highest late gastrointestinal toxicities were Grade 2 in 2.8 % of patients and Grade 3 in 0 % . Although the 5-year outcome of this tri-modality approach seems favorable , further follow-up is necessary to vali date clinical and survival advantages of this intensive approach compared with the st and ard EBRT approach PURPOSE A Phase I/II protocol was conducted to examine the toxicity and efficacy of the combination of intensity-modulated radiation therapy ( IMRT ) with a single-fraction high-dose-rate ( HDR ) brachytherapy implant . METHODS AND MATERIAL S From 2001 through 2006 , 26 consecutive patients were treated on the trial . The primary objective was to demonstrate a high rate of completion without experiencing a treatment-limiting toxicity . Eligibility was limited to patients with T stage ≤2b , prostate-specific antigen ( PSA ) ≤20 , and Gleason score ≤7 . Treatment began with a single HDR fraction of 6Gy to the entire prostate and 9Gy to the peripheral zone , followed by IMRT optimized to deliver in 28 fractions with a normalized total dose of 70Gy . Patients received 50.4Gy to the pelvic lymph node . The prostate dose ( IMRT and HDR ) result ed in an average biologic equivalent dose > 128Gy ( α/β=3 ) . Patients whose pretreatment PSA was ≥10ng/mL , Gleason score 7 , or stage ≥T2b received short-term and rogen ablation . RESULTS Median followup was 53 months ( 9 - 68 months ) . There were no biochemical failures by either the American Society of Therapeutic Radiology and Oncology or the Phoenix definitions . The median nadir PSA was 0.32ng/mL. All the 26 patients completed the treatment as prescribed . The rate of Grade 3 late genitourinary toxicity was 3.8 % consisting of a urethral stricture . There was no other Grade 3 or 4 genitourinary or gastrointestinal toxicities . CONCLUSIONS Single-fraction HDR-boosted IMRT is a safe effective method of dose escalation for localized prostate cancer PURPOSE We compared acute and late genitourinary ( GU ) and gastrointestinal ( GI ) toxicities in prostate cancer patients treated with three different high-dose radiation techniques . METHODS AND MATERIAL S A total of 1,903 patients with localized prostate cancer were treated with definitive RT at William Beaumont Hospital from 1992 to 2006 : 22 % with brachytherapy alone ( BT ) , 55 % with image-guided external beam ( EB-IGRT ) , and 23 % external beam with high-dose-rate brachytherapy boost ( EBRT+HDR ) . Median dose with BT was 120 Gy for LDR and 38 Gy for HDR ( 9.5 Gy × 4 ) . Median dose with EB-IGRT was 75.6 Gy ( PTV ) to prostate with or without seminal vesicles . For EBRT+HDR , the pelvis was treated to 46 Gy with an additional 19 Gy ( 9.5 Gy × 2 ) delivered via HDR . GI and GU toxicity was evaluated utilizing the NCI-CTC criteria ( v.3.0 ) . Median follow-up was 4.8 years . RESULTS The incidences of any acute ≥ Grade 2 GI or GU toxicities were 35 % , 49 % , and 55 % for BT , EB-IGRT , and EBRT+HDR ( p < 0.001 ) . Any late GU toxicities ≥ Grade 2 were present in 22 % , 21 % , and 28 % for BT , EB-IGRT , and EBRT+HDR ( p = 0.01 ) , respectively . Patients receiving EBRT+HDR had a higher incidence of urethral stricture and retention , whereas dysuria was most common in patients receiving BT . Any Grade ≥ 2 late GI toxicities were 2 % , 20 % , and 9 % for BT , EB-IGRT , and EBRT+HDR ( p < 0.001 ) . Differences were most pronounced for rectal bleeding , with 3-year rates of 0.9 % , 20 % , and 6 % ( p < 0.001 ) for BT , EB-IGRT , and EBRT+HDR respectively . CONCLUSIONS Each of the three modern high-dose radiation techniques for localized prostate cancer offers a different toxicity profile . These data can help patients and physicians to make informed decisions regarding radiotherapy for prostate and enocarcinoma PURPOSE To report the genitourinary ( GU ) and gastrointestinal ( GI ) morbidity and erectile dysfunction in a r and omized trial comparing 2 methods of dose escalation for high- and intermediate-risk prostate cancer . METHODS AND MATERIAL S ASCENDE-RT ( And rogen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy ) enrolled 398 men , median age 68 years , who were then r and omized to either a st and ard arm that included 12 months of and rogen deprivation therapy and pelvic irradiation to 46 Gy followed by a dose-escalated external beam radiation therapy ( DE-EBRT ) boost to 78 Gy , or an experimental arm that substituted a low-dose-rate prostate brachytherapy ( LDR-PB ) boost . At clinic visits , investigators recorded GU and GI morbidity and information on urinary continence , catheter use , and erectile function . Exclusion of 15 who received non protocol treatment and correction of 14 crossover events left 195 men who actually received a DE-EBRT boost and 188 , an LDR-PB boost . Median follow-up was 6.5 years . RESULTS The LDR-PB boost increased the risk of needing temporary catheterization and /or requiring incontinence pads . At 5 years the cumulative incidence of grade 3 GU events was 18.4 % for LDR-PB , versus 5.2 % for DE-EBRT ( P<.001 ) . Compared with the cumulative incidence , the 5-year prevalence of grade 3 GU morbidity was substantially lower for both arms ( 8.6 % vs 2.2 % , P=.058 ) . The 5-year cumulative incidence of grade 3 GI events was 8.1 % for LDR-PB , versus 3.2 % for DE-EBRT ( P=.124 ) . The 5-year prevalence of grade 3 GI toxicity was lower than the cumulative incidence for both arms ( 1.0 % vs 2.2 % , respectively ) . Among men reporting adequate baseline erections , 45 % of LDR-PB patients reported similar erectile function at 5 years , versus 37 % after DE-EBRT ( P=.30 ) . CONCLUSIONS The incidence of acute and late GU morbidity was higher after LDR-PB boost , and there was a nonsignificant trend for worse GI morbidity . No differences in the frequency of erectile dysfunction were observed |
2,275 | 27,446,869 | MR imaging provides a reliable alternative in detecting small bowel activity in patients with Crohn 's disease .
Its advantages include high diagnostic accuracy and no radiation exposure while its disadvantages include high cost and limited availability | Introduction .
Crohn 's disease is most commonly found in the terminal ileum and colonic region .
Magnetic resonance has become a useful modality for assessing small bowel activity .
In this study , we performed a systematic review and meta- analysis on the use of MR in detecting small bowel activity as well as extramural complications in Crohn 's patients . | PURPOSE To prospect ively compare oral contrast-enhanced T2-weighted half-Fourier rapid acquisition with relaxation enhancement ( RARE ) magnetic resonance ( MR ) imaging with T1-weighted gadolinium-enhanced fast low-angle shot ( FLASH ) MR and st and ard examinations in the evaluation of Crohn disease . MATERIAL S AND METHODS Institutional review board approval and informed consent were obtained . Fifty-nine patients with Crohn disease underwent MR imaging after oral administration of a superparamagnetic contrast agent ; RARE plain and fat-suppressed sequences and FLASH sequences were performed before and after intravenous injection of gadolinium chelate . References were endoscopic , small-bowel barium , computed tomographic , ultrasonographic , and clinical -biochemical scoring of disease activity . Two radiologists analyzed MR images for presence and extent of Crohn disease lesions , presence of strictures or other complications , and degree of local inflammation . MR findings were correlated with endoscopic , radiologic , and clinical data ( kappa statistic and Spearman rank correlation test ) . RESULTS T2-weighted MR was 95 % accurate , 98 % sensitive , and 78 % specific for detection of ileal lesions . Agreement between T1- and T2-weighted images ranged from 0.77 for ileal lesions to 1.00 for colic lesions . T2-weighted MR enabled detection of 26 of 29 severe strictures , 17 of 24 enteroenteric fistulas , and all adhesions and abscesses ; T1-weighted MR enabled detection of 20 of 29 severe strictures , 16 of 24 enteroenteric fistulas , and all adhesions and abscesses . Complications leading to surgery were found in 12 ( 20 % ) patients ; these were assessed correctly with either T1- or T2-weighted images . T2-weighted signal intensities of the wall and mesentery correlated with biologic activity ( P < .001 , r of 0.774 and 0.712 , respectively ) . Interobserver agreement was 0.642 - 1.00 for T2-weighted and 0.711 - 1.00 for T1-weighted images . CONCLUSION T2-weighted MR can depict Crohn disease lesions and help assess mural and transmural inflammation with the same accuracy as gadolinium-enhanced T1-weighted MR . Combination of gadolinium-enhanced T1- and T2-weighted sequences is useful in the assessment of Crohn disease Background : Studies comparing magnetic resonance enterography ( MRE ) and computerized tomography enterography ( CTE ) for Crohn 's disease ( CD ) are scarce . Methods : The aim of this study was to prospect ively compare the sensitivity , specificity , and accuracy of abdominal MRE and CTE to assess disease activity and complications ( fistulas , strictures ) in ileocolonic CD . A total of 44 patients ( 23 male ; 21 female ; mean age 44 ) with ileocolonic CD underwent both MR and CT in a short time interval ( mean 5 days ) . A 16‐slice CT with intravenous contrast and an MRI with oral and paramagnetic intravenous contrast were performed . Ileocolonoscopy was used as the reference st and ard . Sensitivity values of CT and MR for detection of extraenteric signs of disease were compared with the McNemar test , with results of imaging studies , surgery , and physical examination as reference st and ards . Results : No significant differences in sensitivity , specificity , and accuracy were observed between MRE and CTE regarding the following parameters at the patient level : localization of CD ( P = 1.0 ) , bowel wall thickening ( P = 1.0 ) , bowel wall enhancement ( P = 1.0 ) , enteroenteric fistulas ( P = 0.08 ) , detection of abdominal nodes ( P = 1.0 ) , and perivisceral fat enhancement ( P = 0.31 ) . MR was significantly superior compared to CT in detecting strictures ( P = 0.04 ) . Per segment analysis showed that MRE was significantly superior to CTE in detecting ileal wall enhancement ( P = 0.02 ) . Conclusions : MR and CT are equally accurate to assess disease activity and bowel damage in CD . MR may be superior to CT in detecting intestinal strictures and ileal wall enhancement . MR may represent an alternative technique to CT in assessing ileocolonic CD . ( Inflamm Bowel Dis 2010 PURPOSE To evaluate activity staging of Crohn 's disease ( CD ) measured with MR-enterography using ileoscopy as reference st and ard . MATERIAL S AND METHODS A prospect i ve study was made of 61 patients with CD . All patients underwent MR-enterography and ileoscopy . MRI activity was measured by means of an ad hoc developed score , as well as by analysis of the imaging findings , and was compared with the SES-CD score obtained via ileoscopy . Examinations were performed using a 1.0 T scanner . RESULTS MRI score discriminates between active and inactive disease with an area under the ROC curve of 0.941 . Overall correlation with the st and ard reference SES-CD score was moderate to strong ( Spearman 's r=0.62 p<0.001 ) . Agreement between both methods in staging patients with ileal CD as inactive , mild or moderate to severe was good ( Cohen 's κ=0.60 ) . Differences in means of the MRI activity scores of the three groups showed statistical significance ( p<0.01 ) . CONCLUSIONS The MRI score is a reliable predictor of activity in ileal CD and can stage patients in a way comparable to endoscopy . 1.0 T scans are valid for performing radiological evaluation of ileal Crohn 's disease BACKGROUND & AIMS Magnetic resonance ( MR ) enterography is a recommended imaging technique for detecting intestinal involvement in Crohn 's disease ( CD ) . However , the diagnostic accuracy of MR enterography has not been compared directly what that of enteroscopy of the jejunum and proximal ileum . We evaluated the usefulness of MR enterocolonography ( MREC ) by comparing its findings with those from balloon-assisted enteroscopy . METHODS In a prospect i ve study , MREC and enteroscopy were performed within 3 days of each other on 100 patients . Ulcerative lesions and all mucosal lesions were evaluated . Physicians and radiologists were blinded to results from other studies . Findings from MREC were compared directly with those from enteroscopy ; the sensitivity and specificity with which MREC detected CD lesions were assessed . RESULTS MREC detected ulcerative lesions and all mucosal lesions in the small intestine with 82.4 % sensitivity ( 95 % confidence interval [ CI ] , 75.4%-87.7 % ) and 67.5 % sensitivity ( 95 % CI , 63.1%-70.0 % ) ; specificity values were 87.6 % ( 95 % CI , 83.7%-90.6 % ) and 94.8 % ( 95 % CI , 90.1%-97.5 % ) . MREC detected major stenosis with 58.8 % sensitivity ( 95 % CI , 37.6%-77.2 % ) and 90.0 % specificity ( 95 % CI , 88.4%-91.5 % ) and all stenoses with 40.8 % sensitivity ( 95 % CI , 30.8%-49.4 % ) and 93.7 % specificity ( 95 % CI , 91.1%-95.9 % ) . CONCLUSIONS MREC is useful for detecting active lesions in the small intestine . However , MR imaging is less sensitive for detecting intestinal damage , such as stenoses . Enteroscopy is preferred for identifying intestinal damage . Suitable imaging approaches should be selected to assess CD lesions in deep small intestine In the European Cooperative Crohn 's Disease Study patients from 14 centers were included in whom diagnosis was made within 2 years before study entry on the basis of generally accepted radiological , endoscopical and /or histological criteria or a combination of all . Reasons for exclusion were : diagnosis older than 2 years in patients who did not require active treatment , age less than 18 years , duration of symptoms less than 3 months , presence of complications which potentially required emergency surgery . Data on clinical features were obtained in 633 patients , of whom 452 were eligible to participate in the study . In 110 patients r and omized to placebo the natural course of Crohn 's disease was studied . Patients with ileocolonic involvement were younger than patients with either colonic or small intestinal involvement only . Classic ileitis terminalis was present in 14 % of the patients . 49 % of the patients had combined involvement of both the small and large intestine . 30 % of patients had only small intestinal involvement , and in 21 % colonic disease was present . Small intestinal involvement was associated with a significantly lower Crohn 's Disease Activity Index ( CDAI ) than other anatomical locations of the disease . Perianal disease was more often associated with colonic than with small intestinal involvement . 60 % of placebo patients with active disease at entry achieved at least a transient remission within the initial 5 months of study . After 2 years , 23 % of patients with active disease at entry and 68 % of patients with quiescent disease had reached or maintained a remission , respectively . By stepwise multiple linear regression analysis long duration of disease between diagnosis and r and omization , normal serum albumin and combined involvement of small intestine and colon were identified as predictors of a more favorable outcome of patients treated with placebo . In contrast , extensive small bowel disease , treatment with steroids and bowel resection prior to study entry correlated with a less favorable outcome . However , by life table analysis outcome of previously untreated and treated patients in the placebo group was similar Objectives To prospect ively compare conventional MRI sequences , dynamic contrast enhanced ( DCE ) MRI and diffusion weighted imaging ( DWI ) with histopathology of surgical specimens in Crohn ’s disease . Methods 3-T MR enterography was performed in consecutive Crohn ’s disease patients scheduled for surgery within 4 weeks . One to four sections of interest per patient were chosen for analysis . Evaluated parameters included mural thickness , T1 ratio , T2 ratio ; on DCE-MRI maximum enhancement ( ME ) , initial slope of increase ( ISI ) , time-to-peak ( TTP ) ; and on DWI apparent diffusion coefficient ( ADC ) . These were compared with location-matched histopathological grading of inflammation ( AIS ) and fibrosis ( FS ) using Spearman correlation , Kruskal – Wallis and Chi-squared tests . Results Twenty patients ( mean age 38 years , 12 female ) were included and 50 sections ( 35 terminal ileum , 11 ascending colon , 2 transverse colon , 2 descending colon ) were matched to AIS and FS . Mural thickness , T1 ratio , T2 ratio , ME and ISI correlated significantly with AIS , with moderate correlation ( r = 0.634 , 0.392 , 0.485 , 0.509 , 0.525 , respectively ; all P < 0.05 ) . Mural thickness , T1 ratio , T2 ratio , ME , ISI and ADC correlated significantly with FS ( all P < 0.05 ) . Conclusions Quantitative parameters from conventional , DCE-MRI and DWI sequences correlate with histopathological scores of surgical specimens . DCE-MRI and DWI parameters provide additional information . Key points• Conventional MR enterography can be used to assess Crohn ’s disease activity.• Several MRI parameters correlate with inflammation and fibrosis scores from histopathology.• Dynamic contrast enhanced imaging and diffusion weighted imaging give additional information.• Quantitative MRI parameters can be used as biomarkers to evaluate Crohn ’s disease activity Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research , derived from extensive review of published literature . When data that will withst and objective scrutiny are not available , a recommendation may be made based on a consensus of experts . Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty . Guidelines are intended to be flexible , not necessarily indicating the only acceptable approach , and should be distinguished from st and ards of care that are inflexible and rarely violated . Given the wide range of choices in any health-care problem , the physician should select the course best suited to the individual patient and the clinical situation presented . These guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee . Expert opinion is solicited from the outset for the document . The quality of evidence upon which a specific recommendation is based is as follows : Grade A : Homogeneous evidence from multiple well- design ed r and omized ( therapeutic ) or cohort ( descriptive ) controlled trials , each involving a number of participants to be of sufficient statistical power . Grade B : Evidence from at least one large well- design ed clinical trial with or without r and omization , from cohort or case – control analytic studies , or well- design ed meta- analysis . Grade C : Evidence based on clinical experience , descriptive studies , or reports of expert committees . The Committee review s guidelines in depth , with participation from experienced clinicians and others in related fields . The final recommendations are based on the data available at the time of the production of the document and may be up date d with pertinent scientific developments at a later time Background : We developed novel magnetic resonance enterocolonography ( MREC ) for simultaneously evaluating both small and large bowel lesions in patients with Crohn 's disease ( CD ) . The aim of this study was to evaluate the diagnostic performance of MREC by comparing results of this procedure to those of endoscopies for evaluating the small and large bowel lesions of patients with CD . Methods : Thirty patients with established CD were prospect ively examined by newly developed MREC . Patients underwent ileocolonoscopy ( ICS ) ( 24 procedures ) or double‐balloon endoscopy ( DBE ) ( 10 procedures ) after MREC on the same day . Two gastroenterologists and two radiologists who were blinded to the results of another study evaluated endoscopy and MREC findings , respectively . Results : In colonic lesions the sensitivities of the MREC for deep mucosal lesions ( DML ) , all CD lesions , and stenosis were 88.2 , 61.8 , and 71.4 % , respectively , while the specificities were 98.1 , 95.3 , and 97.7 % , respectively . In small intestinal lesions , MREC sensitivities for DML , all CD lesions , and stenosis were 100 , 85.7 , and 100 % , respectively , while specificities were 100 , 90.5 , and 93.1 % , respectively . Endoscopic scores were significantly correlated with MREC scores . Eleven ( 46 % ) of the 24 patients who were clinical ly not suspected to show stricture were observed to demonstrate stricture by radiologists . Conclusions : Our results demonstrated that MREC can simultaneously detect the CD lesions of the small and large intestine . MREC can be performed without radiation exposure , the use of enema , or the placement of a naso‐jejunal catheter . MREC and endoscopy have comparable abilities for evaluating mucosal lesions of patients with CD . ( Inflamm Bowel Dis 2010 ; Background Crohn ’s disease ( CD ) is a lifelong , relapsing and remitting inflammatory condition of the intestine . Medical imaging is crucial for diagnosis , phenotyping , activity assessment and detecting complications . Diverse small bowel imaging tests are available but a st and ard algorithm for deployment is lacking . Many hospitals employ tests that impart ionising radiation , of particular concern to this young patient population . Magnetic resonance enterography ( MRE ) and small bowel ultrasound ( USS ) are attractive options , as they do not use ionising radiation . However , their comparative diagnostic accuracy has not been compared in large head to head trials . METRIC aims to compare the diagnostic efficacy , therapeutic impact and cost effectiveness of MRE and USS in newly diagnosed and relapsing CD . Methods METRIC ( IS RCT N03982913 ) is a multicentre , non-r and omised , single-arm , prospect i ve comparison study . Two patient cohorts will be recruited ; those newly diagnosed with CD , and those with suspected relapse . Both will undergo MRE and USS in addition to other imaging tests performed as part of clinical care . Strict blinding protocol s will be enforced for those interpreting MRE and USS . The Harvey Bradshaw index , C-reactive protein and faecal calprotectin will be collected at recruitment and 3 months , and patient experience will be assessed via question naires . A multidisciplinary consensus panel will assess all available clinical and imaging data up to 6 months after recruitment of each patient and will define the st and ard of reference for the presence , localisation and activity of disease against which the diagnostic accuracy of MRE and USS will be judged . Diagnostic impact of MRE and USS will be evaluated and cost effectiveness will be assessed . The primary outcome measure is the difference in per patient sensitivity between MRE and USS for the correct identification and localisation of small bowel CD . Discussion The trial is open at 5 centres with 46 patients recruited . We highlight the importance of stringent blinding protocol s in order to delineate the true diagnostic accuracy of both imaging tests and discuss the difficulties of diagnostic accuracy studies in the absence of a single st and ard of reference , describing our approach utilising a consensus panel whilst minimising incorporation bias . Trial registration METRIC - IS RCT N03982913 – 05.11.13 Background and Goals : Magnetic resonance ( MR ) enterography provides the advantages of conventional enteroclysis and those of cross-sectional imaging . Adequate luminal distension , combined with ultrafast sequences , results in excellent delineation of mural and extramural manifestations of Crohn ’s disease . Recent technical advances , including ultra – high-field strength MR with its capability to provide fast multiplanar images with excellent soft tissue contrast , are only rarely included in abdominal studies . Study : One hundred four consecutive patients with a proved or suspected diagnosis of ileitis terminalis were prospect ively selected for MR imaging studies and ileocolonoscopy . The final diagnosis was based on histopathological findings or based on a combined endpoint of clinical , laboratory , endoscopic , and imaging findings . Results : According to the endoscopic examination , stenosis was present in 26 patients ( 25 % ) and could be ruled out in 78 patients ( 75 % ) . Total agreement between MR and endoscopy could be reached in 74 patients ( 71 % ) . Histology indicated absence of inflammation in 50 patients ( 48 % ) . MR and endoscopic findings were concordant in 38 patients ( 76 % ) and 37 patients ( 74 % ) , respectively . Corresponding results by ileocolonoscopy were 37 true negative , 29 true positive , 4 false positive , and 12 false negative ( sensitivity , 70.7 % ; specificity , 74 % ) . Conclusions : MR enterography with a 3.0-T scanner is a powerful tool in the evaluation of ileal diseases , and has therefore made MR enterography the first-line modality at our institution in patients with suspected inflammatory bowel disease Background : Ileocolonoscopy represents the diagnostic st and ard in the work-up of patients with inflammatory bowel diseases ( IBD ) . Patients are often reluctant to be colonoscoped because of the invasiveness and pain sensation during colonoscopy . Aims : To compare the usefulness of transabdominal ultrasound ( US ) and magnetic resonance imaging ( MRI ) in assessing disease extension and activity in patients with IBD restricted to the terminal ileum and large bowel . Patients and Methods : 61 patients with IBD [ 37 Crohn 's disease ( CD ) and 24 ulcerative colitis ( UC ) ] were prospect ively studied . All patients underwent clinical and laboratory assessment , ileocolonoscopy , transabdominal sonography , and MRI within 5 days . Involved bowel segments were defined as those with bowel wall thickness > 3 mm and increased Doppler signal on US or contrast enhancement of the bowel wall on MRI . To compare disease activity endoscopic , MRI and US findings were grade d with newly developed scores . Results : The segment-by-segment analysis revealed an overall accuracy of 89 % for US and 73 % for MRI in identifying active IBD . The accuracy was better in patients with UC than in patients with CD for both US and MRI . The endoscopic activity index ( EAI ) correlated stronger with the US activity index ( r = 0.884 ) than with the MRI activity index ( r = 0.344 ) . The correlation of US and MRI activity indices with EAI was better in patients with UC compared with patients with CD . All three imaging methods showed a significant correlation with clinical disease activity in patients with UC but not in patients with CD . Conclusion : This study provides strong evidence that US should be considered as a first-choice method for follow-up of patients with IBD of the terminal ileum and large bowel Background : Magnetic resonance imaging ( MRI ) of the bowel is a valuable diagnostic tool for assessing disease activity in patients with inflammatory bowel disease ( IBD ) . We compared magnetic resonance enterography ( MRE ) with and without water enema to conventional ileocolonoscopy to evaluate the advantage of a water enema for MRI diagnostics of Crohn 's disease ( CD ) . Methods : We prospect ively evaluated 50 patients with known CD . MRE with enema was performed in 23 cases , whereas 27 patients received an MRE without enema . All patients underwent conventional ileocolonoscopy . We assessed the degree of inflammation in both modalities , evaluating up to seven bowel segments in each patient . We compared MRE with and without rectal enema to each other and to conventional ileocolonoscopy . Results : MRE achieved a sensitivity and specificity of 100 % and 74 % , respectively , for detection of inflammation in the terminal ileum with enema and a sensitivity and specificity of 72 % and 87 % , respectively , without enema . Considering the colon , MRE with enema had a sensitivity of 79 % ( specificity 96 % ) , while the examination without enema showed a sensitivity of 38 % ( specificity 99 % ) . MRE with enema proved statistically superior to MRE without enema in detecting inflammation in the terminal ileum , ascending colon , and rectum ( P < 0.05 ) . Conclusions : MRE with enema is a valuable diagnostic tool for assessing inflammation in CD patients . Water enema is well tolerated and significantly improves detection of inflammation in the terminal ileum . Water enema should therefore be included in MRE protocol s for CD patients . ( Inflamm Bowel Dis 2012 BACKGROUND & AIMS Capsule endoscopy ( CE ) detects small bowel Crohn 's disease with greater diagnostic yield than radiologic procedures , although there are concerns that CE has low specificity . We compared the sensitivity and specificity of CE , magnetic resonance imaging enterography ( MRE ) and computed tomography enterography ( CTE ) in patients with suspected or newly diagnosed Crohn 's disease . METHODS We performed a prospect i ve , blinded study of 93 patients scheduled to undergo ileocolonoscopy , MRE , and CTE and subsequently CE if stenosis was excluded . Physicians reporting CE , MRE , and CTE results were blinded to patient histories and findings from ileocolonoscopy and other small bowel examinations . Results were compared with those from ileoscopy ( n = 70 ) , ileoscopy and surgery ( n = 4 ) , or surgery ( n = 1 ) . RESULTS Twenty-one patients had Crohn 's disease in the terminal ileum . The sensitivity and specificity for diagnosis of Crohn 's disease of the terminal ileum were 100 % and 91 % by CE , 81 % and 86 % by MRE , and 76 % and 85 % by CTE , respectively . Proximal Crohn 's disease was detected in 18 patients by using CE , compared with 2 and 6 patients by using MRE or CTE , respectively ( P < .05 ) . Small bowel stenosis was observed in 5 patients by using CTE and 1 patient by using MRE . Cross-sectional imaging results indicated additional stenoses in only 2 of the patients who received complete ileocolonoscopies . CONCLUSIONS In suspected or newly diagnosed Crohn 's disease , MRE and CTE have comparable sensitivities and specificities . In patients without endoscopic or clinical suspicion of stenosis , CE should be the first line modality for detection of small bowel Crohn 's disease beyond the reach of the colonoscope Background : The diagnosis of small bowel Crohn ’s disease ( CD ) is performed by ileocolonoscopy , whereas the assessment of its extension can be achieved by radiologic studies or , noninvasively , by magnetic resonance ( MR ) enterography and bowel sonography ( BS ) . However , few comparative studies exist directly comparing the diagnostic accuracy of BS and MRI . The aim of this study was to evaluate the diagnostic accuracy of BS and MRI for the diagnosis of small bowel CD . Methods : We prospect ively performed a noninferiority diagnostic study including 234 consecutive subjects with suspected small bowel CD . All patients underwent IC ( used as gold st and ard for diagnosis ) , BS , and MR enterography performed in r and om order by physicians who were blinded about the results . Results : The diagnosis of small bowel CD was made in 120 of 249 subjects ( 48 % ) . Sensitivity , specificity , positive predictive value , and negative predictive value for CD diagnosis were 94 % , 97 % , 97 % , and 94 % for BS and 96 % , 94 % , 94 % , and 96 % for MR enterography , respectively . BS was less accurate than MR enterography in defining CD extension ( r = 0.69 ) , whereas the concordance in terms of CD location between the 2 procedures was high ( k = 0.81 ) . Also , MRI showed a fair concordance with BS about strictures ( k = 0.82 ) and abscesses ( k = 0.88 ) , with better detection of enteroenteric fistulas ( k = 0.67 ) . Conclusions : BS and MR enterography are 2 accurate procedures for the diagnosis of small bowel CD , although MR seems to be more sensitive in defining its extension . BS could be used to select the patients for subsequent MRI examination OBJECTIVE The objective of our study was to prospect ively obtain pilot data on the accuracy of MR enterography for detecting small-bowel Crohn 's disease compared with CT enterography and with a clinical reference st and ard based on imaging , clinical information , and ileocolonoscopy . SUBJECTS AND METHODS The study group for this blinded prospect i ve study was composed of 33 patients with suspected active Crohn 's ileal inflammation who were scheduled for clinical CT enterography and ileocolonoscopy and had consented to also undergo MR enterography . The MR enterography and CT enterography examinations were each interpreted by two radiologists with disagreements resolved by consensus . The reports from ileocolonoscopy with or without mucosal biopsy were interpreted by a gastroenterologist . The reference st and ard for the presence of small-bowel Crohn 's disease was based on the final clinical diagnosis by the referring gastroenterologist after review ing all of the available information . RESULTS All 33 patients underwent CT enterography and ileocolonoscopy , 30 of whom also underwent MR enterography . The sensitivities of MR enterography and CT enterography for detecting active small-bowel Crohn 's disease were similar ( 90.5 % vs 95.2 % , respectively ; p = 0.32 ) . The image quality scores for MR enterography examinations were significantly lower than those for CT enterography ( p = 0.005 ) . MR enterography and CT enterography identified eight cases ( 24 % ) with a final diagnosis of active small-bowel inflammation in which the ileal mucosa appeared normal at ileocolonoscopy . Furthermore , enterography provided the only available imaging in three additional patients who did not have ileal intubation . CONCLUSION MR enterography and CT enterography have similar sensitivities for detecting active small-bowel inflammation , but image quality across the study cohort was better with CT . Cross-sectional enterography provides complementary information to ileocolonoscopy Background : High diagnostic accuracy is reported for magnetic resonance enterography ( MRE ) in Crohn ’s disease ( CD ) , but few studies have evaluated its role in abdominal fistulae . The primary aim of this study was to assess the reliability of MRE in the identification of internal fistulae in CD . Methods : One hundred and eighty-six patients with moderate CD ( CD Activity Index : 250–400 ) were prospect ively selected from the inflammatory bowel disease clinic of Parma University Hospital . Eligible patients had already undergone nutritional screening , pancolonoscopy , and computed tomography enterography ( CTE ) in the month before enrollment . MRE was performed according to the study protocol . Additional fluoroscopic contrast-enhanced studies or surgical evaluation were used for discordance between CTE and MRE results . A consensus committee resolved equivocal findings . Surgical findings and /or fluoroscopic contrast-enhanced studies together with the clinical data were considered the composite “ reference st and ard ” to which the results of MRE were compared . Results : MRE identified 22 internal fistulae in 21 patients ( 11 % ) , of whom 4 ( 19 % ) also had perianal fistulae and found 7 abscesses ( 33 % ) . Forty-one ( 22 % ) additional patients with perianal fistulae were identified . Thirteen patients ( 57 % ) with internal fistulae required enteral nutrition support . No statistically significant differences were found between MRE and CTE in fistula detection . There was also no significant difference between MRE and the composite diagnosis in those who underwent surgery ( n = 8) and /or contrast-enhanced studies ( n = 7 ) . Conclusions : CTE and MRE accurately detect internal fistulae in CD . MRE is preferable because it avoids radiation . Reliable identification of internal fistulae by MRE should permit earlier and improved treatment Background : Differentiation between inflammatory and fibromatous strictures in Crohn 's disease ( CD ) is difficult but crucial for therapeutic decisions . The aim of this study was to assess the best noninvasive imaging method for the detection and differentiation of inflammatory and fibromatous stenoses in CD in comparison to endoscopic and histologic evaluation . Methods : Patients with suspected CD strictures were included . According to a formalized endoscopic and histologic protocol , strictures were classified as inflammatory , mixed , and fibrostenotic . Strictures were further analyzed using fluorine 18‐labeled fluoro‐2‐deoxy‐D‐glucose ( 18FDG ) / positron emission tomography ( PET ) low‐dose computed tomography ( CT ) , magnetic resonance ( MR ) enteroclysis and transabdominal ultrasound using st and ardized scoring systems . Results : Thirty patients with 37 strictures were evaluated ( inflamed n = 22 ; mixed n = 12 , fibromatous n = 3 ) . 18FDG‐PET/CT detected 81 % , MR‐enteroclysis 81 % , and ultrasound 68 % of the strictures . Correct differentiation rates of strictures were 57 % for MRE , 53 % for 18FDG‐PET/CT , and 40 % for ultrasound . Differences of detection rates and differentiation rates were not statistically significant . When combining transabdominal ultrasound with 18FDG‐PET/CT or MR‐enteroclysis all strictures that required invasive treatment were detected . Conclusions : Detection rates of the strictures were not significantly different between 18FDG‐PET/CT , MR‐enteroclysis , and ultrasound . Despite good stricture detection rates relating to our gold st and ard , 18FDG‐PET/CT nor MR‐enteroclysis nor ultrasound can accurately differentiate inflamed from fibrotic strictures . A combination of MR‐enteroclysis and ultrasound as well as a combination of 18FDG‐PET/CT and ultrasound result ed in a 100 % detection rate of strictures requiring surgery or endoscopic dilation therapy , suggesting the combination of these methods as an alternative to endoscopy at least in the group of patients not able to perform an adequate bowel preparation . ( Inflamm Bowel Dis 2012 ; Abstract Objective . In patients , with symptomatic Crohn 's disease ( CD ) , valid information about the presence or absence of small bowel disease activity and stenosis is clinical ly important . Such information supports decisions about medical or surgical therapy and can be obtained with MR enterography ( MRE ) or CT enterography ( CTE ) . Material s and methods . A total of 50 patients with symptomatic pre-existing CD and a dem and for small bowel imaging to support changes in treatment strategy were included in this prospect i ve and blinded study . MRE and CTE were performed on the same day in alternating order and subsequently compared with the gold st and ard : pre-defined lesions at ileoscopy ( n = 30 ) or surgery with ( n = 12 ) or without ( n = 3 ) intra-operative enteroscopy . Results . A total of 35 patients had active small bowel CD ( jejunum 0 , ileum 1 , (neo)-terminal ileum 34 ) and 20 had small bowel stenosis . The sensitivity and specificity of MRE for detection of small bowel CD was 74 % and 80 % compared to 83 % and 70 % with CTE ( p ≥ 0.5 ) . MRE and CTE detected small bowel stenosis with 55 % and 70 % sensitivities , respectively ( p = 0.3 ) and 92 % specificities . Conclusions . MRE and CTE have comparable diagnostic accuracies for detection of small bowel CD and stenosis . In symptomatic patients with CD and high disease prevalence , positive predictive values are favorable but negative predictive values are low . Consequently , MRE and CTE can be relied upon , if a positive result is obtained whereas a negative enterography should be interpreted with caution PURPOSE To prospect ively compare the accuracy of computed tomographic ( CT ) and magnetic resonance ( MR ) enterography and small-bowel follow-through ( SBFT ) examination for detection of active small-bowel inflammation and extraenteric complications in patients with Crohn disease ( CD ) . MATERIAL S AND METHODS The institutional review board approved the study protocol ; informed consent was obtained from all participants . Thirty-one consecutive patients who had CD or who were suspected of having CD underwent CT and MR enterography , SBFT , and ileocolonoscopy . Two independent readers review ed CT and MR enterographic and SBFT images for presence of active terminal ileitis and extraenteric complications . Accuracy values of CT and MR enterography and SBFT for identification of active terminal ileitis were evaluated with the receiver operating characteristic method , with ileocolonoscopic findings as the reference st and ard . Sensitivity values of CT and MR enterography and SBFT for detection of extraenteric complications were compared by using the McNemar test , with results of imaging studies , surgery , and physical examination as reference st and ards . RESULTS The study population included 30 patients ( 17 men , 13 women ; mean age , 29.0 years ) with CD . Differences in areas under the receiver operating characteristic curves for CT enterography ( 0.900 and 0.894 ) , MR enterography ( 0.933 and 0.950 ) , and SBFT ( 0.883 and 0.928 ) for readers 1 and 2 , respectively , in the detection of active terminal ileitis were not significant ( P > .017 ) . Sensitivity values for detection of extraenteric complications were significantly higher for CT and MR enterography ( 100 % for both ) than they were for SBFT ( 32 % for reader 1 and 37 % for reader 2 ) ( P < .001 ) . CONCLUSION Because MR enterography has a diagnostic effectiveness comparable to that of CT enterography , this technique has potential to be used as a radiation-free alternative for evaluation of patients with CD OBJECTIVE The purpose of this study was to evaluate the sensitivity and specificity of MR imaging in assessing the activity of Crohn 's disease . SUBJECTS AND METHODS Thirty symptomatic patients with Crohn 's disease but uncertain disease activity were prospect ively examined using MR imaging . Twenty-nine patients were scored using the Crohn 's disease activity index . Six hundred milliliters of water orally and 1 mg of glucagon intramuscularly were given before imaging . Breath-hold images were obtained using T2-weighted turbo spin-echo , T1-weighted fast low-angle shot , and fat-suppressed gadolinium-enhanced T1-weighted fast low-angle shot sequences . Images were assessed by two radiologists who were unaware of the patient 's symptoms , clinical scoring , and other imaging tests , and who reached a consensus about the imaging findings ( bowel wall thickening , bowel wall enhancement , and perienteric changes ) and determined the absence or presence of active disease in each patient . MR imaging findings were correlated with endoscopy and surgery . RESULTS Twenty-three patients had active disease and seven patients had inactive disease . One hundred twenty-four of a total of 168 bowel segments were examined with both MR imaging and endoscopy or surgery . On a per patient basis , MR imaging had an overall sensitivity of 91 % and a specificity of 71 % for active disease . The Crohn 's disease activity index had a sensitivity of 92 % and a specificity of 28 % . On a per segment basis , MR imaging had a sensitivity of 59 % and a specificity of 93 % . Bowel wall thickening of greater than 4 mm , bowel wall enhancement ( ratio of signal intensity of abnormal to normal bowel > 1.3:1 ) , and increased mesenteric vascularity were useful in identifying active disease . A layered enhancement pattern after the IV administration of gadolinium was highly specific for active inflammation . CONCLUSION MR imaging is useful in assessing the activity of Crohn 's disease and may be helpful when clinical scoring is equivocal Crohn 's disease is a lifelong disease arising from an interaction between genetic and environmental factors , but observed predominantly in developed countries of the world . The precise aetiology is unknown and therefore a causal therapy is not yet available . Within Europe there is a distinct North – South gradient , but the incidence appears to have increased in Southern countries in recent years.1 Many patients live with a considerable symptom burden despite medical treatment in the hope that the aetiology of the disease will shortly be revealed and curative therapies emerge . Since it is uncertain that the precise pathogenesis of Crohn 's disease will be revealed anytime soon , clinicians have to advise patients on the basis of information available today rather than an unknown future . Despite a multiplicity of r and omised trials there will always be many questions that can only be answered by the exercise of judgement and opinion . This leads to differences in practice between clinicians , which may be brought into sharp relief by differences in emphasis between countries . The Consensus endeavours to address these differences . The Consensus is not meant to supersede the guidelines of different countries ( such as those from the UK,2 Germany,3 or France ) , which reach broadly the same conclusions since they are , after all , based on the same evidence . Rather , the aim of the Consensus is to promote a European perspective on the management of Crohn 's disease and its dilemmas . Since the development of guidelines is an expensive and time-consuming process , it may help to avoid duplication of effort in the future . A Consensus is also considered important because an increasing number of therapeutic trials are based in Europe , especially in eastern European countries where practice guidelines have yet to be published . This document is based on the European consensus on the diagnosis and management of Crohn 's |
2,276 | 16,034,908 | Disease severity after supplementary high-dose vitamin A was significantly worse in children who received vitamin A compared with placebo .
The evidence did not suggest a significant reduction with vitamin A adjunctive treatment in mortality , measures of morbidity , nor an effect on the clinical course of pneumonia in children with non-measles pneumonia . | BACKGROUND Acute respiratory infections , mostly in the form of pneumonia , are the leading causes of death in children under five years of age in developing countries .
Some clinical trials have demonstrated that vitamin A supplementation reduces the severity of respiratory infection and mortality in children with measles .
OBJECTIVES To determine whether adjunctive vitamin A is effective in infants and children diagnosed with non-measles pneumonia . | Abstract Objective : To evaluate the effect of simultaneous zinc and vitamin A supplementation on diarrhoea and acute lower respiratory infections in children . Study design : R and omised double blind placebo controlled trial . Setting : Urban slums of Dhaka , Bangladesh . Participants and methods : 800 children aged 12 - 35 months were r and omly assigned to one of four intervention groups : 20 mg zinc once daily for 14 days ; 200 000 IU vitamin A , single dose on day 14 ; both zinc and vitamin A ; placebo . The children were followed up once a week for six months , and morbidity information was collected . Results : The incidence and prevalence of diarrhoea were lower in the zinc and vitamin A groups than in the placebo group . Zinc and vitamin A interaction had a rate ratio ( 95 % confidence interval ) of 0.79 ( 0.66 to 0.94 ) for the prevalence of persistent diarrhoea and 0.80 ( 0.67 to 0.95 ) for dysentery . Incidence ( 1.62 ; 1.16 to 2.25 ) and prevalence ( 2.07 ; 1.76 to 2.44 ) of acute lower respiratory infection were significantly higher in the zinc group than in the placebo group . The interaction term had rate ratios of 0.75 ( 0.46 to 1.20 ) for incidence and 0.58 ( 0.46 to 0.73 ) for prevalence of acute lower respiratory infection . Conclusions : Combined zinc and vitamin A synergistically reduced the prevalence of persistent diarrhoea and dysentery . Zinc was associated with a significant increase in acute lower respiratory infection , but this adverse effect was reduced by the interaction between zinc and vitamin A. What is already known on this topic Trials of vitamin A supplementation have failed to show a beneficial effect on morbidity in children Experimental studies have shown that , in the presence of zinc deficiency , vitamin A supplementation fails to reverse vitamin A deficiency Coexistence of deficiencies of zinc and vitamin A could be a reason for the failure of vitamin A supplementation , but data in humans are limited What this paper adds Combined zinc and vitamin A supplementation is more effective in reducing persistent diarrhoea and dysentery than either vitamin A or zinc alone Zinc alone increased respiratory illnesses , but interaction between zinc and vitamin A reduced this adverse There is uncertainty over whether vitamin A supplementation reduces morbidity among children with sub clinical deficiency of the vitamin . Hence a double-blind , placebo-controlled trial of the effect of vitamin A supplementation on childhood morbidity was conducted among 11,124 children aged 6 - 83 months in the northwest of Haiti . After a r and om start , children were sequentially assigned by household units to receive either megadose vitamin A or placebo in three distribution cycles 4 months apart . 2 to 8 weeks after each administration of the vitamin A and placebo capsules , indicators of childhood morbidity were reassessed through interviews conducted in the homes of participating families . The vitamin A group was found to have an increased 2-week prevalence of all symptoms and signs of childhood morbidity assessed , including diarrhoea ( rate ratio [ RR ] = 1.09 , 95 % confidence interval 1.05 - 1.14 ) , rhinitis ( RR = 1.02 , 95 % confidence interval 1.00 - 1.04 ) , cold/flu symptoms ( RR = 1.04 , 95 % confidence interval 1.01 - 1.06 ) , cough ( RR = 1.07 , 95 % confidence interval 1.03 - 1.11 ) , and rapid breathing ( RR = 1.18 , 95 % confidence interval 1.09 - 1.27 ) . The study shows an increased 2-week prevalence of diarrhoea and the symptoms of respiratory infections after vitamin A supplementation OBJECTIVES --To determine whether a single high dose of vitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme . DESIGN --Opportunistic controlled trial . SETTING --Jumla district , Nepal . SUBJECTS -- All children aged under 5 years ; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation . MAIN OUTCOME MEASURES --Mortality and cause of death in the five months after supplementation . RESULTS --Risk of death for children aged 1 - 59 months in supplemented communities was 26 % lower ( relative risk 0.74 , 95 % confidence interval 0.55 to 0.99 ) than in unsupplemented communities . The reduction in mortality was greatest among children aged 6 - 11 months : death rate ( deaths/1000 child years at risk ) was 133.8 in supplemented children and 260.8 in unsupplemented children ( relative risk 0.51 , 0.30 to 0.89 ) . The death rate from diarrhoea was also reduced ( 63.5 supplemented v 97.5 unsupplemented ; relative risk 0.65 , 0.44 to 0.95 ) . The extra cost per death averted was about $ 11 . CONCLUSION --The results support a role for Vitamin A in increasing child survival . The supplementation programme was readily integrated with the ongoing community health programme at little extra cost BACKGROUND R and omized controlled trials have shown inconsistent responses of childhood pneumonia to the use of vitamin A as an adjunct to the st and ard treatment of pneumonia . OBJECTIVE We evaluated the effect of a moderate dose of vitamin A as an adjunct to st and ard antimicrobial treatment on the duration of respiratory signs in children with pneumonia . DESIGN Children , aged 2 - 59 mo , with pneumonia and weight-for-age < 50th percentile who had been admitted to the Baca Ortíz Children 's Hospital in Quito , Ecuador , were r and omly assigned to receive 50,000 IU ( aged 2 - 12 mo ) or 100,000 IU ( aged > 12 - 59 mo ) vitamin A or a placebo . RESULTS Of the 287 children enrolled , 145 received vitamin A and 142 received placebo . No overall differences were observed between the 2 groups in the duration of signs of pneumonia . Multiple linear regression showed a significant interaction between basal serum retinol concentration and vitamin A group for the time ( in h ) to remission of respiratory signs ( beta = -3.57 , SE = 1.09 , P = 0.001 ) . Duration of clinical signs was less in children with basal serum retinol concentrations > 200 microg/L who received vitamin A supplements than in children with similar concentrations who received placebo ( 69.9 + /- 49.9 h compared with 131.3 + /- 143.9 h ; P = 0.049 ) . CONCLUSIONS Overall , we found no effect of a moderate dose of vitamin A supplementation on the duration of uncomplicated pneumonia in underweight or normal-weight children aged < 5 y. However , a beneficial effect was seen in children with high basal serum retinol concentrations Because the clinics in a multiclinic r and omized clinical trial represent neither fixed stratification effects nor r and om classificatory effects , the appropriate analysis of data from such a trial has been the subject of controversy and debate . The following are some of the elements of controversy that are discussed and for which some bases for resolution are proposed . Is it ever valid to ignore the effects of clinics in the analysis ? Is it ever valid to drop clinics from the analysis ? Is a multiclinic clinical trial similar in structure or not to a single-clinic clinical trial in which patients have been stratified on a classificatory factor ? Assuming that clinics will be taken account of in the analysis , should it be the weighted or the unweighted average of within-clinic treatment differences that is to be taken as the best estimate of the overall difference between the treatments ? How should the data be analyzed if there is evidence of treatment-by-clinic interaction Vitamin A supplementation of population s of vitamin A-deficient preschool-age children has been shown to reduce childhood mortality , but the primary preventive effects of such supplements on childhood infectious diseases have not been carefully evaluated . We conducted an individually r and omized , placebo-controlled , double-masked trial among 1,407 Indonesian preschool-age children , to measure the effects of high dose vitamin A on acute respiratory and diarrheal illnesses . Signs and symptoms of morbidity were monitored using every other day home surveillance by trained interviewers . High dose vitamin A supplements increased the incidence of acute respiratory illnesses ( ARI ) by 8 % , and acute lower respiratory illnesses ( ALRI ) by 39 % . These detrimental effects on acute lower respiratory illnesses were most marked in children with adequate nutritional status ( rate ratio 1.83 , 95 % confidence interval 1.257 - 2.669 ) . In contrast , vitamin A tended to be protective of ALRI in chronically malnourished children ( rate ratio 0.71 , 95 % confidence interval 0.375 - 1.331 ) . There was no overall effect of high-dose vitamin A supplements on the incidence of diarrheal disease ( rate ratio 1.06 , 95 % confidence interval 0.920 - 1.225 ) . However , we found a significant interaction between supplementation and age : vitamin A increased the incidence of diarrhea in children < 30 mo of age , but tended to reduce the incidence in older children . The finding of a significant adverse effect of vitamin A supplements in adequately nourished children highlights the need to review the criteria for selecting population s of preschool-age children for vitamin A supplementation BACKGROUND The relative-dose-response ( RDR ) test is used to identify subjects with marginal liver vitamin A stores , but its use has not been evaluated during episodes of infection . OBJECTIVE The objective was to assess , with the RDR test , the vitamin A status of children recovering from pneumonia . DESIGN As part of a double-blind , placebo-controlled clinical trial of high-dose vitamin A supplements among children hospitalized with pneumonia in Lima , Peru , we examined the association of treatment group , nutritional status , severity of disease , and induction of the acute phase response [ on the basis of serum C-reactive protein ( CRP ) ] on serum retinol and the RDR test . RESULTS Serum retinol was low at admission and increased significantly in both the vitamin A and placebo groups during recovery . Serum CRP had a significant , inverse association with retinol at both admission and discharge . Serum retinol and CRP concentrations never differed significantly between the treatment groups . Among subjects with CRP > or = 10 mg/L , 21 % in the vitamin A group and 20 % in the placebo groups ( P = 0.83 ) had a positive RDR test result . Among subjects with CRP < 10 mg/L , 56 % in the placebo group but only 6 % in the vitamin A group had positive RDR test results ( P = 0.002 ) . CONCLUSION The RDR test was useful in assessing the vitamin A status of children recovering from pneumonia when CRP concentrations were < 10 mg/L but not when CRP concentrations were higher Vitamin A deficiency and acute lower respiratory tract infections coexist as important public health problems in many developing countries . We carried out a r and omized , double-blind , placebo-controlled trial to examine whether large doses of vitamin A given to Tanzanian children who are admitted to the hospital with nonmeasles pneumonia would reduce the severity of respiratory disease . Six hundred eighty-seven children were r and omly assigned to receive either placebo or vitamin A [ 200 000 IU ( 60 mg retinol equivalents ) for children > 1 y of age and 100000 IU ( 30 mg retinol equivalents ) for infants ] on the day of admission and another dose on the following day . Of the 346 children in the vitamin A group , 13 died in the hospital , compared with 8 of 341 children in the placebo group ; the relative mortality was 1.63 ( 95 % CI : 0.67 , 3.97 ; P = 0.28 ) . The mean number of days of hospitalization was the same in both groups ( 4.2 d ) . There were no differences between the vitamin A and placebo groups in the duration of hospital stay when examined within categories of children stratified by age , sex , breast-feeding status , nutritional status at baseline , or quartile of dietary vitamin A intake in the 4 mo before admission to the hospital . There were also no differences in the mean number of days of fever , rapid respiratory rate , or hypoxia , whether these endpoints were examined in the total number of subjects or in a subset with more severe clinical conditions at baseline . Large doses of vitamin A had no protective effect on the course of pneumonia in hospitalized Tanzanian children The effect of high-dose vitamin A supplementation on recovery from morbidity and on recovery from nosocomial morbidity of hospitalized children has been poorly studied and results are conflicting . The effect of daily , low doses has never been assessed . We investigated the effect of a single high dose and daily , low doses of vitamin A on diarrhea , acute lower respiratory tract infections ( ALRIs ) , and all-cause fevers in 900 hospitalized preschool-age children in the Democratic Republic of Congo in a r and omized , double-blind , placebo-controlled clinical trial . The high-dose treatment group received 200,000 IU vitamin A ( 100,000 IU if aged < 12 mo ) orally on the day of admission , the low-dose treatment group received 5000 IU vitamin A/d until discharge . Data on all-cause morbidity were collected daily . Mortality rates were not significantly different among the 3 groups . High-dose vitamin A supplementation had no significant effect on the duration of moderate or severe diarrhea nor on the duration and incidence of ALRIs and all-cause fevers . Children in the high-dose group with no edema had an increased risk of severe nosocomial diarrhea ( relative risk : 2.42 ; 95 % CI : 1.15 , 5.11 ) . Low-dose vitamin A supplementation significantly reduced the incidence of severe diarrhea in severely malnourished children ( relative risk : 0.21 ; 95 % CI : 0.07 , 0.62 ) but showed no significant effect on the duration of moderate or severe diarrhea or on the duration and incidence of ALRIs and all-cause fevers . Supplementation with high doses of vitamin A did not reduce morbidity in this population of malnourished and sub clinical ly vitamin A-deficient children ; daily , low doses appeared more beneficial for severely malnourished children Nasopharyngeal colonization is a risk factor for pneumococcal disease , a leading cause of complications and death in infants . We assessed the impact of vitamin A supplementation in reducing pneumococcal colonization in infants from an area with endemic vitamin A deficiency . We recruited 464 2-mo-old infants from a rural area in South India . Infants were r and omly assigned to receive two 7000-microg retinol equivalent doses of vitamin A ( n = 239 ) or placebo ( n = 225 ) orally at birth , and nasopharyngeal specimens were collected at ages 2 , 4 and 6 mo . We studied the effect of vitamin A on culture-confirmed pneumococcal colonization and on the distribution of pneumococcal serotypes . Analyses were conducted by intention-to-treat . The risk of colonization among infants aged 4 mo who were not colonized by age 2 mo was significantly reduced in the vitamin A group compared with the placebo group [ odds ratio 0.51 ( 0.28 , 0.92 ) , P = 0.02 ) . The odds of colonization were 27 % lower in the treatment group than in the placebo group [ odds ratio 0.73 ( 0.48 , 1.1 ) , P = 0.13 ] . No differences were detected in the prevalence of invasive serotypes . The risk of colonization with penicillin-resistant isolates was 74 % lower in the vitamin A group than in the placebo group at 2 mo of age . However , the prevalence of penicillin-resistant isolates was only 4 % . Neonatal vitamin A supplementation may play a role in lowering morbidity rates associated with pneumococcal disease by delaying the age at which colonization occurs Incidence , duration , and severity of diarrhea and respiratory symptoms were monitored weekly for 1 y in 15,419 children 6 - 60 mo of age in a r and omized , placebo-controlled , masked clinical trial conducted in southern India . Half the children received weekly doses of 8.7 mumol ( 2500 microgram ) vitamin A and 46 mumol ( 20 mg ) vitamin E ( treated ) and the other half , 46 mumol vitamin E ( control ) . Medical and ocular examinations and anthropometric measurements were obtained before and after 52 wk of intervention . Ocular examinations also were obtained after 26 wk . Supplements were delivered weekly from calibrated dispenser bottles by community health volunteers who also recorded each mother 's recall of daily morbidity of her child during the previous week . Baseline characteristics of treated and control subjects were similar and documented a prevalence of 11 % xerophthalmia and 72 % undernutrition . Weekly treatment with the low-dose vitamin A supplement did not influence the incidence , severity , or duration of diarrhea or respiratory infections and did not influence linear or ponderal growth The relationship of vitamin A deficiency and child survival has been documented in a number of studies but not in others , yet the relationship of vitamin A with child morbidity remains controversial . We prospect ively examined the relationship of dietary vitamin A intake and the incidences of diarrhea and respiratory infection among 28,753 Sudanese children between the ages of 6 mo and 6 y. Total dietary vitamin A intake was strongly and inversely associated with the risk of diarrhea ( multivariate risk in top relative to bottom quintile = 0.58 , 95 % confidence interval = 0.47 - 0.72 ) ; we also observed a strong inverse association with the risk of having cough and fever ( 0.60 , 0.45 - 0.81 ) . On the other h and , we noted a significantly positive association of dietary vitamin A intake and incidence of cough alone ( 1.69 , 1.52 - 1.88 ) , a sign that may be assocsated with a healthy respiratory epithelium . Vitamin A intake was also negatively associated with the risk of measles . These prospect i ve data emphasize the importance of adequate dietary vitamin A intake to protect the health of children in developing countries BACKGROUND The efficacy of micronutrient supplementation in improving childhood health and survival in developing countries may be specific to the micronutrient used and health outcome measured . OBJECTIVE We evaluated the effect of vitamin A and zinc supplementation on overall rates of childhood diarrheal disease and respiratory tract infections and rates stratified by household and personal characteristics . DESIGN A double-blind , r and omized , placebo-controlled trial was carried out in which 736 children aged 6 - 15 mo living in a periurban area of Mexico City were assigned to receive vitamin A every 2 mo , zinc daily , vitamin A and zinc together , or placebo . Children were followed for 12 mo to determine overall counts of diarrheal episodes and respiratory tract infections . RESULTS Vitamin A supplementation was associated with a 27 % increase in diarrheal disease [ risk ratio ( RR ) : 1.27 ; 95 % CI : 1.10 , 1.45 ; P < 0.001 ] and a 23 % increase in cough with fever ( RR : 1.23 ; 95 % CI : 1.02 , 1.47 ; P = 0.02 ) , whereas zinc had no effect on these outcomes . Vitamin A supplementation decreased diarrhea in children from households with dirt floors but increased diarrhea in children from households with nondirt floors , piped water , and indoor bathrooms . Zinc supplementation decreased diarrhea in children from households with dirt floors and whose mothers were more educated . Vitamin A supplementation increased cough with fever in children from less-crowded households that lacked indoor bathrooms and in children of less-educated mothers . CONCLUSIONS Vitamin A increases diarrheal disease and respiratory tract infections in young children in periurban areas of Mexico City . Vitamin A and zinc have more heterogeneous effects in different subgroups of children Objectives : To evaluate the effect of vitamin A supplementation 24 h after delivery on breastmilk retinol concentration . Methods : Fifty low income women were r and omly assigned to a single oral dose of 209 μmol of Vitamin A or none at delivery . Maternal serum and breastmilk retinol levels and infant morbidity and anthropometry were serially assessed . Results : Mean ( 95 % CI ) serum retinol levels increased in the supplemented mothers at 2.77 ( 2.3 , 3.2 ) compared to 1.15 ( 0.9 , 1.4 ) μmol/l in controls ( P<0.05 ) and remained at a significantly higher level of 1.59 ( 1.4 , 1.8 ) μmul/l compared to 1.33 ( 1.8 , 1.5 ) μmol/l in the control group ( P<0.001 ) up to a period of three months . Breastmilk retinol concentration was also greater at 24 h after supplementation , mean ( CI ) 11.34 ( 9.0 , 13.7 ) μmol/l , compared to 2.95 ( 2.3 , 3.6 ) μmol/l in the control group ( P<0.0001 ) , and remained higher for the next six months at 1.06 ( 0.9 , , 1.3 ) μmol/l compared to 0.73 ( 0.6 , 0.8 ) μmol/l in the control group ( P<0.02 ) . Infants of the supplemented mothers had reduced mean duration of respiratory tract infection of 3.1 ( 2.7 , 3.5 ) days compared to 3.7 ( 3.3 , 4.2 ) days ( P<0.03 ) and mean incidence of febrile illness 0.1 ( 0.1 , 0.1 ) compared to control infants 0.3 ( 0.3 , 0.3 ) days , ( P<0.002 ) . Conclusion : Vitamin A supplementation of malnourished mothers maintains higher breastmilk retinol concentration for at least six months and reduces the duration of respiratory tract infection and febrile illness in their breastfed infants . Sponsorship : The study was supported by the International Centre for Diarrhoeal Disease Research and the United States Agency for International Development OBJECTIVE To test the hypothesis that high-dose vitamin A supplements will enhance recovery of children hospitalized for the treatment of community-acquired pneumonia . DESIGN We conducted a r and omized , double-blind , placebo-controlled clinical trial of high-dose vitamin A supplements among children 3 months to 10 years of age ( N = 95 ) admitted to hospital with community-acquired pneumonia in Lima , Peru . Children < /=1 year of age received 100 000 IU of water-miscible vitamin A on admission to the hospital and an additional 50 000 IU the next day . Children > 1 year of age received 200 000 IU on admission and 100 000 IU the next day . RESULTS Children receiving vitamin A ( n = 48 ) had lower blood oxygen saturation ( the mean difference on day 3 in hospital was 1.1 % ) , higher prevalence rates of retractions ( 37 % in the vitamin A group vs 15 % in the placebo group on day 3 ) , auscultatory evidence of consolidation ( 28 % in the vitamin A group vs 17 % in the placebo group on day 3 ) , and were more likely to require supplemental oxygen ( 21 % in the vitamin A group vs 8 % in the placebo group on day 3 ) than children in the placebo group ( n = 47 ) . Adjustment for baseline severity of disease and nutritional status did not alter the association of vitamin A with increased clinical severity , although the difference in blood oxygen saturation was no longer statistically significant . No differences were seen in duration of hospitalization or in chest x-ray changes 14 days after admission . No deaths occurred , and toxicity of vitamin A was not seen . CONCLUSIONS This study indicates that high-dose vitamin A supplements cause modest adverse effects in children recovering from pneumonia and should not be used therapeutically in such patients unless there is clinical evidence of vitamin A deficiency or concurrent measles infection BACKGROUND Studies on the effect of vitamin A supplementation on growth have yielded various results . It is possible that such growth is dependent on the burden of infectious diseases in the population . METHODS We analysed data from a r and omized , double-masked , placebo-controled trial to examine the role of respiratory infections and diarrhoea in modifying the growth response to vitamin A supplementation . A single high dose of vitamin A or placebo was given every 4 months to 1405 children aged 6 - 48 months , and 4430 child treatment cycles were used in this analysis . RESULTS Vitamin A supplementation modestly improved linear but not ponderal growth of children who experienced little respiratory infection and especially of those who had vitamin A intake below the normative requirement ( < 400 RE/day ) . Children who received vitamin A and were free of respiratory infection grew 0.22 cm/4 months ( 95 % CI : 0.08 , 0.37 ) more in height than the placebo group , but those with > or = 21.5 % of days of respiratory infection did not show a significant growth response to vitamin A supplementation . Children who experienced no respiratory infection and had vitamin A intake < 400 RE/day benefited most , gaining 0.31 cm/4 months ( 95 % CI : 0.10 , 0.52 ) more in height compared to the placebo group . Diarrhoea was associated with poorer growth , but did not significantly modify the effect of vitamin A supplementation on growth . CONCLUSIONS Vitamin A supplementation improves the linear growth of children who have a low intake of vitamin A but this impact is muted with increasing levels of respiratory infections BACKGROUND Low-birth-weight ( LBW ) infants ( < 2,500 g ) are at increased risk of respiratory infection in the first few months of life and have low liver stores of vitamin A. As retinol is essential for respiratory epithelial cell differentiation , deficiency could result in pathological changes in the respiratory epithelium , with respiratory problems . OBJECTIVE A r and omised , double-blind , placebo-controlled trial to investigate the effect of vitamin A supplementation on the incidence and severity of respiratory infections in LBW infants during their first year of life . METHOD One hundred and thirty LBW infants ( gestational age < 36 weeks and birth weight 950 - 1,700 g ) were enrolled in the study . The infants were r and omly allocated to a vitamin A or placebo group . Infants in the vitamin A group received 25,000 IU of vitamin A ( retinyl palmitate , Arovit drops , Roche , Basle , Switzerl and ) on study days 1 , 4 and 8 . Study day 1 was between 36 and 60 hours after delivery . Infants in the placebo group received a placebo ( formulated by Roche ) with a similar appearance and packed in the same dropper bottles as the vitamin A drops . RESULTS Vitamin A supplementation markedly improved serum retinol levels . After the last vitamin A dose , the vitamin A group had higher mean serum retinol concentrations than the placebo group ( 45.77 + /- 17.07 micrograms/dl v. 12.88 + /- 6.48 micrograms/dl , P = 0.0001 ) . There was no evidence of improvement in neonatal or post-neonatal respiratory problems associated with vitamin A supplementation . Vitamin A and placebo groups did not differ in the occurrence or duration of respiratory distress or the need for head-box oxygen . There were also no significant differences in the cumulative probability of developing lower or upper respiratory tract infection through the first year of life . There was a slight suggestion of an increase in the risk of hospitalisation with pneumonia associated with vitamin A supplementation . The cumulative probability of being hospitalised with pneumonia by 6 months of age was 24.6 % ( 7 hospitalisations ) in the vitamin A group compared with 7.4 % ( 2 hospitalisations ) in the placebo group ( log rank test P = 0.04 ) . After adjusting for risk factors this difference was no longer significant . CONCLUSION Vitamin A supplementation in LBW neonates may not reduce incidence or severity of respiratory infections . These results do not negate the importance of improving vitamin A status in children as an important public health measure to reduce morbidity and mortality from other childhood infections The present study was carried out to investigate risk factors for sub clinical vitamin A deficiency in children under 6 years of age in the urban slums of Nagpur , India . The study included 308 nonxerophthalmic children selected r and omly from the study population . On the basis of conjunctival impression cytology the prevalence of sub clinical vitamin A deficiency was estimated to be 35.7 per cent . The current study recognised a significant association between female gender , illiterate mother , lower socioeconomic status , more than two children under 5 years of age at home , undernutrition , history of diarrhoea , measles , acute respiratory infections , and sub clinical vitamin A deficiency on univariate analysis . Logistic regression analysis identified significance of female gender , more than two children under 5 years of age at home , undernutrition , and measles in the outcome of sub clinical vitamin A deficiency . Estimates of attributable risk proportions and population attributable risk proportions for significant and preventable risk factors confirmed their etiological and preventable role in sub clinical vitamin A deficiency respectively OBJECTIVE To determine the benefit of oral vitamin A supplementation for acute respiratory syncytial virus ( RSV ) infection . DESIGN An observational study of vitamin A and retinol binding protein ( RBP ) levels in RSV-infected in patients and two control groups ; and a r and omized , controlled trial of vitamin A supplementation for RSV-infected in patients . SETTING Two tertiary care , urban teaching hospitals . PARTICIPANTS Thirty-two RSV-infected in patients ( aged 2 to 58 months ) , 35 hospitalized children without respiratory infections ( aged 2 to 19 months ) , and 39 healthy outpatient controls ( aged 2 to 67 months ) . INTERVENTION The RSV-infected group was r and omized to receive a single dose of 100,000 IU oral vitamin A or placebo . MAIN OUTCOME MEASURES Serum vitamin A and RBP levels of all participants and clinical indicators of severity such as days of hospitalization , oxygen use , intensive care , intubation , and a daily severity score . RESULTS Mean vitamin a and RBP levels were lower in RSV-infected children than in healthy controls ( P > .05 ) . Among RSV-infected children , those admitted to the intensive care unit had lower mean vitamin A ( P = .03 ) and RBP levels ( P = .04 ) than those not in intensive care . Among children hospitalized without respiratory infection , those admitted to the intensive care unit had lower mean vitamin A levels ( P = .02 ) than those not in intensive care . In the RSV-infected children , no significant difference was seen between the vitamin A group ( n = 21 ) and the placebo group ( n = 11 ) in improvement in severity score , mean days of hospitalization , intensive care , or receipt of supplemental oxygen . CONCLUSIONS Serum vitamin A and RBP levels were low in children hospitalized with RSV infection and were lower in children admitted to the intensive care unit . Hospitalized control patients in intensive care also had lower levels than those treated on the ward . We observed no benefit from oral vitamin A supplementation for children hospitalized with RSV infection The associations of hemoglobin , hematocrit , and packed cell volume with socioeconomic factors , malaria , human immunodeficiency virus ( HIV ) infection , and nutritional status were examined among 687 children admitted to hospital with pneumonia participating in a double blind , placebo-controlled trial of vitamin A supplementation . Children were r and omized to receive 2 doses of vitamin A ( 200,000 IU ) or placebo at baseline , and additional doses at 4 and 8 months after discharge from hospital . Hemoglobin levels were measured at enrollment and , on a subset of 161 children , during follow-up . At baseline , hemoglobin concentration was positively associated with the number of possessions in the household , maternal level of education and quality of water supply , and inversely related to malaria infection after controlling for potential confounding variables . Children infected with HIV experienced a significant fall in mean hemoglobin levels over time . The risk of developing severe anemia ( < 7 g/dL ) during follow-up was lower for children who were breastfed for longer than 18 months as compared to those with less than 6 months of breastfeeding ( adjusted prevalence ratio = 0.14 , 95 % confidence interval [ CI ] = 0.02 , 0.93 ; P = 0.04 ) , and higher for children over two years of age as compared to 6 to 11 months-old infants ( adjusted prevalence ratio = 8.11 , 95 % CI = 1.2 , 55.8 ; P = 0.03 ) . Children with repeated diagnoses of malaria had 4.1 times the risk of developing severe anemia than did children without the diagnosis ( 95 % CI = 1.3 , 13.5 ; P = 0.02 ) . Vitamin A supplements were associated with an overall nonsignificant reduction of 14 % in the risk of developing severe anemia ( adjusted prevalence ratio = 0.86 , 95 % CI = 0.37 , 1.99 ; P = 0.73 ) . We conclude that malaria , HIV infection , low socioeconomic status , and short duration of breastfeeding are strong and independent determinants of adverse hematologic profiles in this population Background and objective : In developing countries low maternal vitamin A stores combined with increased dem and s of pregnancy and lactation may lead to its deficiency in breastfed infants . This study evaluates the effects of maternal supplementation with a high dose of vitamin A on the serum retinol levels of exclusively breastfed infants , and their morbidity in the first six months of life . Setting : Hospital based . Study design : R and omised controlled trial . Subjects and methods : Mothers of the test group ( n=150 ) were orally supplemented with a single dose of retinol ( 209 μmol ) soon after delivery and were advised exclusive breastfeeding for six months . Before supplementation retinol levels were estimated in the mothers ’ and newborns ’ blood , and in colostrum . On follow up , breastmilk and infants ’ serum retinol contents were assessed monthly for six months . Retinol level < 0.7 μmol/l indicated vitamin A deficiency . Morbidity patterns like vitamin A deficiency , diarrhoea , febrile illnesses , acute respiratory infection , measles , and ear infection were also studied and compared between the two groups . Results : Presupplement mean maternal serum retinol levels were 0.98 and 0.92 μmol/l and mean breastmilk levels were 3.85 and 3.92 μmol/l in the test and control groups respectively ( p>0.05 ) . Mean cord blood retinol levels were also comparable ( 0.68 v 0.64 μmol/l ) . After supplementation , the test group showed a rise in mean breastmilk retinol content ( 12.08 v 2.96 μmol/l ) which remained significantly higher for four months . The infants ’ mean serum retinol level , initially 322.06 % of the baseline value , was significantly higher for five months . In the control group , significant numbers of mothers and infants showed deficient breastmilk and serum retinol throughout the follow up ( p<0.01 ) . Decreased incidence and duration of various diseases were also found in the test group suggesting lesser morbidity . Conclusion : Maternal supplementation with single megadose vitamin A is an effective strategy for vitamin A prophylaxis of exclusively breastfed infants of 0–6 months Clinical and laboratory data to define conditions of apparent health , localised infection or inapparent infection were available for 74 anaemic Guatemalan preschool children in the baseline phase of a clinical trial of the effect of iron and vitamin A on haematological status to be correlated with serum levels of four circulating micronutrients -- iron , zinc , copper and retinol -- known to be influenced by activation of the acute-phase reaction . Upon enrolment , only 29.7 % of the children were free of all evidence of infection , 36.5 % had one or more localised conditions detected on clinical examination , and 33.8 % had an elevated white cell count and /or sedimentation rate , without localising features . These were classified as ' inapparent infections ' . With respect to the healthy children , levels of iron , zinc , and retinol declined and copper generally increased in the four categories of clinical infections ( acute respiratory infection , dermal infections , conjunctivitis , and ' other ' ) but were also displaced in inapparent infections . Some activation of the acute-phase response in anaemic children may occur in the absence of clinical findings . Care must be taken in interpreting circulating micronutrient levels in relation to nutritional status in such population OBJECTIVE To determine the effect of vitamin A supplementation on the risk of diarrhea and of acute respiratory infection . DESIGN Double-blind , r and omized , placebo-controlled trial . SETTING Dar-es-Salaam , Tanzania . SUBJECTS Six hundred eighty-seven children , 6 to 60 months old , hospitalized with pneumonia , who received vitamin A or placebo at baseline and at 4 and 8 months after discharge from hospital . MAIN OUTCOME VARIABLES Incidence and duration of episodes of diarrhea and respiratory tract infections during the year after discharge from the hospital . RESULTS Relative to those receiving placebo , children receiving vitamin A had a significantly smaller risk of severe watery diarrhea ( multivariate odds ratio = 0.56 , 95 % CI = 0.32 - 0.99 , P = .04 ) but a higher risk of cough and rapid respiratory rate ( multivariate odds ratio = 1.67 , 95 % CI = 1.17 - 2.36 , P = .004 ) . Vitamin A supplementation was also associated with increased risk of acute diarrhea among normally nourished children or children with stunted growth but was relatively protective among children with wasting disease ( P value for interaction = .01 ) . The apparently increased risk of respiratory tract infection was limited to children who were seronegative for human immunodeficiency virus ( HIV ) ( P value for interaction = .07 ) . CONCLUSIONS Vitamin A supplements provide a low-cost intervention against morbidity in HIV-infected and undernourished children . Supplements may also have serious non-lethal adverse outcomes in well-nourished individuals . Whether these apparent detrimental effects of vitamin A are transient or long-term needs to be examined A beneficial effect of periodic vitamin A supplementation on childhood mortality has been demonstrated , but the effect on morbidity is less clear . We investigated the effect of vitamin A supplementation on diarrhoea and acute lower-respiratory-tract infections ( ALRI ) in children from northeastern Brazil in a r and omised , double-blind , placebo-controlled community trial . 1240 children aged 6 - 48 months were assigned vitamin A or placebo every 4 months for 1 year . They were followed up at home three times a week , and data about the occurrence and severity of diarrhoea and ALRI were collected . Any child with cough and respiratory rate above 40 breaths per min was visited by a paediatrician . The overall incidence of diarrhoea episodes was significantly lower in the vitamin-A-supplemented group than in the placebo group ( 18.42 vs 19.58 x 10(-3 ) child-days ; rate ratio 0.94 [ 95 % Cl 0.90 - 0.98 ] ) . The benefit of supplementation was greater as regards severe episodes of diarrhoea ; the incidence was 20 % lower in the vitamin A group than in the placebo group ( rate ratio 0.80 [ 0.65 - 0.98 ] ) . With the st and ard definition of diarrhoea ( > or = 3 liquid or semi-liquid stools in 24 h ) the effect of vitamin A on mean daily prevalence did not reach significance , but as the definition of diarrhoea was made more stringent ( increasing number of stools per day ) , a significant benefit became apparent , reaching for diarrhoea with 6 or more liquid or semi-liquid stools in 24 h a 23 % lower prevalence . We found no effect of vitamin A supplementation on the incidence of ALRI . The reduction in severity of diarrhoea may be the most important factor in the lowering of mortality by vitamin A supplementation To determine the effect of a massive single oral dose of Vitamin A ( 200,000 IU ) supplementation on diarrhoea and acute respiratory infection ( ARI ) , a double blind placebo controlled trial involving 174 children under six years of age ( excluding infants ) was carried out in a Calcutta slum community . Ninety-one children received vitamin A supplementation ( experimental group ) and 83 children received a placebo ( control group ) . All the children were followed up for six months by active fortnightly surveillance for occurrence of diarrhoea or ARI and their duration . There was no statistically significant difference in the incidence of diarrhoeal episodes or ARI . However , there was a significant difference ( p<0.05 ) in the average duration of diarrhoea per episode ( 2.1 vs. 3 days ) between the experimental and control groups . Possible beneficial effects of a single oral dose of vitamin A supplementation on the incidence of diarrhoea and ARI could not be demonstrated in the present study Background . Previous studies of large-dose vitamin A supplementation on respiratory morbidity have produced conflicting results in a variety of population s. The influence of malnutrition has not been examined in the majority of these trials . We hypothesized that weekly low-dose vitamin A supplementation would prevent respiratory and diarrheal disease morbidity and that malnutrition might influence the efficacy of vitamin A supplementation . Methods . In a r and omized , double-blind , placebo-controlled field trial of 400 children , 6 to 36 months of age in a high And ean urban slum , half of the children received 10 000 IU of vitamin A weekly and half received placebo for 40 weeks . Children were visited weekly at home by physicians and assessed for acute diarrheal disease and acute respiratory infections . Results . Acute diarrheal disease and acute respiratory infection did not differ globally or by severity between supplement-treated and placebo groups . However , the incidence of acute lower respiratory infection ( ALRI ) was significantly lower in underweight ( weight-for-age z score [ WAZ ] < −2 SD ) supplement-treated children than in underweight children on placebo ( 8.5 vs 22.3 per 103 child-weeks ; rate ratio : 0.38 [ 95 % CI : 0.17–0.85 ] ) . ALRI incidence was significantly higher in normal-weight ( WAZ > −2 SD ) supplement-treated children than in normal-weight children on placebo ( 9.8 vs 4.4 per 103 child-weeks ; rate ratio : 2.21 [ 95 % CI : 1.24–3.93 ] ) . By logistic regression analysis the risk of ALRI was lower in underweight supplement-treated children than in underweight children on placebo ( point estimate 0.148 [ 95 % CI : 0.034–0.634 ] ) . In contrast , risk of ALRI was higher in normal-weight supplement-treated children ( WAZ > −1 SD to mean ) than in normal-weight children on placebo in the same WAZ stratum ( point estimate : 2.51 [ 95 % CI : 1.24–5.05 ] ) . The risk of severe diarrhea was lower in supplement-treated children 18 to 23 months of age than in children on placebo in this age group ( point estimate : 0.26 [ 95 % CI : 0.06–1.00 ] ) . Conclusions . Weekly low-dose ( 10 000 IU ) vitamin A supplementation in a region of sub clinical deficiency protected underweight children from ALRI and paradoxically increased ALRI in normal children with body weight over −1 SD . Protection from severe diarrhea was consistent with previous trials . Additional research is warranted to delineate potential beneficial and detrimental interactions between nutritional status and vitamin A supplementation regarding ALRI A nested case-control study of vitamin A deficiency and wasting as risk factors for mortality from AIDS and infections was done within a large prospect i ve cohort of human immunodeficiency virus (HIV)-infected injection drug users ( IDUs ) . Fifty adult subjects who died from AIDS and infections were matched with 235 controls who survived . Plasma vitamin A , weight , and body mass index were measured . Mean length of follow-up was 2.4 + /- 1.1 years . Vitamin A deficiency occurred in 50 % and wasting occurred in 38 % of patients in the last visit before death . CD4 cells count < 200/microL , wasting , and vitamin A deficiency were associated with mortality . There was a higher risk of death in HIV-infected subjects with vitamin A deficiency ( odds ratio [ OR ] , 4.6 ; 95 % confidence interval [ CI ] , 1.8 - 11.3 ) and wasting ( OR , 8.8 ; 95 % CI , 2.7 - 28.2 ) . Vitamin A deficiency and wasting are common during HIV infection and are independent predictors of mortality in HIV-infected IDUs OBJECTIVE To assess vitamin A status in children with pneumonia . INTERVENTIONS Thirty-four hospitalised patients with pneumonia were r and omly allocated into two groups : the study group , besides the routine treatment , received a high dose of aqueous retinyl palmitate oral solution ; the control group received only the routine treatment . METHODS The concentrations of plasma vitamin A and carotenoids were determined by colorimetric method . Retinol binding protein ( RBP ) was determined by the radial immunodiffusion technique . RESULTS After 1 week of treatment there was a statistically significant ( P < 0.05 ) increase in the levels ( mean + /- s.e . ) of vitamin A ( study group : 14.1 + /- 1.6 to 26.5 + /- 5.8 micrograms/dl ; control group : 16.1 + /- 3.3 to 24.1 + /- 2.3 micrograms/dl ) and RBP ( study group : 0.8 + /- 0.2 to 2.2 + /- 0.6 mg/dl ; control group : 0.6 + /- 0.2 to 3.0 + /- 0.5 mg/dl ) in both groups as compared to the baseline . On day 7 of treatment when the average levels of vitamin A ( 26.5 + /- 5.8 and 24.1 + /- 2.3 micrograms/dl ) were compared , there was no statistically significant difference between the groups . CONCLUSION This study suggests that low levels of circulating plasma vitamin A in child with pneumonia may be a consequence of acute phase of infectious disease OBJECTIVE A r and omized , double-blind , placebo-controlled intervention study was carried out in order to investigate whether consumption of a dietary supplement containing probiotic bacteria plus vitamins and minerals over a period of at least three months in winter/spring affects the duration , frequency , and severity of symptoms of naturally acquired common cold infections as well as cellular immune parameters . METHODS 477 healthy men and women ( aged 36 + /- 13 , mean + /- SD ) who had not been vaccinated against influenza were r and omly assigned to a group who received daily the probiotic multivitamin and mineral supplement ( verum ) or a placebo , for three ( n = 239 ) or for 5.5 months ( n = 238 ) . Cellular immune response was determined in 60 participants per study group by flow cytometry before and after 14 days of supplementation . RESULTS The incidence of respiratory tract infections regarded as being virally induced was 13.6 % lower in the verum group compared to the placebo group ( p = 0.07 ) . During respiratory tract infection episodes , the subjects recorded common cold and influenza-like symptoms daily . All symptoms were reduced in the verum group . We found a relative reduction of 19 % in the total symptom score ( p = 0.12 ) , 25 % in influenza symptoms ( p = 0.09 ) , and 54 % in the number of days with fever ( p = 0.03 ) . The duration of these infections was not affected . Leukocytes , lymphocytes , in particular T-lymphocytes including CD4 + and CD8 + cells , as well as monocytes were significantly higher increased in the verum group , during the first 14 days of supplementation compared to placebo . CONCLUSION These data indicate that the intake of a dietary supplement containing probiotic bacteria plus vitamins and minerals during a period of at least three months in winter/spring may reduce the incidence and the severity of symptoms in common cold infections in otherwise healthy adults . This may be due to stimulated cellular immunity Community trials of the efficacy of vitamin A supplementation in reducing preschool childhood mortality have produced conflicting results . To resolve the question , a r and omised , double-masked , placebo-controlled community trial of 28,630 children aged 6 - 72 months was carried out in rural Nepal , an area representative of the Gangetic flood plain of South Asia . R and omisation was carried out by administrative ward ; the vitamin-A-supplemented children received 60,000 retinol equivalents every 4 months and placebo-treated children received identical capsules containing 300 retinol equivalents . After 12 months , the relative risk of death in the vitamin-A-supplemented compared with the control group was 0.70 ( 95 % confidence interval 0.56 - 0.88 ) , equivalent to a 30 % reduction in mortality . The trial , which had been planned to last 2 years , was discontinued . The reduction in mortality was present in both sexes ( relative risk for boys 0.77 ; for girls 0.65 ) , at all ages ( range of relative risks 0.83 - 0.50 ) , and throughout the year ( 0.76 - 0.67 ) . The reduction in mortality risk was not affected by acute nutritional status , as measured by arm circumference . Thus , periodic vitamin A delivery in the community can greatly reduce child mortality in developing countries We carried out a r and omized , placebo‐controlled , double‐blinded trial to evaluate the effect on morbidity of high dose oral vitamin A , given on hospital admission to 592 children aged 1–59 months with moderate and severe pneumonia . Severely underweight children were not included , but 45 % were moderately underweight . The vitamin A and placebo groups were comparable in baseline characteristics . Four patients died . Among all of the surviving children , no differences were found regarding mean time for normalization of fever , respiratory rate and time of hospitalization . Stratification for moderate malnutrition , degree of pneumonia , age and sex revealed moderately malnourished vitamin A‐supplemented children to have a shorter time of hospitalization ( p= 0 . 04 ) , due to an effect in females aged > 12 months ( p= 0 . 02 ) and females with very severe pneumonia ( p= 0 . 048 ) . This study indicates that , in developing countries like Vietnam , supplementation with vitamin A in children with pneumonia could shorten the recovery rate in the ones that are undernourished , especially females > 1 y old Abstract Objective : To assess the impact of vitamin A supplementation on morbidity from acute respiratory tract infections and diarrhoea . Design : Double blind r and omised placebo controlled field trial . Setting : An urban slum area in New Delhi , India . Subjects—900 children aged 12 - 60 months attending a local health facility for acute diarrhoea of less than seven days ' duration r and omly allocated to receive vitamin A 200000 IU or placebo . Main outcome measures : Incidence and prevalence of acute lower respiratory tract infections and diarrhoea during the 90 days after termination of the enrolment diarrhoeal episode measured by twice weekly household surveillance . Results : The incidence ( relative risk 1.07 ; 95 % confidence interval 0.92 to 1.26 ) and average number of days spent with acute lower respiratory tract infections were similar in the vitamin A supplementation and placebo groups . Among children aged 23 months or less there was a significant reduction in the incidence of measles ( relative risk 0.06 ; 95 % confidence interval 0.01 to 0.48 ) . The incidence of diarrhoea was also similar ( relative risk 0.95 ; 0.86 to 1.05 ) in the two groups . There was a 36 % reduction in the mean daily prevalence of diarrhoea associated with fever in the vitamin A supplemented children older than 23 months . Conclusions : Results were consistent with a lack of impact on acute lower respiratory tract related mortality after vitamin A supplementation noted in other trials and a possible reduction in the severity of diarrhoea Role of micronutrients namely vitamin A , zinc and folate , as adjunct therapy of illness episodes in children in developing countries have been discussed in the light of health policy . Apart from a selective review , attempts have been made to statistically combine results of several studies to address policy issues . In children , vitamin A supplementation during illness has ( a ) a profound effect in reducing mortality in measles , ( b ) possibly a significant effect in reducing persistent diarrhea episodes in children with acute diarrhea , and ( c ) no benefit in pneumonia . Use of large dose vitamin A is recommended during measles episodes but not in non-measles pneumonia . Its use in acute diarrhea is debatable but recommended in persistent diarrhea and in severe malnutrition as a component of a micronutrient mixture . Large dose vitamin A supplementation should be used with caution in young infants as there are unresolved concerns about its safety particularly , bulging fontanelle observed in infants when co-administered at immunization . In children , zinc supplementation during illness , ( a ) had a marked effect in reducing prolonged episodes and a modest effect on episode duration in acute diarrhea , ( b ) result ed in reduced rate of treatment failure and death in persistent diarrhea , ( c ) had no effect in measles and non-measles pneumonia , and ( d ) probably had a detrimental effect of increasing death rate when a large dose was used in severely malnourished children . The desirability of routine zinc supplementation therapy of undernourished children with acute diarrhea should be assessed further . Concerning policy , zinc supplementation as a component of a micronutrient mixture is recommended in the rehabilitation of severely malnourished children and in persistent diarrhea . However , recommendation for its routine use in all cases of acute diarrhea in children needs additional studies on effectiveness , cost , operations and safety . In two r and omized controlled trials folate has been evaluated in acute and persistent diarrhea and found to have no beneficial effect . Folate is not recommended as adjunct therapy of diarrhea . Role of folate in preventing severe disease and /or death deserves further evaluation OBJECTIVE To determine whether vitamin A supplementation at birth could reduce infant morbidity and mortality . STUDY DESIGN We conducted a placebo-controlled trial among 2067 Indonesian neonates who received either 52 micromol ( 50,000 IU ) orally administered vitamin A or placebo on the first day of life . Infants were followed up at 1 year to determine the impact of this intervention on infant mortality . A subgroup ( n = 470 ) was also examined at 4 and 6 months of age to examine the impact on morbidity . RESULTS Vital status was confirmed in 89 % of infants in both groups at 1 year . There were 19 deaths in the control group and 7 in the vitamin A group ( relative risk = 0.36 ; 95 % confidence interval = 0.16 , 0.87 ) . The impact was stronger among boys , infants of normal compared with low birth weight , and those of greater ponderal index . Among infants examined at 4 months of age , the 1-week period prevalence of common morbidities was similar for vitamin A and control infants . However , during this same 4-month period , 73 % and 51 % more control infants were brought for medical treatment for cough ( p = 0.008 ) and fever ( p = 0.063 ) , respectively . CONCLUSIONS Neonatal vitamin A supplementation may reduce the infant mortality rate and the prevalence of severe respiratory infection among young infants OBJECTIVE To determine whether plasma vitamin A levels are associated with immunologic status and clinical outcome during human immunodeficiency virus type 1 ( HIV-1 ) infection . PATIENTS AND METHODS Analysis of vitamin A levels , CD4 T cells , complete blood cell count , and serologic markers for liver disease in a r and om sub sample of 179 subjects from a cohort of more than 2000 intravenous drug users with longitudinal follow-up to determine survival . RESULTS Mean ( + /- SE ) follow-up time was 22.8 + /- 1.1 months , and 15 subjects died during follow-up . More than 15 % of the HIV-1-seropositive individuals had plasma vitamin A levels less than 1.05 mumol/L , a level consistent with vitamin A deficiency . The HIV-1-seropositive individuals had lower mean plasma vitamin A levels than HIV-1-seronegative individuals ( P < .001 ) . Vitamin A deficiency was associated with lower CD4 levels among both seronegative individuals ( P < .05 ) and seropositive individuals ( P < .05 ) . In the HIV-seropositive participants , vitamin A deficiency was associated with increased mortality ( relative risk = 6.3 ; 95 % confidence interval , 2.1 to 18.6 ) . CONCLUSION Vitamin A deficiency may be common during HIV-1 infection , and vitamin A deficiency is associated with decreased circulating CD4 T cells and increased mortality . Vitamin A is an essential micronutrient for normal immune function , and vitamin A deficiency seems to be an important risk factor for disease progression during HIV-1 infection OBJECTIVE To test the efficacy of a high dose of vitamin A as adjuvant treatment for radiographically confirmed cases of acute lower respiratory tract infection ( ALRI ) . DESIGN R and omized , double-masked , placebo-controlled clinical trial . SETTING Two large urban hospitals in Guatemala City . PATIENTS Sequential sample of 263 children aged 3 to 48 months , identified in the emergency departments and admitted to the hospital . INTERVENTIONS Vitamin A ( 100,000 IU for children less than 1 year of age , and 200,000 IU for older children ) or placebo in addition to st and ard treatment for ALRI which included antibiotics , oxygen , bronchodilators , and intravenously administered solutions . MEASUREMENTS AND MAIN RESULTS The children were assessed every 8 hours . There were neither statistically nor clinical ly significant differences by treatment group in the rate of normalization in respiratory rate , oxygen saturation , temperature , or clinical score . Duration of hospitalization was not different by treatment group . Adverse outcomes ( mechanical ventilation , prolonged hospitalization , readmission or transfer , and death ) were equally distributed between the two groups . CONCLUSIONS Treatment with high doses of vitamin A over and above st and ard care for infants and children with non-measles-related ALRI is not efficacious for the current episode . Additional trials among population s in which vitamin A deficiency is more prevalent and severe should be considered The effect of vitamin A supplementation on preschool child morbidity and mortality was assessed in a prospect i ve double-blind placebo-controlled study around Hyderabad , India . Every six months 200,000 IU vitamin A was given to 7691 children ( treatment group ) whereas 8084 children received a placebo ( control group ) . Morbidity and mortality data were collected every three months . Risk of respiratory infection was higher in children with mild xerophthalmia than in children with normal eyes . Vitamin A supplementation had no effect on morbidity status . Mortality rates were similar in the two groups ; it was highest in children who did not receive either vitamin A or placebo . The findings suggest that vitamin A supplementation alone may not reduce child mortality Although most studies on the effect of vitamin A supplementation have reported reductions in childhood mortality , the effects on morbidity are less clear . We have carried out two double-blind , r and omised , placebo-controlled trials of vitamin A supplementation in adjacent population s in northern Ghana to assess the impact on childhood morbidity and mortality . The Survival Study included 21,906 children aged 6 - 90 months in 185 geographical clusters , who were followed for up to 26 months . The Health Study included 1455 children aged 6 - 59 months , who were monitored weekly for a year . Children were r and omly assigned either 200,000 IU retinol equivalent ( 100,000 IU under 12 months ) or placebo every 4 months ; r and omisation was by individual in the Health Study and by cluster in the Survival Study . There were no significant differences in the Health Study between the vitamin A and placebo groups in the prevalence of diarrhoea or acute respiratory infections ; of the symptoms and conditions specifically asked about , only vomiting and anorexia were significantly less frequent in the supplemented children . Vitamin-A-supplemented children had significantly fewer attendances at clinics ( rate ratio 0.88 [ 95 % CI 0.81 - 0.95 ] , p = 0.001 ) , hospital admissions ( 0.62 [ 0.42 - 0.93 ] , p = 0.02 ) , and deaths ( 0.81 [ 0.68 - 0.98 ] , p = 0.03 ) than children who received placebo . The extent of the effect on morbidity and mortality did not vary significantly with age or sex . However , the mortality rate due to acute gastroenteritis was lower in vitamin-A-supplemented than in placebo clusters ( 0.66 [ 0.47 - 0.92 ] , p = 0.02 ) ; mortality rates for all other causes except acute lower respiratory infections and malaria were also lower in vitamin A clusters , but not significantly so . Improving the vitamin A intake of young children in population s where xerophthalmia exists , even at relatively low prevalence , should be a high priority for health and agricultural services in Africa and elsewhere Background . The goal of the trial was to determine the efficacy of a multicomponent acellular pertussis vaccine against Bordetella illnesses in comparison with a whole-cell product and DT . Design . In a r and omized , double-blind fashion , 2- to 4-month-old infants received 4 doses of either DTP or DTaP vaccine at 3 , 4.5 , 6 , and 15 to 18 months of age . The controls received 3 doses ( 3 , 4.5 , 15 to 18 months of age ) of DT vaccine . The DTP vaccine was Lederle adsorbed vaccine ( licensed in the United States ) and DTaP was Lederle/Takeda adsorbed vaccine . Follow-up for vaccine efficacy started 2 weeks after the third dose ( DTP/DTaP ) and at the same age ( 6.5 months ) in DT recipients . Reactogenicity of all doses of all three vaccines was documented by st and ardized parent diary cards . In addition , all subjects were monitored for respiratory illnesses and serious adverse events by biweekly phone calls . Results . From May 1991 to January 1993 , a total of 10 271 infants were enrolled : 8532 received either DTP or DTaP and 1739 received DT . Specific efficacy against B pertussisinfections with cough ≥7 days duration was 83 % ( 95 % confidence interval [ CI ] : 76–88 ) and 72 % ( 95 % CI : 62–79 ) for DTP and DTaP , respectively ; results for DTP and DTaP based on ≥21 days of cough with either paroxysms , whoop or posttussive vomiting ( PWV ) were 93 % ( 95 % CI : 89–96 ) and 83 % ( 95 % CI : 76–88 ) , respectively . For DTaP vaccine , efficacy was higher after the fourth dose as compared with its efficacy after the third dose ( 78 % vs 62 % for cough ≥7 days and 85 % vs 76 % for cough ≥21 days with PWV ) . For DTP vaccine , efficacy was less varied after the third and fourth dose ( 78 % vs 85 % for cough ≥7 days and 93 % vs 93 % for cough ≥21 days with PWV ) . In contrast with DTP , the DTaP vaccine had some efficacy against B parapertussisinfection ( point estimate for cough ≥7 days : 31 % [ 95 % CI : −10–56 ] ) . All vaccines were generally well-tolerated . However , side reactions were significantly less after DTaP compared with DTP . Conclusions . Like other multicomponent acellular pertussis vaccines , the Lederle/Takeda DTaP vaccine demonstrated good efficacy against mild and typical pertussis due to B pertussisinfections . Interestingly , it also may have some efficacy againstB parapertussis . Based on the results of this trial , the vaccine was licensed in the United States in December 1996 for all 5 doses of the currently recommended immunization schedule in this country BACKGROUND Treatment with high dose vitamin A reduces complications and duration of hospitalization for children with measles . In respiratory syncytial virus ( RSV ) infection , as with measles , low serum vitamin A concentrations correlate with increased severity of illness . METHODS To determine whether high dose vitamin A treatment is also effective for treating RSV disease , we conducted a r and omized , double blind , placebo-controlled trial among 180 RSV-infected children between 1 month and 6 years of age at three hospitals in Santiago , Chile . Children with nasal washes positive for RSV antigen were given oral vitamin A ( 50,000 to 200,000 IU of retinyl palmitate , doses according to age ; n = 89 ) or placebo ( n = 91 ) within 2 days of admission . RESULTS There was no significant benefit from vitamin A treatment for the overall group in duration of hospitalization , need for supplemental oxygen or time to resolve hypoxemia . For the subgroup of children with significant hypoxemia on admission ( room air oxygen saturation level < or = 90 % ) , those given vitamin A had more rapid resolution of tachypnea ( P = 0.01 ) and a shorter duration of hospitalization ( 5.5 vs. 9.3 days , P = 0.09 ) . No toxicities were seen , including excess vomiting or bulging fontanel . CONCLUSIONS If vitamin A has a beneficial effect on the course of RSV disease , it may be seen only in more severely ill children One hundred and seventy-two 0.5 - 3.0-year-old children in a mountainous area of northern Hebei Province of China were r and omly assigned to a vitamin A supplementation group ( n = 98 ) or a control group ( n = 74 ) for a 1 year double-blind study . Capsules containing 200,000 IU vitamin A and 40 IU vitamin E were given to the children in the experimental group 3 and 9 months after baseline examination . During the 12 month study period , there was a significant reduction in the incidence of diarrhoea ( P < 0.01 ) and respiratory disease ( P < 0.01 ) in the children of the experimental group compared to the control . Risk of diarrhoea and respiratory disease were respectively 2.5 and 3.4 times higher in the control children . Serum retinol and IgA levels of the treatment group were significantly higher than that of control group ( P < 0.01 ) 7 weeks after first supplementation . There was no significant difference in saliva IgA level between groups . No significant differences in growth were observed . It was concluded that supplementation with large doses of vitamin A decreased the incidence and severity of diarrhoea and respiratory disease in these children , possibly through enhanced activity of the immune system , but had no effect on growth over 1 year Abstract Objective : To evaluate the impact on clinical recovery and severity of the addition of large doses of vitamin A to the st and ard treatment for childhood pneumonia . Design : A r and omised , double blind , placebo controlled trial . Setting : Study children were recruited at a public hospital in Recife , north east Brazil , an area of marginal vitamin A deficiency . Subjects : 472 children aged 6 to 59 months with clinical diagnosis of pneumonia . Interventions : 200 000 IU ( infants ) or 400 000 IU ( 1 - 4 year olds ) of vitamin A in oil or similar capsules of placebo divided into two daily oral doses , in addition to the st and ard treatment . Main outcome measures : Duration of the episode and incidence of adverse outcomes . Results : The groups were similar with respect to overall duration of pneumonia and incidence of adverse outcomes . Children who received vitamin A , however , were less likely to have fever by day 3 ( P=0.008 ) and were 29 % less likely to fail to respond to the first line antibiotic ( P=0.054 ) . Conclusion : There was little evidence for an effect of vitamin A treatment on the immediate outcome of the pneumonia episode . Key messages Pneumonia is a leading cause of childhood mortality in developing countries Vitamin A supplementation has no impact on mortality from pneumonia even though it reduces overall mortality Treatment of measles pneumonia with vitamin A reduces case fatality and severity of disease This study showed that vitamin A treatment has no impact on the recovery from non-measles pneumonia , despite some suggestion that severely affected patients may benefit The addition of vitamin A for treatment protocol s for childhood pneumonia is not recommended for clinical cure , although it maybe a useful contact to improve vitamin A BACKGROUND High dose vitamin A therapy is effective in reducing morbidity and mortality associated with measles infection . Children with acute respiratory syncytial virus ( RSV ) infection have low serum vitamin A concentrations . METHODS We performed a multicenter , r and omized , placebo-controlled trial of high dose vitamin A therapy among 239 children 1 month to 6 years of age to determine whether high dose vitamin A therapy would reduce morbidity associated with RSV infection . RESULTS There were no differences between the vitamin A and placebo recipients for most clinical outcomes ; however , vitamin A recipients had-longer hospital stays than placebo recipients ( 5.0 days vs. 4.4 days , P = 0.01 ) after enrollment . This effect was significant for children who were older than 1 year ( who also had received the highest doses of vitamin A ) , particularly among those at low risk for complications of RSV infection and those enrolled during the second study season . Serum retinol levels at enrollment were inversely correlated with severity of illness . CONCLUSIONS We found no evidence of a beneficial effect of vitamin A for the treatment of RSV infection in children in the United States . There may be groups of children for which vitamin A has an adverse effect , result ing in longer hospital stays OBJECTIVES To determine whether vitamin A supplements result in reduced mortality among HIV-infected and uninfected children . DESIGN R and omized , double blind , placebo-controlled trial . METHODS Starting in April , 1993 , we r and omized 687 children age 6 months to 5 years who were admitted to the hospital with pneumonia . Children who were severely malnourished or had clinical signs of vitamin A deficiency were excluded . At baseline children received placebo or 400 000 IU ( or half that for infants ) of vitamin A , in addition to st and ard treatment for pneumonia . They received further doses of the same regimen 4 and 8 months after hospital discharge . Sera from children were tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot tests . For positive children < 15 months of age , HIV infection was confirmed by amplified heat-denatured HIV-p24 antigen assays with confirmatory neutralization assays . HIV status was ascertained for 648 of 687 enrolled children . The mean duration of follow-up was 24.4 months ( SD = 12.1 ) . RESULTS Of 648 children 58 ( 9 % ) were HIV-infected . Compared with uninfected children , all-cause mortality was higher among HIV-infected children , as was mortality caused by pneumonia or diarrhea ( P < 0.001 for each ) . Overall vitamin A supplements result ed in a 49 % reduction in mortality [ relative risk ( RR ) , 0.51 ; 95 % confidence interval ( CI ) , 0.29 to 0.90 , P = 0.02 ] . Vitamin A supplements reduced all-cause mortality by 63 % among HIV-infected children ( RR 0.37 ; CI 0.14 to 0.95 , P = 0.04 ) and by 42 % among uninfected children ( RR 0.58 , CI 0.28 to 1.19 , P = 0.14 ) . Vitamin A supplements were also associated with a 68 % reduction in AIDS-related deaths ( P = 0.05 ) and a 92 % reduction in diarrhea-related deaths ( P = 0.01 ) . CONCLUSION Vitamin A deficiency , which is common among children in many developing countries , is particularly severe among HIV-infected children . Our findings indicate that vitamin A supplements , a low cost intervention , reduce mortality of HIV-infected children STUDY OBJECTIVE To evaluate the relationship between vitamin A supplementation , plasma retinol level ( PRL ) and incidence , severity and duration of acute respiratory infect ions ( ARI ) in children 1 - 5 years old . DESIGN AND SETTING A one year prospect i ve r and omized intervention study from June 1989 to May 1990 in Cikutra , a suburb of B and ung , Indonesia . SUBJECTS AND MEASUREMENTS Out of almost 2000 children aged 12 - 54 months , 269 were selected by stratified r and omization . Vitamin A ( 200,000 IU orally ) was administered at 6-monthly intervals in a double blind , placebo controlled programme . Every 2 weeks , primary health care workers collected data on respiratory symptoms in the children , and every month a pediatrician examined the children . Venous blood sample s were obtained at the start and at 3 and 6 months for plasma retinol levels ( PRL ) . RESULTS The mean PRL at the start of the study was 20 + /- 8 micrograms/dl ; 8 % of the children showed a deficient level of less than 10 micrograms/dl . The incidence or ARI was 6.7 + /- 3.5 episodes per child per year with a mean duration of 5.3 + /- 3.1 days per episode . In vitamin A supplemented children the duration of ARI was slightly shorter ( 5.2 + /- 3.1 versus 5.6 + /- 3.1 days , P < 0.01 ) but no effect on the incidence or severity of ARI was detected . Low , and especially deficient , PRL had improved after 3 months and even after 6 months , but this was unrelated to vitamin A supplementation . There was also no relationship between PRL and incidence , severity or duration of ARI . CONCLUSIONS Only a slight relationship is found between vitamin A supplementation and ARI duration in under-fives |
2,277 | 27,117,012 | Limited evidence supported the positive effects of short-lever elastic knee braces to improve pain and functional disability in specific outcomes .
No evidence was found to support the use of foot orthoses , such as laterally wedged insoles , medial arch support and metatarsal arch pad .
Conclusion : Our systematic review found no conclusive evidence about the effectiveness of any braces and orthoses for patients with medial knee osteoarthritis .
Clinical relevance This is the first systematic review of Japanese- language r and omised controlled trials investigating orthoses for patients with knee osteoarthritis .
Clinicians can consider the use of short-lever elastic knee braces to improve specifically pain on squat or walking .
Evidence found in this review does not support the use of foot orthoses | Background : Knee osteoarthritis is common .
The evidence regarding the effectiveness of braces and orthoses for patients with knee osteoarthritis is inconclusive according to English- language literature .
English- language review s to date have not included Japanese- language studies .
Objectives : This study aim ed to collect and synthesis e Japanese- language r and omised controlled trials investigating the effectiveness of braces and orthoses for patients with knee osteoarthritis . | Evidence -based practice involves the use of evidence from systematic review s and r and omised controlled trials , but the extent of this evidence in physiotherapy has not previously been surveyed . The aim of this survey is to describe the quantity and quality of r and omised controlled trials and the quantity of systematic review s relevant to physiotherapy . The Physiotherapy Evidence Data base ( PEDro ) was search ed . The quality of trials was assessed with the PEDro scale . The search identified a total of 2,376 r and omised controlled trials and 332 systematic review s. The first trial was published in 1955 and the first review was published in 1982 . Since that time , the number of trials and review s has grown exponentially . The mean PEDro quality score has increased from 2.8 in trials published between 1955 and 1959 to 5.0 for trials published between 1995 and 1999 . There is a substantial body of evidence about the effects of physiotherapy . However , there remains scope for improvements in the quality of the conduct and reporting of clinical trials Background Osteoarthritis ( OA ) is a degenerative disease , considered to be one of the major public health problems . Research suggests that patient education is feasible and valuable for achieving improvements in quality of life , in function , well-being and improved coping . Since 1994 , Primary Health Care in Malmö has used a patient education programme directed towards OA . The aim of this study was to evaluate the effects of this education programme for patients with OA in primary health care in terms of self-efficacy , function and self-perceived health . Method The study was a single-blind , r and omized controlled trial ( RCT ) in which the EuroQol-5D and Arthritis self-efficacy scale were used to measure self-perceived health and self-efficacy and function was measured with Grip Ability Test for the upper extremity and five different functional tests for the lower extremity . Results We found differences between the intervention group and the control group , comparing the results at baseline and after 6 months in EuroQol-5D ( p < 0.001 ) and in st and ing one leg eyes closed ( p = 0.02 ) in favour of the intervention group . No other differences between the groups were found . Conclusion This study has shown that patient education for patients with osteoarthritis is feasible in a primary health care setting and can improve self-perceived health as well as function in some degree , but not self-efficacy . Further research to investigate the effect of exercise performance on function , as well as self-efficacy is warranted . Trial registration The trial is registered with Clinical Trials.gov . Registration number : OBJECTIVE To assess the effect of an insole with subtalar strapping on patients with medial compartment osteoarthritis ( OA ) of the knee . METHODS Novel lateral wedged insoles with elastic subtalar strapping ( the subtalar strapping support group ) and ankle supporters with a lateral wedged heel insert ( the sock-type ankle support group ) were prepared . Eighty-eight female out patients with knee OA were treated with 1 of the 2 insoles for 8 weeks . Femorotibial angle was assessed by st and ing radiographs with and without unilateral insole use for each subject . Symptoms of knee OA were evaluated according to the severity index of Lequesne et al at baseline and at the final assessment . RESULTS Participants wearing the insole with subtalar strapping ( n = 42 ) demonstrated significantly decreased femorotibial angle ( an average of change : -3.1 degrees + /- 2.5 degrees , P < 0.0001 ) , but a significant difference was not found in the sock-type ankle support group ( n = 46 ; -0.4 degrees + /- 1.1 degrees , P > 0.05 ) . In the subtalar strapping support group , pain during bed rest with full extension of the knee ( P < 0.0001 ) , pain after getting up ( P = 0.04 ) , pain on getting up from a seated position ( P = 0.021 ) , maximum distance walked ( P = 0.009 ) , and aggregate severity score ( P < 0.0001 ) were significantly improved compared with baseline . In contrast , significant symptomatic improvement was detected only in the aggregate score ( P = 0.016 ) in the sock-type ankle support group , but not in any of the 10 specific categories . CONCLUSION The lateral wedged insole with subtalar strapping induces correction of the femorotibial angle and symptomatic relief in patients with varus-deformity knee OA R and omized controlled trials often suffer from two major complications , i.e. , noncompliance and missing outcomes . One potential solution to this problem is a statistical concept called intention-to-treat ( ITT ) analysis . ITT analysis includes every subject who is r and omized according to r and omized treatment assignment . It ignores noncompliance , protocol deviations , withdrawal , and anything that happens after r and omization . ITT analysis maintains prognostic balance generated from the original r and om treatment allocation . In ITT analysis , estimate of treatment effect is generally conservative . A better application of the ITT approach is possible if complete outcome data are available for all r and omized subjects . Per- protocol population is defined as a subset of the ITT population who completed the study without any major protocol violations Lateral wedges were originally proposed to manage medial compartment osteoarthritis of the knee but recent review s suggest that lateral wedges do not affect disease progression . We performed a systematic review to analyse the recent literature and define how effective , if at all , lateral wedges are in the management of medial compartment osteoarthritis of the knee . The inclusion criteria were defined as any study published within the last decade , using a sample size of at least twenty patients , and investigating the effect of insoles or wedges on either unilateral or bilateral knee varus osteoarthritis . The st and ardised keyword term ‘ lateral*wedge*OR insole*OR orthotic * OR medial compartment OR varus OR osteoarthri * OR knee * ’ was used . We identified 10 studies that fitted our inclusion criteria . Although there is not enough evidence in the literature to prove that lateral wedge orthotics are an effective treatment for varus osteoarthritis of the knee , there is some evidence to suggest that they do have some symptomatic effect . Patients with early osteoarthritis and higher BMI may benefit to a greater extent than those with a greater extent of degenerative changes and lower BMI . The literature is unclear as to what the optimal duration for the use of lateral wedges is , but does support the prolonged use of the wedges as the benefits at one month are maintained at one year . Future studies should be r and omised controlled trials with a large sample size with long follow-up , and use objective clinical , biomechanical and radiological outcome measures The index for hip disease ( ISH ) was established , vali date d and appraised as a new assessment test for the trial of new drugs as well as for long-term follow-up of patients , and to help with future indications for surgery . The ISH deals with pain , maximum walking distance , and some activities of daily living . Inter-observer reproducibility is good ( mean deviation 0.55 points ; p less than 0.05 ) . In a short-term , double-blind crossover trial , the ISH , judged according to its power to distinguish between the active drug period and the placebo period , appears as one of the best assessment tests . In the long term , total hip prosthesis is most often justified when the ISH score reaches 10 - 12 points . The index of severity for knee disease ( ISK ) was vali date d and appraised by the same statistical methods . Its value in non-steroidal anti-inflammatory drug ( NSAID ) or analgesic trials is lower than the value of the ISH . However , its use is still justified for that purpose , and for long-term follow-up of osteoarthritis of the knee OBJECTIVES To identify factors that predicted incident use of assistive walking devices ( AWDs ) and to explore whether AWD use was associated with changes in osteoarthritis of the knee . DESIGN Prospect i ve cohort study . SETTING Community . PARTICIPANTS Older adults ( N=2639 ) in the Health , Aging and Body Composition ( Health ABC ) Study including a subset of 874 patients with prevalent knee pain . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Incident use of AWDs , mean Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain scores , and the frequency of joint space narrowing on knee radiographs over a 3-year time period . RESULTS AWD use was initiated by 9 % of the entire Health ABC cohort and 12 % of the knee pain subset . Factors that predicted use in both groups were age ≥73 ( entire cohort : odds ratio [OR]=2.07 ; 95 % confidence interval [ CI ] , 1.43 - 3.01 ; knee pain subset : OR=1.87 ; 95 % CI , 1.16 - 3.03 ) , black race ( entire cohort : OR=2.95 ; 95 % CI , 2.09 - 4.16 ; knee pain subset : OR=3.21 ; 95 % CI , 2.01 - 5.11 ) , and lower balance ratios ( entire cohort : OR=3.18 ; 95 % CI , 2.21 - 4.59 ; knee pain subset : OR=3.77 ; 95 % CI , 2.34 - 6.07 ) . Mean WOMAC pain scores decreased slightly over time in both AWD and non-AWD users . Twenty percent of non-AWD users and 28 % of AWD users had radiographic progression in joint space narrowing of the tibiofemoral joint in at least 1 knee . Fourteen percent of non-AWD users and 12 % of AWD users had radiographic progression in joint space narrowing in the patellofemoral joint in at least 1 knee . CONCLUSIONS AWDs are frequently used by older adults . Knee pain and balance problems are significant reasons why older adults initiate use of an AWD . In an exploratory analysis , there was no consistent relation between the use or nonuse of an AWD and WOMAC pain scores or knee joint space narrowing progression . Further studies of the relation of use of AWDs to changes in knee osteoarthritis are needed OBJECTIVE To assess the contribution of radiological osteoarthritis of the hips and knees to disabilities in the activities of daily living related to lower limb function . METHODS During a home interview 1156 men and 1739 women , r and omly chosen from the source population of all independently living residents aged 55 years and over living in a district of Rotterdam ( the Rotterdam Study ) were asked about locomotor disability by six questions of the Health Assessment Question naire ( HAQ ) and about pain in the hips and knees in the past month . Radiographs of hips and knees were scored according to the Kellgren grading system for osteoarthritis . RESULTS The prevalence of locomotor disability , defined as at least some difficulty with three or more out of six lower limb functions , was 20.2 % for men and 31.9 % for women ; hip pain was present in 8.3 % of the men and 16.6 % of the women ; knee pain in 12.6 % of the men and 22.3 % of the women . The prevalence of radiological osteoarthritis grade 2 + of the hip was 14.1 % for men and 15.9 % for women , and of the knee 16.3 % and 29.1 % respectively . The odds ratio ( OR ) ( 95 % confidence intervals ) of hip radiological osteoarthritis for locomotor disability adjusted for age and all other variables was for men : 1.4 ( 0.9 , 2.1 ) and for women : 2.2 ( 1.6 , 2.9 ) . The ORs of knee radiological osteoarthritis adjusted for age and all other variables were 1.1 ( 0.9 , 2.1 ) and 1.4 ( 1.1 , 1.8 ) respectively . Severe radiological osteoarthritis ( grade 3 + ) was stronger associated . The ORs of pain in the hips or knees and morning stiffness were much higher ( between 2.7 and 5.5 for men and between 2.1 and 5.1 for women ) . CONCLUSIONS Radiological osteoarthritis of the hip and knee are only weak independent predictors of locomotor disability in women , and not at all independently associated with locomotor disability in men . Age , pain of the hips and knees , and morning stiffness seem to be the most important independent determinants of locomotor disability Overemphasis on hypothesis testing-- and the use of P values to dichotomise significant or non-significant results --has detracted from more useful approaches to interpreting study results , such as estimation and confidence intervals . In medical studies investigators are usually interested in determining the size of difference of a measured outcome between groups , rather than a simple indication of whether or not it is statistically significant . Confidence intervals present a range of values , on the basis of the sample data , in which the population value for such a difference may lie . Some methods of calculating confidence intervals for means and differences between means are given , with similar information for proportions . The paper also gives suggestions for graphical display . Confidence intervals , if appropriate to the type of study , should be used for major findings in both the main text of a paper and its abstract The prevalence of osteoarthritis ( OA ) is greater in women then men . Weight , a factor strongly associated with osteoarthritis , is significantly increased over the menopausal transition . Despite the high prevalence of osteoarthritis , a disabling disease with limited treatment options , there is a paucity of studies in women . The longitudinal phase of the Melbourne Women 's Midlife Health Project , is a population -based prospect i ve study of 438 Australian born women who have been followed annually over 11 years . 257 ( 59 % ) of these women remained in longitudinal assessment at 11th year of follow-up and 224 of these women agreed to undergo X-rays of their knees and h and s. In this study , X-rays were scored for evidence of osteoarthritis using a vali date d scale , by two investigators who were blinded to question naire results . Information on hormone therapy use , physical activity , smoking , BMI and age were obtained by both self-administered and face-to-face question naires . Results showed that one hundred and twenty-eight women ( 56 % ) had evidence of radiological OA . Forty-nine ( 21.6 % ) had evidence of radiological knee OA . One hundred and one ( 44.5 % ) had evidence of radiological h and OA . Compared to baseline , at 11th year of follow-up participants had put on weight ( 4 kg range -14 to 25 kg ) and a larger proportion ( 25 % vs. 40 % ) reported exercising frequently ( P = 0.005 ) . Physical activity and BMI were associated with higher prevalence of osteoarthritis in the final year of follow-up . Smoking was associated with a lower prevalence of radiological knee OA . The prevalence was 61 % among never smokers compared to only 39 % among those who smoked ( P < 0.05 ) . Total OA was associated with never having used hormone therapy ( odds ratio 2.7 ; CI 1.1 - 6.9 ) . There was a trend for increasing level of physical activity at ages 20 - 29 to be associated with an increased risk of knee OA ( P value 0.03 for trend ) . In conclusion increasing age , BMI and history of more frequent physical activity in younger years were risk factors for radiological knee OA . In contrast , smoking appeared to be associated with less knee OA . Never having used hormone therapy was a risk factor for radiological h and and knee OA . Further work will be needed to determine whether modification of these factors can prevent the development of OA OBJECTIVE To evaluate the effect of a brace intended to reduce load in patients with medial or lateral compartmental osteoarthritis ( OA ) and concurrent varus or valgus alignment , respectively . DESIGN This multi-centre r and omized controlled trial ( performed 2001 - 2003 ) studies the additive effect of a brace intended to reduce load in conservative treatment of unicompartmental OA of the knee . SETTING Orthopedic department of a university medical centre and of one general hospital . The follow-up was 12 months . PATIENTS 117 patients with unicompartmental OA of the knee . Intervention group ( n=60 ) comprising conservative treatment with additional brace treatment and a control group ( n=57 ) comprising conservative treatment alone . PRIMARY OUTCOME MEASURES Pain severity and knee function score . SECONDARY OUTCOME MEASURES Walking distance and quality of life . ANALYSIS Multiple linear regression models according to the intention-to-treat-principle were used to assess outcome differences for the entire group of patients . In addition , we performed explorative subgroup analyses on primary overall outcomes stratified for alignment , degree of OA , origin of OA , and age . RESULTS Although the primary outcome measures were improved in the intervention group in comparison with the controls at each assessment point , the differences reached only borderline significance . The reported walking distances at 3 months , 12 months and overall were significantly longer in the brace group ( P=0.03 , P=0.04 and P=0.02 , respectively ) . Subgroup analysis showed a better effect in the varus group , in patients with severe OA , in patients with secondary OA and in patients younger then 60 years . In total 25 patients in the brace group and 14 in the control group changed their initial treatment , mostly ( 74 % ) because of a lack of beneficial effect . CONCLUSIONS The results indicate that a brace intended to reduce load shows small effects in patients with unicompartmental OA . However , many patients do not adhere in the long run to this kind of conservative treatment OBJECTIVE This study was conducted in order to assess the effect of wearing a lateral wedged insole with a subtalar strap for 2 years in patients with osteoarthritis varus deformity of the knee ( knee OA ) . DESIGN The setting was an outpatient clinic . The efficacies of the strapped insole and a traditional shoe insert wedged insole ( the inserted insole ) , as a positive control , were compared at the baseline and after 2 years of treatment . R and omization was performed according to birth date . The 61 female out patients with knee OA who completed a prior 6-month study were asked to wear their respective insoles continuously as treatment during the course of the 2-year study . The femorotibial angle ( FTA ) was assessed by st and ing radiographs obtained while the subjects were barefoot and the Lequesne index of the knee OA at 2 years was compared with those at baseline in each insole group . RESULTS There were 61 patients in the original study , but 13 patients ( 21.3 % ) did not want to wear the insole continuously and five ( 8.2 % ) withdrew for other reasons . The 42 patients who completed the 2-year study were evaluated . At the 2-year assessment , participants wearing the subtalar strapped insole ( n=21 ) demonstrated significantly decreased FTA ( P=0.015 ) , and significantly improved Lequesne index ( P=0.031 ) in comparison with their baseline assessment s. These significant differences were not found in the group with the traditional shoe inserted wedged insole ( n=21 ) . CONCLUSION Only those participants using the subtalar strapped insole demonstrated significant change in the FTA in comparison with the baseline assessment s. If the insole with a subtalar strap maintains FTA for more than 2 years , it may restrict the progression of degenerative articular cartilage lesions of knee OA OBJECTIVE To compare the influence of concomitant heeled footwear when wearing a lateral wedged insole for medial compartment of osteoarthritis ( OA ) of the knee , between everyday walking shoes for outdoor use and socks or flat footwear without a heel for indoor use . DESIGN A total of 227 out patients were prospect ively r and omized and treated with a neutral wedged insole inserted into shoes ( placebo with shoes ; n=45 ) , a wedged insole inserted into shoes ( inserted insole with shoes ; n=45 ) , a sock-type ankle supporter with a wedged insole when wearing socks or flat footwear ( inserted insole without shoes ; n=46 ) , a subtalar strapped insole when wearing shoes ( strapped insole with shoes ; n=45 ) , and the strapped insole with socks or flat footwear ( strapped insole without shoes ; n=46 ) . The Lequesne index of knee OA at week 12 was compared with the baseline in each treatment group . RESULTS Twenty patients withdrew from the study , and the 207 patients who completed the 12-week study were evaluated . At the final assessment , participants wearing the inserted insole without shoes ( P=0.003 ) , the strapped insole with shoes ( P<0.0001 ) , and the strapped insole without shoes ( P<0.0001 ) demonstrated significantly improved Lequesne index scores in comparison with their baseline assessment s. No significant differences were found in the placebo ( P=0.16 ) or the inserted insole with shoes ( P=0.2 ) groups . CONCLUSION Concomitant heeled footwear may decrease the efficacy of an inserted lateral wedged insole . The optimal usage of a lateral wedged insole for knee OA would be the combination with socks or flat footwear without heels OBJECTIVE We investigated the effects of celecoxib , diclofenac , and ibuprofen on the disease-specific quality of life , synovial fluid cytokines and signal transduction pathways in symptomatic knee osteoarthritis ( OA ) . DESIGN Ninety patients scheduled for a total knee arthroplasty ( TKA ) were r and omized to six groups that were treated with low and high dosages of celecoxib , diclofenac or ibuprofen . At the time of the first admission ( T0 ) and at surgery ( T1 = 14 days after beginning of the nonsteroidal anti-inflammatory drugs ( NSAIDs ) ) , sample s of knee synovial fluid were obtained from each patient for analysis . During the surgery the synovial tissue was harvested from the knee of patients . The Western Ontario and McMaster universities ( WOMAC ) score was used to evaluate the patient disease-specific quality of life at T0 and T1 . Microarray tests performed at T0 and T1 were used to evaluate the effects of NSAIDs on Tumor necrosis factor (TNF)-alpha , Interleukin-6 ( IL-6 ) , IL8 and Vascular endothelial growth factor ( VEGF ) concentration in the synovial fluid . Western blot assays evaluated the effects of NSAIDs on MAP kinase ( MAPK ) signal transduction pathway in the synovial membrane . RESULTS NSAID treatment induced a statistically significant improvement in the WOMAC score and a statistically significant decrease in the IL-6 , VEGF and TNF-alpha concentration in the synovial fluid . Higher dosages of NSAIDs provided a greater improvement in the disease-specific quality of life of patients and lower concentrations of pro-inflammatory cytokines in the synovial fluid . Inhibition of MAPKs was noted after NSAID treatment . CONCLUSION Short-term NSAID treatment improves the patient disease-specific quality of life with a parallel decrease in pro-inflammatory synovial fluid cytokine levels in knee OA . Signal transduction pathways may be involved in regulating the anti-inflammatory effects of NSAIDs . Clinical Trial.gov : NCT01860833 The relationship between osteoarthritis ( OA ) and osteoporosis remains controversial . This study was design ed to determine the association between hip and knee radiographic OA and change in total hip bone mineral density ( BMD ) over 2.6 years . A total of 867 population -based r and omly selected subjects ( mean age 62 years , range 51 to 80 years , and 49 % female ) were included . Hip and knee joint space narrowing ( JSN , 0 to 3 ) and osteophytes ( 0 to 3 ) in both lower limbs was assessed using Altman 's atlas . Total hip BMD was measured by dual-energy X-ray absorptiometry ( DXA ) . We found that radiographic OA ( score of JSN or osteophytes > 0 ) was common in this sample ( hip 45 % , knee 68 % ) . In multivariable analyses , percentage change in total hip BMD per year was predicted by right and left hip axial JSN ( beta = -0.25 % and -0.29 % per grade , respectively , both p < .05 ) , right hip superior femoral osteophytes ( grade s 2 and 3 versus 0 : beta = -1.60 , p < .05 ) , combined right and left knee tibiofemoral JSN ( beta = -0.06 per grade from grade s 0 to 12 , p < .05 ) , and osteophytes ( beta = -0.06 per grade from grade s 0 to 14 , p < .05 ) independent of each other and joint pain . In conclusion , older subjects with radiographic hip and knee OA have higher total hip bone loss over 2.6 years regardless of symptoms , suggesting that consideration should be given to the monitoring of bone mass in these subjects 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 . The WOMAC Osteoarthritis Index and Lequesne Algofunctional Index have not been translated and vali date d for Iranian patients with osteoarthritis ( OA ) of the knee or hip . The aim of this study was to vali date the Persian form of WOMAC OA Index and Lequesne Algofunctional Index and to assess their test – retest reliability and convergent validity . Forward/backward translations and consensus panels were conducted to obtain the Persian versions of WOMAC OA Index and Lequesne Algofunctional Index . A non-probability sample of 116 patients with knee/hip osteoarthritis was asked to complete the WOMAC OA Index and Lequesne Algofunctional Index as well as Medical Outcomes Study —20-Item Short Form ( SF-20 ) question naires , a visual analogue scales ( VAS ) of pain and demographic information form . Internal consistency ( using Cronbach ’s alpha ) and convergent validity ( by examining the Pearson ’s correlation coefficients ) were evaluated to determine the psychometric properties of the question naires . In order to evaluate test – retest reliability , 20 r and omly selected patients completed the question naires , on a second occasion , 7–10 days later . Cronbach ’s alpha coefficients and intraclass correlation coefficients for the WOMAC OA Index and Algofunctional Index subscales ranged from 0.63 to 0.94 and from 0.53 to 0.96 , respectively . Statistically significant correlations were found between WOMAC OA Index , Algofunctional Index and SF-20 subscales and VAS for pain . The Persian version of WOMAC demonstrated a more acceptable validity , internal consistency and reliability compared with the Lequesne Algofunctional Index . However , both indices are valid and reliable instruments for evaluating the OA severity of knee/hip in Iran OBJECTIVE To assess the effect of a lateral-wedge insole with elastic strapping of the subtalar joint on the femorotibial angle in patients with varus deformity of the knee . METHODS The efficacy of a wedged insole with subtalar straps and that of a traditional wedged insole shoe insert were compared . Sixty-six female out patients with knee osteoarthritis ( OA ) were r and omized ( according to birth date ) to be treated with either the strapped or the traditional inserted insole . St and ing radiographs with unilateral insole use were used to analyze the femorotibial angles for each patient . In both groups , the baseline and 6-month visual analog scale ( VAS ) scores for subjective knee pain and the Lequesne index scores for knee OA were compared . RESULTS The 61 patients who completed the 6-month study were evaluated . At baseline , there was no significant difference in the femorotibial angle ( P = 0.66 ) and the VAS score ( P = 0.75 ) between the 2 groups . At the 6-month assessment , the 29 subjects wearing the subtalar-strapped insole demonstrated a significantly decreased femorotibial angle ( P < 0.0001 ) and significantly improved VAS scores ( P = 0.001 ) and Lequesne index scores ( P = 0.033 ) compared with their baseline assessment s. These significant differences were not observed in the 32 subjects assigned to the traditional shoe-inserted wedged insole . CONCLUSION These results suggest that an insole with a subtalar strap maintained the valgus correction of the femorotibial angle in patients with varus knee OA for 6 months , indicating longer-term clinical improvement with the strapped insert compared with the traditional insert OBJECTIVE To assess the efficacy of a lateral wedge insole with elastic strapping of the subtalar joint for conservative treatment of osteoarthritis ( OA ) of the knee . METHODS The efficacy of a novel insole with elastic subtalar strapping and a traditional shoe insert wedge insole was compared . Ninety female out patients with OA of the knee were treated with wedge insoles for 8 weeks . R and omization was performed according to birth date . St and ing radiographs with unilateral insole use were used to analyze the femorotibial and talar tilt angles for each patient with and without their respective insole . Visual analog scale ( VAS ) score for subjective knee pain at the final assessment was compared with that at baseline in both groups . RESULTS Participants wearing the elastically strapped insole ( n = 46 ) had significantly decreased femorotibial angle ( p < 0.0001 ) and talar tilt angle ( p = 0.005 ) and significantly improved VAS pain score ( p = 0.045 ) in comparison with baseline assessment s. These significant differences were not found in the group with the inserted insole ( n = 44 ) . CONCLUSION The novel strapped insole leads to valgus angulation of the talus , result ing in correction of the femorotibial angle in patients with knee OA with varus deformity , and may have a therapeutic effect similar to that of high tibial osteotomy |
2,278 | 27,426,026 | MAIN RESULTS We included a total of 84 trials ( 22,872 participants ) , with 70/84 studies reporting interventions in higher risk individuals or setting s. Studies with follow-up periods of at least four months were of more interest in assessing the sustainability of intervention effects and were also less susceptible to short-term reporting or publication bias .
Subgroup analyses revealed no clear subgroup effects for longer-term outcomes ( four or more months ) for assessment only versus alternative intervention controls ; for university/college vs other setting s ; or for higher risk vs all/low risk participants .None of the studies reported harms related to MI .
AUTHORS ' CONCLUSIONS The results of this review indicate that there are no substantive , meaningful benefits of MI interventions for preventing alcohol use , misuse or alcohol-related problems . | BACKGROUND Alcohol use and misuse in young people is a major risk behaviour for mortality and morbidity .
Motivational interviewing ( MI ) is a popular technique for addressing excessive drinking in young adults .
OBJECTIVES To assess the effects of motivational interviewing ( MI ) interventions for preventing alcohol misuse and alcohol-related problems in young adults . | OBJECTIVE This study examined the effectiveness of three peer-facilitated brief alcohol interventions -small group motivational interviewing , motivationally enhanced peer theater , and an interactive alcohol-education program-with students engaging in high-risk drinking who were referred for alcohol policy violations . METHOD Undergraduate students referred for alcohol policy violations ( N = 695 ) at a large northeastern public university were r and omized to one of the three conditions . Six-month follow-up data were collected on drinking frequency and quantity , negative consequences , use of protective behaviors , and perceptions of peers ' drinking norms . RESULTS There were no statistically significant overall pre-post effects or treatment effects . However , exploratory analyses indicated that decreases in perceived norms and increases in use of protective behavioral strategies were associated with reductions in alcohol use and alcohol-related problems at follow-up ( p < .01 ) . CONCLUSIONS The presence of nonsignificant pre-post or main effects is , in part , consistent with recent research indicating that sanctioned college students may immediately reduce drinking in response to citation and that brief interventions may not contribute to additional behavioral change . The presence of statistically significant correlations between alcohol use and related problems with corrections in norms misperceptions and increased use of protective behaviors at the individual level holds promise for both research and practice . The integration of elements addressing social norms and use of protective behaviors within brief cognitive-behavioral intervention protocol s delivered by trained peer facilitators warrants further study using r and omized clinical trials AIM To establish the efficacy of a brief motivational intervention compared to feedback only when delivered in an emergency department for reducing alcohol use and problems among young adults . DESIGN Two-group r and omized controlled trial with follow-up assessment s at 6 and 12 months . SETTING Level I Trauma Center . PARTICIPANTS A total of 198 18 - 24-year-old patients who were either alcohol positive upon hospital admission or met screening criteria for alcohol problems . INTERVENTION Participants were assigned r and omly to receive a one-session motivational intervention ( MI ) that included personalized feedback , or the personalized feedback report only ( FO ) . All participants received additional telephone contact 1 month and 3 months after baseline . MEASUREMENTS Demographic information , alcohol use , alcohol problems and treatment seeking . FINDINGS Six months after the intervention MI participants drank on fewer days , had fewer heavy drinking days and drank fewer drinks per week in the past month than did FO patients . These effects were maintained at 12 months . Clinical significance evaluation indicated that twice as many MI participants as FO participants reliably reduced their volume of alcohol consumption from baseline to 12 months . Reductions in alcohol-related injuries and moving violations , and increases in alcohol treatment-seeking were observed across both conditions at both follow-ups with no differences between conditions . CONCLUSIONS This study provides new data supporting the potential of the motivational intervention tested to reduce alcohol consumption among high-risk youth AIMS This study aim ed at testing the effectiveness of a brief motivational intervention ( BI ) compared with a minimal intervention ( MI ) for reducing alcohol consumption in adult , alcohol-positive traffic casualties . METHODS Patients were recruited at the emergency room of a trauma hospital and screened for alcohol by a qualitative saliva test ( positive from a blood alcohol concentration of 0.02 g/l ) . Positive patients ( 13.3 % ) who accepted entering the study were r and omly allocated into BI and MI . Baseline assessment was the same for all patients . Blind telephone follow-ups were performed at months 3 , 6 , and 12 , and results were analysed by protocol and by intention-to-treat analysis . RESULTS After 1 year of follow-up , 67 % of the patients had reduced their consumption , the percentage of heavy drinkers had dropped by 47 % , and 62 % of baseline AUDIT-C positive patients ( hazardous drinkers ) had become negative . Binge drinking dropped significantly ( P < 0.05 ) . Results at month 12 were in line with the previous ones . CONCLUSIONS The effectiveness of BI compared with MI has not been verified , but a significant reduction in consumption has been observed in the whole sample , without significant differences by type of intervention . The persistence and dimension of changes suggest a real effect of both interventions , although the lack of a pure control group does not allow definitive conclusions . Traffic casualties are in a teachable moments to benefit from easy and cheap interventions This study tested the efficacy of behavioral treatments for alcohol use disorders ( AUD ) among men who have sex with men ( MSM ) and who are at risk for HIV transmission . HIV-negative MSM with current AUD ( N = 198 ) were recruited , offered treatment focused on reducing drinking and HIV risk , and followed during treatment and 12 months posttreatment . Participants ( n = 89 ) accepted treatment and were r and omized to either 4 sessions of motivational interviewing ( MI ) or 12 sessions of combined MI and coping skills training ( MI + CBT ) . Other participants ( n = 109 ) declined treatment but were followed , forming a non-help-seeking group ( NHS ) . MI yielded significantly better drinking outcomes during the 12-week treatment period than MI + CBT , but posttreatment outcomes were equivalent . NHS participants significantly reduced their drinking as well . Service delivery and treatment research implication s are discussed Group motivational interviewing ( MI ) interventions that target youth at-risk for alcohol and other drug ( AOD ) use may prevent future negative consequences . Youth in a teen court setting [ n=193 ; 67 % male , 45 % Hispanic ; mean age 16.6 ( SD=1.05 ) ] were r and omized to receive either a group MI intervention , Free Talk , or usual care ( UC ) . We examined client acceptance , and intervention feasibility and conducted a preliminary outcome evaluation . Free Talk teens reported higher quality and satisfaction ratings , and MI integrity scores were higher for Free Talk groups . AOD use and delinquency decreased for both groups at 3 months , and 12-month recidivism rates were lower but not significantly different for the Free Talk group compared to UC . Results contribute to emerging literature on MI in a group setting . A longer term follow-up is warranted BACKGROUND Brief motivational intervention ( BMI ) has shown promising results to reduce alcohol use in young adults . Knowledge on mechanisms that predict BMI efficacy could potentially improve treatment effect sizes through data that optimize clinical training and implementation . Particularly , little attention has been given to counselor influence on treatment mechanisms . METHODS We investigated the influence of counselors on BMI efficacy in reducing alcohol use among non-treatment-seeking young men ( age 20 ) screened as hazardous drinkers . Participants were r and omly allocated to ( i ) a group receiving a single BMI from 1 of 18 counselors selected to maximize differences in several of their characteristics ( gender , professional status , clinical experience , and motivational interviewing [ MI ] experience ) or ( ii ) a control group receiving assessment only . Drinking at 3-month follow-up was first compared between the BMI and control groups to assess efficacy . Then , the influence of counselors ' characteristics ( i.e. , gender , professional status , clinical experience , MI experience , BMI attitudes , and expectancies ) and within-session behaviors ( i.e. , measured by the Motivational Interviewing Skill Code ) on outcome was tested in regression analyses . RESULTS There was a significant ( p = 0.02 ) decrease in alcohol use among the BMI group compared to the control group . Counselors that were male , more experienced , that had more favorable BMI attitudes and expectancies , higher MI skills , but surprisingly less MI-consistent behaviors , had significantly better outcomes than the control group while their counterparts did not . CONCLUSIONS The current study demonstrated BMI efficacy on alcohol use reduction within a sample of non-treatment-seeking young adult males . Moreover , BMI effect was related to interindividual differences among counselors , and results therefore provide recommendations for BMI training and implementation with similar population OBJECTIVES Adolescents in their late teens and early 20s have the highest alcohol consumption in the United States ; binge drinking peaks at age 21 - 25 years . Underage drinking is associated with many negative consequences , including academic problems and risk of intentional and unintentional injuries . This study tested the effectiveness of pediatric emergency department ( PED ) screening and brief intervention to reduce alcohol consumption and associated risks . METHODS A three-group r and omized assignment trial was structured to test differences between intervention ( I ) and st and ard assessed control ( AC ) groups in alcohol consumption and alcohol-related behaviors from baseline to 12 months and to compare the AC group with a minimally assessed control ( MAC ) group to adjust for the effect of assessment reactivity on control group behavior . Patients aged 14 - 21 years were eligible if they screened positive on the Alcohol Use Disorders Identification Test ( AUDIT ) or for binge drinking or high-risk behaviors . The MAC group received a re source h and out , written advice about alcohol-related risks , and a 12-month follow-up appointment . Patients in the AC group were assessed using st and ardized instruments in addition to the MAC protocol . The I group received a peer-conducted motivational intervention , referral to community re sources and treatment if indicated , and a 10-day booster in addition to assessment . Measurements included 30-day self-report of alcohol consumption and alcohol-related behaviors , screens for depression and posttraumatic stress disorder , and self-report of attempts to quit , cut back , or change conditions of use , all repeated at follow-up . Motor vehicle records and medical records were also analyzed for changes from baseline to 1-year follow-up . RESULTS Among 7,807 PED patients screened , 1,202 were eligible ; 853 enrolled ( I , n = 283 ; AC , n = 284 ; MAC , n = 286 ) , with a 12-month follow-up rate of 72 % . At 12 months , more than half of enrollees in Reaching Adolescents for Prevention ( RAP ) attempted to cut back on drinking , and over a third tried to quit . A significantly larger proportion of the I group made efforts to quit drinking and to be careful about situations when drinking compared to AC enrollees , and there was a numerically but not significantly greater likelihood ( p = 0.065 ) among the I group for efforts to cut back on drinking . At 3 months , the likelihood of the I group making attempts to cut back was almost triple that of ACs . For efforts to quit , it was double , and for trying to be careful about situations when drinking , there was a 72 % increase in the odds ratio ( OR ) for the I group . Three-month results for attempts were sustained at 12 months for quit attempts and efforts to be careful . Consumption declined in both groups from baseline to 3 months to 12 months , but there were no significant between-group differences in alcohol-related consequences at 12 months or in alcohol-related risk behaviors . We found a pattern suggestive of assessment reactivity in only one variable at 12 months : the attempt to cut back ( 73.3 % for the I group vs. 64.9 % among the AC group and 54.8 % among the MAC group ) . CONCLUSIONS Brief motivational intervention result ed in significant efforts to change behavior ( quit drinking and be careful about situations while drinking ) but did not alter between-group consumption or consequences By the age of 18 , between 16 and 27 % of adolescents in the U.S. have been arrested for an offense and by the age of 23 this increases to a staggering 25 - 41 % . Most youth that get into legal trouble have a substance abuse problem and many youth report high risk driving behaviors . Adjudication of adolescents for an offense may provide an opportunity to provide a secondary prevention program for such high risk behaviors . In this regard the primary aim of the present study was to test two hypotheses : ( 1 ) that interventions involving group motivational interviewing would decrease future legal charges beyond those achieved by the combination of sanctions and remedial actions otherwise m and ated by the court ; and ( 2 ) that the addition of a trauma room exposure to the group MI intervention would increase the effectiveness of MI in decreasing these future legal charges . Court m and ated youth who have had a high risk driving police charge and /or alcohol related police charge and who are drivers ( n=992 ) were r and omly assigned to one of the three 20h interventions ; enhanced prototypic community service ( CS ) , Motivational Intervention with typical community service ( MI ) , and Motivational Intervention with exposure to a hospital trauma center ( MI-H ) . As hypothesized , the probability of being charged with an offense within the 6 months post-treatment was significantly less for participants in the combined MI groups than those in the CS group . The combined MI groups also had significantly fewer overall number of police charge events than the CS group at 6 months . Mediation analyses revealed that the relationship between MI vs. CS interventions and subsequent police charges was partially accounted for by the youth 's experience of the MI component of the intervention . Despite fewer police charges at 6 months the combined MI group reported ( 1 ) significantly more hazardous drinking and ( 2 ) a greater amount of speeding and distracted driving than the control group over this same 6-month period . Hypothesis 2 , that MI-H would be more effective than MI in reducing police charges , was not supported . This was so despite evidence supporting the hypotheses that ( 1 ) trauma room exposure would increase participants ' emotional arousal during the intervention and ( 2 ) increased arousal would be predictive of fewer police charges . Despite support for the theorized causal pathway , the combination of trauma room exposure and MI did not result in better outcomes than MI combined with traditional community service . Given this discrepancy between empirical supports for the theory in the face of the absence of incremental effectiveness of the MI-H treatment condition , a better underst and ing of the participant 's hospital experience will be necessary if we are to successfully utilize the trauma room exposure to increase the effectiveness of MI interventions for this target group to achieve better outcomes BACKGROUND Questions remain about how brief motivational interventions ( BMI s ) for unhealthy alcohol use work , and addressing these questions may be important for improving their efficacy . Therefore , we assessed the effects of various characteristics of BMI s on drinking outcomes across 3 r and omized controlled trials ( RCTs ) . METHODS Audio recordings of 314 BMI s were coded . We used the global rating scales of the Motivational Interviewing Skills Code ( MISC ) 2.1 : counselor 's acceptance , empathy , and motivational interviewing ( MI ) spirit , and patient 's self-exploration were rated . MI proficiency was defined as counselor 's rating scale scores ≥5 . We also used the structure , confrontation , and advice subscale scores of the Therapy Process Rating Scale and the Working Alliance Inventory . We examined these process characteristics in interventions across 1 U.S. RCT of middle-aged medical in patients with unhealthy alcohol use ( n = 124 ) and 2 Swiss RCTs of young men with binge drinking in a non clinical setting : Swiss-one ( n = 62 ) and Swiss-two ( n = 128 ) . We assessed the associations between these characteristics and drinks/d reported by participants 3 to 6 months after study entry . RESULTS In all 3 RCTs , mean MISC counselor 's rating scales scores were consistent with MI proficiency . In overdispersed Poisson regression models , most BMI characteristics were not significantly associated with drinks/d in follow-up . In the U.S. RCT , confrontation and self-exploration were associated with more drinking . Giving advice was significantly associated with less drinking in the Swiss-one RCT . Contrary to expectations , MI spirit was not consistently associated with drinking across studies . CONCLUSIONS Across different population s and setting s , intervention characteristics viewed as central to efficacious BMI s were neither robust nor consistent predictors of drinking outcome . Although there may be alternative reasons why the level of MI processes was not predictive of outcomes in these studies ( limited variability in scores ) , efforts to underst and what makes BMI s efficacious may require attention to factors beyond intervention process characteristics typically examined 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 OBJECTIVE To determine whether a brief individual motivational interview ( IMI ) plus a family motivational interview ( Family Check-Up [ FCU ] ) would reduce alcohol use in adolescents treated in an emergency department after an alcohol-related event more effectively than would an IMI only . DESIGN Two-group r and omized design with 3 follow-up time points . SETTING An urban regional level I trauma center . PARTICIPANTS Adolescents aged 13 to 17 years ( N = 125 ) with a positive blood alcohol concentration as tested using blood , breath , or saliva . INTERVENTIONS Either IMI or IMI plus FCU . MAIN OUTCOME MEASURES Drinking frequency ( days per month ) , quantity ( drinks per occasion ) , and frequency of high-volume drinking ( ≥5 drinks per occasion ) . RESULTS Both conditions result ed in a reduction in all drinking outcomes at all follow-up points ( P < .001 for all ) , with the strongest effects at 3 and 6 months . Adding the FCU to the IMI result ed in a somewhat better outcome than did the IMI only on high-volume drinking days at 3-month follow-up ( 14.6 % vs 32.1 % , P = .048 ; odds ratio , 2.76 ; 95 % confidence interval , 0.99 - 7.75 ) . CONCLUSIONS Motivational interventions have a positive effect on drinking outcomes in the short term after an alcohol-related emergency department visit . Adding the FCU to an IMI result ed in somewhat better effects on high-volume drinking at short-term follow-up than did an IMI only . The cost of extra sessions necessary to complete the FCU should be weighed against the potential benefit of reducing high-volume drinking when considering adding the FCU to an IMI for this population OBJECTIVE Motivational interviewing to reduce alcohol and marijuana use among incarcerated adolescents was evaluated . METHOD Adolescents ( N = 162 , 84 % male ; M = 17.10 years old ) were r and omly assigned to receive motivational interviewing or relaxation training , with follow-up assessment 3 months after release . RESULTS Compared with those who received relaxation training , adolescents who received motivational interviewing had lower rates of alcohol and marijuana use at follow-up , with some evidence for moderating effects of depression . At low levels of depression , adolescents who received motivational interviewing had lower rates of use . Adolescents who received relaxation training and who had high levels of depressive symptoms early in incarceration showed less use at follow-up than those low in depressive symptoms who received relaxation training . CONCLUSIONS This brief motivational interviewing intervention during incarceration reduces alcohol and marijuana use after release . In addition , depressive symptoms early in incarceration should be considered in treating these adolescents , but more work is needed to extend follow-up period and account for the impact of depression on outcomes Motivational interviewing ( MI ) is a brief intervention that has been shown to reduce heavy drinking among college students . Because all college studies of MI to date have included a personalized feedback report , it remains unclear which of the components is necessary to produce behavior change . This study evaluated the separate and collective effects of MI and feedback among 122 “ binge ” drinking college students . Participants were r and omized to : 1 ) MI with feedback , 2 ) MI without feedback , 3 ) Mailed feedback only , 4 ) MI with mailed feedback , or 5 ) Assessment only control . At an eight-week follow-up , all groups reduced their consumption , peak BAC , consequences , and dependence symptoms . For females , there were reductions in consequences and dependence symptoms in groups that received feedback , as compared to groups that did not receive feedback . For females , there was an effect of the feedback on consequences and dependence symptoms , but was no overall effect of MI on any outcome measure BACKGROUND AND OBJECTIVES : Emergency department ( ED ) visits present an opportunity to deliver brief interventions ( BIs ) to reduce violence and alcohol misuse among urban adolescents at risk for future injury . Previous analyses demonstrated that a BI result ed in reductions in violence and alcohol consequences up to 6 months . This article describes findings examining the efficacy of BIs on peer violence and alcohol misuse at 12 months . METHODS : Patients ( 14–18 years of age ) at an ED reporting past year alcohol use and aggression were enrolled in the r and omized control trial , which included computerized assessment , r and om assignment to control group or BI delivered by a computer or therapist assisted by a computer . The main outcome measures ( at baseline and 12 months ) included violence ( peer aggression , peer victimization , violence-related consequences ) and alcohol ( alcohol misuse , binge drinking , alcohol-related consequences ) . RESULTS : A total of 3338 adolescents were screened ( 88 % participation ) . Of those , 726 screened positive for violence and alcohol use and were r and omly selected ; 84 % completed 12-month follow-up . In comparison with the control group , the therapist assisted by a computer group showed significant reductions in peer aggression ( P < .01 ) and peer victimization ( P < .05 ) at 12 months . BI and control groups did not differ on alcohol-related variables at 12 months . CONCLUSIONS : Evaluation of the SafERteens intervention 1 year after an ED visit provides support for the efficacy of computer-assisted therapist brief intervention for reducing peer violence This study evaluated the efficacy of two brief personalized feedback interventions ( PFIs ) using identical feedback and motivational interviewing strategies aim ed at reducing alcohol consumption and alcohol-related problems to two control conditions among a sample of high-risk drinking college students . Students ( N = 152 ) were r and omly assigned to a computer-delivered PFI with a video interviewer , a face-to-face PFI with a live interviewer , a comprehensive assessment condition , or a minimal assessment -only condition . At 10 weeks posttreatment , the face-to-face PFI significantly reduced weekly drinking quantity and peak and typical blood alcohol concentration compared with the comprehensive assessment and minimal assessment -only conditions ( d values ranged from 0.32 to 0.61 ) . No significant between-group differences were evidence d for the computer-delivered PFI condition , although effect sizes were comparable to other college drinking studies using computer-delivered interventions ( d values ranged from 0.20 to 0.27 ) . Results provide further support for the use of a face-to-face PFI to help reduce college students ' alcohol consumption and suggest that a video interviewer in the context of a computer-delivered PFI is likely a helpful but not necessarily a complete substitute for a live interviewer Motivational interviewing ( MI ) is an effective treatment for substance use disorders ( SUDs ) that focuses on resolving ambivalence and increasing commitment to positive behavior change . Although MI has a well-developed clinical theory , research findings have been mixed in supporting its view of how change occurs . The primary aim of this pilot study was to test hypothesized MI active ingredients and mechanisms of change in reducing drinking during the initiation of a behavior change episode . Problem drinkers ( N = 89 ) seeking treatment were r and omly assigned to MI , relational MI without directive elements ( spirit-only MI [ SOMI ] ) , or a self-change ( SC ) control condition . Participants were followed during an 8-week treatment period . The first 2 of 4 treatment sessions were videotaped and coded for fidelity , discriminability , and change talk . Overall , conditions demonstrated high fidelity . As predicted , change talk significantly increased in MI relative to the SOMI condition . Drinking was significantly reduced at end treatment , but the reduction was equivalent across conditions . Post hoc analyses found that MI reduced drinking more rapidly than SOMI and SC and that increased change talk mediated the effects of MI relative to SOMI during the week immediately following the first session . Findings are discussed in the context of the pilot nature of the study and the relative absence of experimental tests of mechanisms of behavior change in SUD treatment research to test early nutritional interventions and prospect i ve observational cohorts . RCTs are generally accepted as method ologically the best approach for informing health policy . They can equalise unknown as well as known confounding factors and so can demonstrate causation ; they permit estimation of effect size and so can be used to assess likely In this study , the authors evaluated the efficacy of a brief motivational intervention ( BMI ) and a computerized program for reducing drinking and related problems among college students sanctioned for alcohol violations . Referred students ( N = 198 , 46 % women ) , stratified by gender , were r and omly assigned to a BMI or to the Alcohol 101 Plus computer program . Data obtained at baseline , 1 , 6 , and 12 months were used to evaluate intervention efficacy . Planned analyses revealed 3 primary findings . First , women who received the BMI reduced drinking more than did women who received the computer intervention ; in contrast , men 's drinking reductions did not differ by condition . Second , readiness to change and hazardous drinking status predicted drinking reductions at 1 month postintervention , regardless of intervention . Third , by 1 year , drinking returned to presanction ( baseline ) levels , with no differences in recidivism between groups . Exploratory analyses revealed an overall mean reduction in drinking immediately after the sanction event and before taking part in an intervention . Furthermore , after the self-initiated reductions prompted by the sanction were accounted for , participation in the BMI but not the computer intervention was found to produce additional reduction in drinking and related consequences OBJECTIVE The current study examined the efficacy of mailed personalized normative feedback ( PNF ) as a brief alcohol intervention for at-risk college drinkers , and investigated discrepancy as a possible mediator of the intervention effect . METHOD Participants consisted of 100 at-risk college drinkers who completed an alcohol-use assessment at baseline , 6-week posttest and 6-month follow-up . Measures included number of drinks consumed per heaviest drinking week , frequency of heavy-drinking episodes , peak blood alcohol concentration and number of alcohol-related problems , all for the last month . Participants were r and omly assigned to either a mailed brief intervention ( MBI ; n = 49 ) or attention-control ( C ; n = 51 ) group . The MBI group received mailed PNF that was based on baseline responses to the drinking measures ; the C group received a psychoeducational brochure about alcohol . RESULTS Mixed-model , repeated measures ANOVAs were used to examine the effects of time , group and gender on discrepancy and the drinking variables . Following the intervention , the MBI group reported significantly higher perceived discrepancy between self and others ' drinking than the C group . The MBI group reported consuming significantly fewer drinks per heaviest drinking week and engaging in heavy episodic drinking less frequently than the C group at the 6-week posttest ; however , these differences were no longer evident at the 6-month follow-up . Hierarchical regression analyses did not provide evidence for the hypothesized mediating effect of discrepancy . CONCLUSIONS Mailed PNF may be a cost- and time-efficient means of developing discrepancy and temporarily reducing heavy alcohol consumption among at-risk college drinkers BACKGROUND The prevention of initiation of tobacco , alcohol and drug use is a major societal challenge , for which the existing research literature is generally disappointing . This study aim ed to test the effectiveness of adaptation of Motivational Interviewing ( MI ) for universal prevention purpose s , i.e. to prevent initiation of new substance use among non-users , and to reduce risks among existing users . METHODS Cluster r and omised trial with 416 students aged 16 - 19 years old recruited in 12 London Further Education colleges without regard to substance use status . Individualised MI was compared with st and ard practice classroom-delivered Drug Awareness intervention , both delivered over the course of one lesson . Prevalence , initiation and cessation rates for the 3 target behaviours of cigarette smoking , alcohol consumption and cannabis use , along with reductions in use and harm indicators after both 3 and 12 months were assessed . RESULTS This adaptation of MI was not demonstrated to be effective in either intention-to-treat or sub-group analyses for any outcome . Unexpected lower levels of cannabis initiation and prevalence were found in the Drug Awareness control condition . CONCLUSIONS This particular adaptation of MI is ineffective as a universal drug prevention intervention and does not merit further study 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 Many college women are at risk for pregnancy , and binge drinking college women are often at risk for alcohol-exposed pregnancy . Brief interventions with sustainable outcomes are needed , particularly for college women who are binge drinking , at risk for pregnancy , and at increased risk of alcohol-exposed pregnancy . Two-hundred-twenty-eight women at a Mid-Atlantic urban university at risk for alcohol-exposed pregnancy enrolled in the r and omized clinical trial , and 207 completed the 4 month follow-up . The BALANCE intervention used Motivational Interviewing plus feedback to target drinking and contraception behaviors . Main outcome measures included ( 1 ) the rate of risk for alcohol-exposed pregnancy , ( 2 ) the rate of risk drinking , and ( 3 ) the rate of pregnancy risk . At 4-month follow-up , the rate of alcohol-exposed pregnancy risk was significantly lower in the intervention ( 20.2 % ) than the control condition ( 34.9 % ) , ( P < .02 ) . Assignment to the intervention condition halved the odds of women remaining at risk for alcohol-exposed pregnancy , while not receiving the intervention doubled the odds of continued alcohol-exposed pregnancy risk ( OR = 2.18 ; 95 % CI = 1.16–4.09 ) . A baseline history of blackouts , continued high blood alcohol drinking days at 1 month , and continued risk for pregnancy at 1 month independently contributed to a multivariate model of continued alcohol-exposed pregnancy risk at 4 month follow-up . BALANCE reduced alcohol-exposed pregnancy risk , with similar outcomes to longer interventions . Because early response predicted sustained alcohol-exposed pregnancy risk reduction , those who fail to achieve initial change could be identified for further intervention . The BALANCE intervention could be adopted into existing student health or university alcohol programs . The risks of unintended pregnancy and alcohol-exposed pregnancy among binge drinking women in college merit greater prevention efforts BACKGROUND Heavy drinking is one of the leading causes of morbidity and mortality in young men . Brief motivational intervention ( BMI ) has shown promising results for young people , but has never been tested in young men in the community who volunteered to receive an intervention . METHODS We evaluated the effectiveness of BMI in reducing alcohol use among heavy episodic users and in maintaining low-risk drinking among nonheavy episodic users . Participants were French-speaking young men attending the m and atory Swiss army conscription process . They were offered the opportunity to receive a 20-minute BMI , and those interested were r and omized into an intervention group ( BMI immediately ) or into a control group ( BMI after the 6-month follow-up assessment , in a waiting list design ) . Analyses were conducted separately for heavy and nonheavy episodic users ( separated using baseline heavy episodic use frequency ) as the hypotheses tested were different between both groups ( primary vs. secondary prevention intervention ) . RESULTS From a pool of 6,085 young men invited to receive BMI , 727 ( 11.9 % ) showed up and 572 were included in the study ( after exclusions related to organizational aspects of the conscription process ) . Among nonheavy episodic users , there was a protective effect of BMI on weekly alcohol use ( p < 0.05 ) . Among heavy episodic users , there were no significant effects of BMI . CONCLUSIONS About 12 % of young men were interested in addressing their drinking within the BMI framework , suggesting that there is some need for easily accessible alcohol intervention . The present intervention did have a preventive effect among low-risk young drinkers in helping them maintain their patterns of alcohol use . An explanation for the lack of effectiveness among heavy episodic users might be that those individuals interested in BMI had patterns of more severe alcohol use , thereby making change more difficult Two brief treatments for problem gambling were compared with a waiting-list control in a r and omized trial . Eighty-four percent of participants ( N = 102 ) reported a significant reduction in gambling over a 12-month follow-up period . Participants who received a motivational enhancement telephone intervention and a self-help workbook in the mail , but not those who received the workbook only , had better outcomes than participants in a 1-month waiting-list control . Participants who received the motivational interview and workbook showed better outcomes than those receiving the workbook only at 3- and 6-month follow-ups . At the 12-month follow-up , the advantage of the motivational interview and workbook condition was found only for participants with less severe gambling problems . Overall , these results support the effectiveness of a brief telephone and mail-based treatment for problem gambling 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 OBJECTIVE This study evaluated the costs and cost-effectiveness of combining motivational interviewing with feedback to address heavy drinking among university freshmen . METHOD Microcosting methods were used in a prospect i ve cost and cost-effectiveness study of a r and omized trial of assessment only ( AO ) , motivational interviewing ( MI ) , feedback only ( FB ) , and motivational interviewing with feedback ( MIFB ) at a large public university in the southeastern United States . Students were recruited and screened into the study during freshman classes based on recent heavy drinking . A total of 727 students ( 60 % female ) were r and omized , and 656 had sufficient data at 3-months ' follow-up to be included in the cost-effectiveness analysis . Effectiveness outcomes were changes in average drinks per drinking occasion and number of heavy drinking occasions . RESULTS Mean intervention costs per student were $ 16.51 for MI , $ 17.33 for FB , and $ 36.03 for MIFB . Cost-effectiveness analysis showed two cost-effective interventions for both outcomes : AO ( $ 0 per student ) and MIFB ( $ 36 per student ) . CONCLUSIONS This is the first prospect i ve cost-effectiveness study to our knowledge to examine MI for heavy drinking among students in a university setting . Despite being the most expensive intervention , MIFB was the most effective intervention and may be a cost-effective intervention , depending on a university 's willingness to pay for changes in the considered outcomes This study evaluated the efficacy of two brief personalized normative feedback interventions aim ed at reducing heavy drinking among m and ated college students ( N = 135 ) . Students were r and omly assigned to one of two conditions : Web-based assessment with self-guided personalized normative feedback ( SWF ) or Web-based assessment with counselor-guided personalized normative feedback ( CWF ) . Results indicated that students in the CWF condition reported significantly greater reductions in weekly drinking quantity and binge drinking frequency than those in the SWF group at follow-up ( M = 8 months ) . Students in the CWF group also reported significantly greater reductions in estimates of peer drinking from baseline to the follow-up assessment than students in the SWF group . In addition , changes in estimates of peer drinking partially mediated the effect of the intervention on changes in drinking . Results suggest that counselor-guided feedback may be more effective in reducing drinking among m and ated students relative to self-guided feedback in the long term This study examined the effectiveness of a single-session group motivational enhancement alcohol intervention on adjudicated male college students . Over two sequential academic years , 230 students sanctioned by the university for alcohol-related infractions attended a 60- to 75-minute group intervention . The intervention consisted of a timeline followback , social norms education , decisional balance for behavioral change , blood alcohol content ( BAC ) information , expectancy challenge , and generation of behavioral goals . Participants were followed weekly for three months and showed reductions in drinking ( 29 % ) and alcohol-related consequences ( 32 % ) at three-month follow-up . The intervention was successful in reducing drinking for both first-year students and upperclassmen , with reductions appearing to be a function of the intervention and not the citation itself . Furthermore , a post hoc control condition revealed that those participants r and omly assigned to the intervention group condition reduced drinking ( 19 % ) and alcohol-related consequences ( 44 % ) more than participants in the control condition over one month . These results provide continued evidence of the effectiveness of group motivational enhancement interventions with adjudicated male college students OBJECTIVE Female college students have increased their alcohol consumption rates . The current study sought to replicate the effectiveness of a female-specific motivational-enhancement group intervention and extended previous work by adding a 6-month follow-up . The intervention included several motivational-enhancement components delivered in a group setting and included a group discussion of female-specific reasons for drinking . METHOD Participants were 285 first-year college women . Data collection consisted of an online pre-intervention question naire , 10 weeks of online follow-up assessment , and a 6-month online follow-up . Using a r and omized design , participants chose a group session , blind to treatment status . Held during the first weeks of the first semester , 159 participants received the intervention and 126 participants received an assessment -only control . RESULTS Using a repeated- measures analysis of covariance , intervention participants consumed significantly less than control participants on drinks per week ( F = 11.86 , 1/252 df , p < .001 ) , maximum drinks ( F = 11.90 , 1/252 df , p < .001 ) , and heavy episodic drinking events ( F = 20.14 , 1/252 df , p < .001 ) across 10 weeks of follow-up . However , these effects did not persist at the 6-month follow-up . Moderation effects were found for social motives on all drinking variables , such that the intervention was most effective for those women with higher social motives for drinking . CONCLUSIONS Efficacy was found for a female-specific motivational group intervention in creating less risky drinking patterns among first-year women , especially women with social motives for drinking . The effect dissipated by the second semester , suggesting the need for maintenance or booster sessions OBJECTIVE This study tested the effectiveness of brief primary care provider interventions delivered in a college student health center to a sample of college students who screened positive for high-risk drinking . METHOD Between November 2005 and August 2006 , 8,753 students who presented as new patients to the health service at a large public university were screened for high-risk drinking , and 2,484 students ( 28 % ) screened positive on the 5/4 gender-specific high-risk drinking question ( i.e. , five or more drinks per occasion for men and four or more for women ) . Students who screened positive for high-risk drinking and consented to participate ( N= 363 ; 52 % female ) were r and omly assigned either to a control group ( n = 182 ) or to an experimental group ( n = 181 ) . Participants in the experimental group received two brief intervention sessions that were founded in motivational interviewing techniques and delivered by four specially trained providers within the student health center . Data on alcohol use and related harms were obtained from a Web-based Healthy Lifestyle Question naire , 30-day Timeline Followback alcohol-use diaries , the Rutgers Alcohol Problem Index ( RAPI ) , and eight items from the Drinker Inventory of Consequences-2L . RESULTS Repeated measures analysis showed that , compared with the control group ( C ) , the intervention group ( I ) had significant reductions in typical estimated blood alcohol concentration ( BAC ) ( C = .071 vs I = .057 at 3 months ; C = .073 vs I = .057 at 6 months ) , peak BAC ( C = . 142 vs I = .112 at 3 months ; C = .145 vs I = .108 at 6 months ) , peak number of drinks per sitting ( C = 8.03 vs I = 6.87 at 3 months ; C = 7.98 vs I = 6.52 at 6 months ) , average number of drinks per week ( C = 9.47 vs I = 7.33 at 3 months ; C = 8.90 vs I = 6.16 at 6 months ) , number of drunk episodes in a typical week ( C = 1.24 vs I = 0.85 at 3 months ; C = 1.10 vs I = 0.71 at 6 months ) , number of times taken foolish risks ( C = 2.24 vs I = 1.12 at 3 months ) , and RAPI sum scores ( C = 6.55 vs I = 4.96 at 6 months ; C = 6.17 vs I = 4.58 at 9 months ) . CONCLUSIONS Brief interventions delivered by primary care providers in a student health center to high-risk-drinking students may result in significantly decreased alcohol consumption , high-risk drinking , and alcohol-related harms OBJECTIVE To examine the maintenance of effects of Motivational Enhancement Therapy ( MET ) shown to improve risk behaviors and viral load in youth living with HIV ( YLH ) immediately posttreatment . METHODS Sixty-five youth ( ages 16 - 25 years ) were r and omized to Healthy Choices or a waitlist control . Frequency of substance use , frequency of unprotected intercourse , and viral load were obtained at baseline , 3 , and 6 months after study entry . The waitlist control then received intervention . An additional data collection was obtained at 9 months for follow-up of the original treatment group . RESULTS One-tailed ANOVA showed that the treatment group had greater reductions in viral load and alcohol use from baseline to 6 months . These reductions appeared to be maintained at 9-month follow-up . Improvements in sexual risk were not evident . CONCLUSIONS MET showed significant promise in reducing substance use and in improving HIV-related health in YLH immediately posttreatment . These effects were maintained after treatment termination Alcohol consumption among college students has become an increasing problem that requires attention from college administrators , staff , and research ers . Despite the physiological differences between men and women , college women are drinking at increasingly risky rates , placing them at increased risk for negative consequences . The current study tested a group motivational enhancement approach to the prevention of heavy drinking among 1st-year college women . Using a r and omized design , the authors assigned participants either to a group that received a single-session motivational enhancement intervention to reduce risky drinking that focused partly on women 's specific reasons for drinking ( n = 126 ) or to an assessment -only control group ( n = 94 ) . Results indicated that , relative to the control group participants , intervention participants drank fewer drinks per week , drank fewer drinks at peak consumption events , and had fewer alcohol-related consequences over a 10-week follow-up . Further , the intervention , which targeted women 's reasons for drinking , was more effective in reducing consumption for participants with high social and enhancement motivations for drinking The authors evaluated the efficacy of Brief Alcohol Screening and Intervention for College Students ( BASICS - L. A. Dimeff , J. S. Baer , D. R. Kivlahan , & G. A. Marlatt , 1999 ) , a single session of drinking-related feedback intended to reduce heavy drinking and related harm . College student drinkers ( N = 99 ) were assigned to BASICS , an educational intervention , or an assessment -only control group . At 3 months postintervention . there were no overall significant group differences , but heavier drinking BASICS participants showed greater reductions in weekly alcohol consumption and binge drinking than did heavier drinking control and education participants . At 9 months , heavier drinking BASICS participants again showed the largest effect sizes . BASICS participants evaluated the intervention more favorably than did education participants . This study suggests that BASICS may be more efficacious than educational interventions for heavier drinking college students Criminally involved adolescents engage in high levels of risky sexual behavior and alcohol use , and alcohol use may contribute to lack of condom use . Detained adolescents ( n = 484 ) were r and omized to ( 1 ) a theory-based sexual risk reduction intervention ( GPI ) , ( 2 ) the GPI condition with a group-based alcohol risk reduction motivational enhancement therapy component ( GPI + GMET ) , or ( 3 ) an information-only control ( INFO ) . All interventions were presented in same-sex groups in single sessions lasting from 2 to 4 hr . Changes to putative theoretical mediators ( attitudes , perceived norms , self-efficacy , and intentions ) were measured immediately following intervention administration . The primary outcomes were risky sexual behavior and sexual behavior while drinking measured 3 months later ( 65.1 % retention ) . The GPI + GMET intervention demonstrated superiority over both other conditions in influencing theoretical mediators and over the INFO control in reducing risky sexual behavior . Self-efficacy and intentions were significant mediators between condition and later risky sexual behavior . This study contributes to an underst and ing of harm reduction among high-risk adolescents and has implication s for underst and ing circumstances in which the inclusion of GMET components may be effective OBJECTIVES This paper presents up to 5 years post-program outcomes of Project Towards No Drug Abuse ( Project TND ) , a drug abuse prevention program conducted in South California alternative high school system during years 1994 - 1999 . METHODS The effects of a 9-session health motivation -- social skills -- decision-making curriculum were evaluated . Twenty-one schools recruited were r and omly assigned to st and ard care ( control ) , classroom only , or a classroom plus semester-long school-as-community component . Last 30-day use of cigarettes , alcohol , marijuana , and hard drugs were assessed at three time intervals : short-term ( year 1 ) , middle-term ( years 2 or 3 ) , and long-term ( years 4 or 5 ) . Multilevel r and om coefficients modeling were employed to estimate the adjusted levels of substance use . RESULTS Among 1578 baseline subjects , follow-up data were available for 68 % ( year 1 ) , 66 % ( years 2 or 3 ) , and 46 % ( years 4 or 5 ) of subjects , respectively . Results revealed significant positive long-term program effects for hard drug use at year 4 or 5 for the two program interventions ( P = 0.02 ) . CONCLUSIONS Project TND reduced hard drug use in the 46 % who were successfully followed . It is the first program to demonstrate long-term self-reported behavioral effects on hard drug use among high-risk youth by using a school-based , limited-session model OBJECTIVE To evaluate moderators and mediators of brief alcohol interventions conducted in the emergency department . METHODS Patients ( 18 - 24 years ; n = 172 ) in an emergency department received a motivational interview with personalized feedback ( MI ) or feedback only ( FO ) , with 1- and 3-month booster sessions and 6- and 12-month follow-ups . Gender , alcohol status/severity group [ ALC+ only , Alcohol Use Disorders Identification Test ( AUDIT+ ) only , ALC+/AUDIT+ ] , attribution of alcohol in the medical event , aversiveness of the event , perceived seriousness of the event and baseline readiness to change alcohol use were evaluated as moderators of intervention efficacy . Readiness to change also was evaluated as a mediator of intervention efficacy , as were perceived risks/ benefits of alcohol use , self-efficacy and alcohol treatment seeking . RESULTS Alcohol status , attribution and readiness moderated intervention effects such that patients who had not been drinking prior to their medical event , those who had low or medium attribution for alcohol in the event and those who had low or medium readiness to change showed lower alcohol use 12 months after receiving MI compared to FO . In the AUDIT+ only group those who received MI showed lower rates of alcohol-related injury at follow-up than those who received FO . Patients who had been drinking prior to their precipitating event did not show different outcomes in the two interventions , regardless of AUDIT status . Gender did not moderate intervention efficacy and no significant mediation was found . CONCLUSIONS Findings may help practitioners target patients for whom brief interventions will be most effective . More research is needed to underst and how brief interventions transmit their effects 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 This study tested two forms of alcohol reduction programming for college students . Thirty-seven moderate to heavy drinkers completed measures of quantity/frequency , drinking consequences , and attitude question naires . Participants were r and omly assigned to one of three groups : 1 ) a two-hour information and motivation session plus mailed personal feedback on their drinking ; 2 ) mailed feedback only ; or 3 ) no treatment . At a 6-week follow-up session , the feedback-only group decreased drinks per month as compared to control . No other differences were statistically significant , though decreases favored the treatment conditions about equally over control . Implication s for research and treatment are discussed 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 OBJECTIVE The aim of this study was to evaluate a brief motivational intervention ( BMI ) for reducing risky alcohol use and alcohol-related problems among m and ated ( M ) and voluntary ( V ) student drinkers to determine ( a ) whether BMI -m and ated students report greater decreases in alcohol use and related problems , relative to no treatment ; ( b ) whether a BMI is comparably effective for m and ated and voluntary students ; and ( c ) whether a m and ated control group shows greater changes in alcohol use and related problems relative to a voluntary control group . METHOD Participants were undergraduate student research volunteers ( 62 % male ) who met heavy drinking criteria and completed measures of alcohol use and alcohol problems at baseline and 4 weeks after intervention . Participants ( N = 84 ) were r and omly assigned to treatment ( T ) or assessment -only control ( C ) conditions ( m and ated students were assigned to a brief wait list ) . RESULTS Participants assigned to treatment reported consuming fewer drinks after the intervention ( MT : M = 14.11 drinks ; VT : M = 14.05 ) relative to control groups ( MC : M = 20.71 ; VC : M = 16.53 ) . Evaluation of alcohol-related problems indicated a significant effect of referral status , such that m and ated students reported significantly fewer problems at the follow-up assessment relative to volunteers . CONCLUSIONS BMI s are comparably effective for m and ated and voluntary students and may result in larger reductions in alcohol use than disciplinary attention alone . More longitudinal research is needed to evaluate the long-term impact of a BMI among m and ated students BACKGROUND There is compelling evidence supporting screening and brief intervention ( SBI ) for hazardous drinking , yet it remains underused in primary health care . Electronic ( computer or Web-based ) SBI ( e-SBI ) offers the prospect s of ease and economy of access . We sought to determine whether e-SBI reduces hazardous drinking . METHODS We conducted a r and omized controlled trial in a university primary health care service . Participants were 975 students ( age range , 17 - 29 years ) screened using the Alcohol Use Disorders Identification Test ( AUDIT ) . Of 599 students who scored in the hazardous or harmful range , 576 ( 300 of whom were women ) consented to the trial and were r and omized to receive an information pamphlet ( control group ) , a Web-based motivational intervention ( single-dose e-SBI group ) , or a Web-based motivational intervention with further interventions 1 and 6 months later ( multidose e-SBI group ) . RESULTS Relative to the control group , the single-dose e-SBI group at 6 months reported a lower frequency of drinking ( rate ratio [ RR ] , 0.79 ; 95 % confidence interval [ CI ] , 0.68 - 0.94 ) , less total consumption ( RR , 0.77 ; 95 % CI , 0.63 - 0.95 ) , and fewer academic problems ( RR , 0.76 ; 95 % CI , 0.64 - 0.91 ) . At 12 months , statistically significant differences in total consumption ( RR , 0.77 ; 95 % CI , 0.63 - 0.95 [ equivalent to 3.5 st and ard drinks per week ] ) and in academic problems ( RR , 0.80 ; 95 % CI , 0.66 - 0.97 ) remained , and the AUDIT scores were 2.17 ( 95 % CI , -1.10 to -3.24 ) points lower . Relative to the control group , the multidose e-SBI group at 6 months reported a lower frequency of drinking ( RR , 0.85 ; 95 % CI , 0.73 - 0.98 ) , less total consumption ( RR , 0.79 ; 95 % CI , 0.64 - 0.97 [ equivalent to 3.0 st and ard drinks per week ] ) , reduced episodic heavy drinking ( RR , 0.65 ; 95 % CI , 0.45 - 0.93 ) , and fewer academic problems ( RR , 0.78 ; 95 % CI , 0.65 - 0.93 ) . At 12 months , statistically significant differences in academic problems remained ( RR , 0.75 ; 95 % CI , 0.62 - 0.90 ) , while the AUDIT scores were 2.02 ( 95 % CI , -0.97 to -3.10 ) points lower . CONCLUSIONS Single-dose e-SBI reduces hazardous drinking , and the effect lasts 12 months . Additional sessions seem not to enhance the effect . Trial Registration www.anzctr.org.au Identifier : ACTRN012607000103460 BACKGROUND University students drink more heavily than their nonstudent peers and are often unaware that their drinking is risky and exceeds normative levels . We tested the efficacy of a proactive Web-based alcohol screening and brief intervention program . METHODS A r and omized controlled trial was conducted at an Australian university in 2007 . Invitations were sent to 13 000 undergraduates ( age range , 17 - 24 years ) to complete a Web-based Alcohol Use Disorders Identification Test . Of 7237 students who responded , 2435 scored in the hazardous/harmful range ( > or = 8) and were r and omized , and 2050 ( 84 % ) completed at least 1 follow-up assessment . Intervention was 10 minutes of Web-based motivational assessment and personalized feedback . Controls received only screening . Follow-up assessment s were conducted at 1 and 6 months with observers and participants blinded to allocation . Outcome measures were drinking frequency , typical occasion quantity , overall volume , number of personal problems , an academic problems score , prevalence of binge drinking , and prevalence of heavy drinking . RESULTS Mean ( SD ) baseline Alcohol Use Disorders Identification Test scores for control and intervention groups were 14.3 ( 5.1 ) and 14.2 ( 5.1 ) , respectively . After 1 month , participants receiving intervention drank less often ( rate ratio [ RR ] , 0.89 ; 95 % confidence interval [ CI ] , 0.83 - 0.94 ) , smaller quantities per occasion ( RR , 0.93 ; 95 % CI , 0.88 - 0.98 ) , and less alcohol overall ( RR , 0.83 ; 95 % CI , 0.78 - 0.90 ) than did controls . Differences in alcohol-related harms were nonsignificant . At 6 months , intervention effects persisted for drinking frequency ( RR , 0.91 ; 95 % CI , 0.85 - 0.97 ) and overall volume ( RR , 0.89 ; 95 % CI , 0.82 - 0.96 ) but not for other variables . CONCLUSION Proactive Web-based screening and intervention reduces drinking in undergraduates , and such a program could be implemented widely OBJECTIVE To evaluate the effectiveness of brief motivational interviewing and an educational brochure when delivered in emergency room to reduce alcohol abuse and related problems among adolescents and young adults . METHOD A r and omized single-blind clinical trial with a three-month follow-up was carried out at three emergency rooms from October 2004 to November 2005 ; subjects assessed were 16 - 25 years old treated for alcohol related events up to 6 hours after consumption . Socio-demographic data , quantity , frequency and negative consequences of alcohol consumption , motivation to change habits and future risk perception were evaluated . Statistical analysis was performed on subjects who completed follow-up ( completers ) . ANCOVA model was used to analyze the difference between the intervention groups with statistical significance level α = 5 % and confidence interval ( CI ) of 95 % . RESULTS 186 subjects formed the initial sample , being 175 included and r and omized to the educational brochure group ( n = 88 ) or motivational interviewing group ( n = 87 ) . Follow-up assessment was performed in 85.2 % of the sample . No significant difference between groups was observed . However , significant reductions ( p < 0.01 ) in related problems and alcohol abuse were found in both groups . CONCLUSION In this sample a reduction of alcohol use and related problems was observed . Preliminary data indicate that controlled clinical trials with motivational interviewing , educational brochure and nonintervention should be of future interest among Brazilian adolescent population To investigate the impact of counselor style , a 2-session motivational checkup was offered to 42 problem drinkers ( 18 women and 24 men ) who were r and omly assigned to 3 groups : ( a ) immediate checkup with directive-confrontational counseling , ( b ) immediate checkup with client-centered counseling , or ( c ) delayed checkup ( waiting-list control ) . Overall , the intervention result ed in a 57 % reduction in drinking within 6 weeks , which was maintained at 1 year . Clients receiving immediate checkup showed significant reduction in drinking relative to controls . The 2 counseling styles were discriminable on therapist behaviors coded from audiotapes . The directive-confrontational style yielded significantly more resistance from clients , which in turn predicted poorer outcomes at 1 year . Therapist styles did not differ in overall impact on drinking , but a single therapist behavior was predictive ( r = .65 ) of 1-year outcome such that the more the therapist confronted , the more the client drank OBJECTIVE St and ardized measures of self-reported alcohol use are the predominant method by which change in alcohol use following interventions is evaluated . This study examined whether the invariance of the test-retest pretreatment Alcohol Use Disorders Identification Test ( AUDIT ) was affected by the treatment experience . In this study , the intervening exposure was to motivational interviewing ( MI ) versus community service ( CS ) , the treatment-as-usual control group . METHOD Analyses were conducted on a sub sample of court-referred 16- to 21-year-olds recruited into a r and omized controlled trial examining the effects of MI on alcohol use and police charges for risky driving and /or drinking . Youths were r and omized to CS or MI . A sub sample of 478 participants , who at baseline completed the AUDIT in reference to alcohol use for the 6 months before their conviction , later repeated the AUDIT at treatment completion , in reference to the same 6-month baseline period . RESULTS At completion of treatment , participants receiving CS had a significant decrease in baseline AUDIT scores , whereas those in MI reported no significant change . The difference between the two groups was significant ( p = .02 ) . Also , of those who reported no drinking before treatment , after receiving MI , 33.5 % changed their response and acknowledged pretreatment drinking , compared with only 8.3 % in CS . CONCLUSIONS These results suggest that treatment received may differentially affect a st and ardized measure of self-reported risky drinking . This effect may be attributable to the treatment experience and /or the experience of the control group . Possible explanations for the effect are explored , including more honesty because of a trusting therapeutic alliance and a response shift bias . Differential change in self-report might affect treatment outcome assessment . Depending on the treatment contrasts , research that relies on pre- to post-treatment changes in self-report may be underestimating treatment effects The aim of this study was to identify whether a brief motivational interviewing and cognitive-behavioural-based alcohol intervention group ( AIG ) programme is feasible with young people at risk of developing a problem with alcohol , and to assess the short-term effectiveness of the intervention . Participants were assigned r and omly to receive a group intervention of four sessions duration ( n=17 ; AIG ) or no treatment ( n=17 , control group ) . Participants were volunteers recruited from a youth centre on the Central Coast of New South Wales , Australia , comprising youths aged 12 - 19 years who were interested in participating in the study . The Readiness to Change Question naire , items from the AUDIT , the DAP Quick Screen and a knowledge question naire were administered at pretreatment , post-treatment and at 1- and 2-month follow-ups . Participants in the AIG programme showed an increase in readiness to reduce their alcohol consumption . They also reduced their frequency of drinking at post-treatment and the first follow-up assessment , while the control group reported increases at the second follow-up assessment . The control group also increased their hazardous drinking and frequency of binge drinking compared to the AIG . The intervention appeared to improve the AIG participants ' knowledge about alcohol and its effects . The results provide preliminary evidence for the effectiveness of the AIG programme in training young people to set limits on alcohol consumption , increase awareness of safe drinking levels and the effects of alcohol abuse . This pilot study also showed that young people who are identified as being ' at risk ' of developing alcohol abuse , and who are also ambivalent about changing drinking behaviours , can be recruited and retained in a treatment programme Motivational interviewing ( MI ) is a counseling style that has been shown to reduce heavy drinking among college students . To date , all studies of MI among college students have used a format that includes a feedback profile delivered in an MI style . This study was a dismantling trial of MI and feedback among heavy-drinking college students . After an initial screen , 279 heavy-drinking students were r and omized to ( a ) Web feedback only , ( b ) a single MI session without feedback , ( c ) a single MI session with feedback , or ( d ) assessment only . At 6 months , MI with feedback significantly reduced drinking , as compared with assessment only ( effect size = .54 ) , MI without feedback ( effect size = .63 ) , and feedback alone ( effect size = .48 ) . Neither MI alone nor feedback alone differed from assessment only . Neither sex , race or ethnicity , nor baseline severity of drinking moderated the effect of the intervention . Norm perceptions mediated the effect of the intervention on drinking . MI with feedback appears to be a robust intervention for reducing drinking and may be mediated by changes in normative perceptions This r and omized controlled trial evaluated the efficacy of a brief intervention design ed to reduce the harmful consequences of heavy drinking among high-risk college students . Students screened for risk while in their senior year of high school ( 188 women and 160 men ) were r and omly assigned to receive an individualized motivational brief intervention in their freshman year of college or to a no-treatment control condition . A normative group selected from the entire screening pool provided a natural history comparison . Follow-up assessment s over a 2-year period showed significant reductions in both drinking rates and harmful consequences , favoring students receiving the intervention . Although high-risk students continued to experience more alcohol problems than the natural history comparison group over the 2-year period , most showed a decline in problems over time , suggesting a developmental maturational effect 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 AIMS This paper describes outcomes from a r and omized controlled trial examining the efficacy of brief interventions delivered by a computer ( CBI ) or therapist ( TBI ) among adolescents in urban primary care clinics . METHODS Patients ( ages 12 - 18 ) self-administered a computer survey . Adolescents reporting past year cannabis use completed a baseline survey and were r and omized to control , CBI or TBI , with primary ( cannabis use , cannabis related consequences - CC ) and secondary outcomes [ alcohol use , other drug use ( illicit and non-medical prescription drugs ) , and driving under the influence of cannabis ( DUI ) ] assessed at 3 , 6 , and 12 months . RESULTS 1416 adolescents were surveyed ; 328 reported past year cannabis use and were r and omized . Comparisons of the CBI relative to control showed that at 3 months the group by time interaction ( G × T ) was significant for other drug use and CC , but not for cannabis use , alcohol use , or DUI ; at 6 months , the G × T interaction was significant for other drug use but not for cannabis use , alcohol use , or CC . For analyses comparing the TBI to control , at 3 months the G × T interaction was significant for DUI , but not significant for cannabis use , alcohol use , or CC ; at 6 months , the G × T interaction was not significant for any variable . No significant intervention effects were observed at 12 months . CONCLUSION Among adolescent cannabis users presenting to primary care , a CBI decreased cannabis related problems and other drug use and a TBI decreased cannabis DUI in the short-term . Additional boosters may be necessary to enhance these reductions over time This study consisted of a r and omized controlled trial of a 1-session motivational intervention for college student binge drinkers . Sixty students who reported binge drinking 2 or more times in the past 30 days were r and omly assigned to either a no-treatment control or a brief intervention group . The intervention provided students with feedback regarding personal consumption , perceived drinking norms , alcohol-related problems , situations associated with heavy drinking , and alcohol expectancies . At 6-week follow-up , the brief intervention group exhibited significant reductions on number of drinks consumed per week , number of times drinking alcohol in the past month , and frequency of binge drinking in the past month . Estimates of typical student drinking mediated these reductions . This study replicates earlier research on the efficacy of brief interventions with college students and extends previous work regarding potential mechanisms of change Interventions to reduce HIV risk behavior have shown promise but have demonstrated inconsistent effects with heterosexual men . This article reports a cognitive-behavioral HIV risk reduction intervention design ed for heterosexually active African American men . Men ( N = 117 ) recruited from a public clinic were r and omly assigned to either ( a ) a 6-hr video-based small group motivational-skills intervention or ( b ) a 6-hr video-based contact-matched HIV education comparison group . Results showed men in the motivational-skills intervention reported lower rates of unprotected vaginal intercourse and higher rates of condom use at the 3-month follow-up . However , because of increased condom use in the comparison condition , differences between groups dissipated 6 months following the intervention . These findings are among the first to demonstrate effects from a motivational-skills intervention for reducing HIV risk in men who have sex with women using a model design ed to facilitate transferring prevention technology to community setting Objective of the study is to assess the efficacy of a brief motivational enhancement intervention in adolescents referred to psychiatric treatment who reported substance-use . In a sample of adolescents ( n = 237 ) consecutively admitted to a psychiatry department , 143 were identified as users . Subjects were r and omly allocated to one of two groups : an experimental group that received a brief intervention aim ed at increasing their awareness of the risks of substance-use , or a control group . All subjects received st and ard treatment according to the primary diagnosis . Structured question naires assessing knowledge , problems , perception of risks and intention of use of psychoactive substances were administered upon admission and 1 month later . Fifty-nine subjects entered the experimental group and 44 the control group . No significant differences between the two groups were identified in socio-demographic features or substance-use . Non-parametric analyses showed a significant increase across time in overall knowledge about drugs and perception of risk in the experimental group ( P < 0.05 ) . A significant increase in overall knowledge in the experimental group compared to controls was found ( P < 0.05 ) . No differences were observed for other variables such as intention of use or perception of risk . Brief intervention in adolescents entering psychiatric treatment led to a significant change in overall knowledge about psychoactive substances but not in other variables related to use . Our results point to the need of more intensive interventions OBJECTIVE This study evaluated the relative efficacy of personalized drinking feedback ( PDF ) delivered with and without a motivational interview ( MI ) for college student drinkers . METHOD Heavy-drinking college students ( N = 54 ; 691 % female ) were identified from a large screening sample and r and omly assigned either to receive PDF during a single MI session or to receive PDF without an MI . Of these participants , 51 ( 94 % ) completed a 6-month follow-up assessment that included measures of alcohol consumption and alcohol-related problems . RESULTS At 6-months postintervention , participants in both groups showed significant , small to moderate reductions in alcohol consumption , but the groups did not differ . Women showed larger reductions than men . Rates of alcohol-related problems remained relatively unchanged . CONCLUSIONS The hypothesis that an MI would enhance the efficacy of PDF was not supported The short-term results of a r and omized trial testing a brief feedback and motivational intervention for substance use among homeless adolescents are presented . Homeless adolescents ages 14 - 19 ( N = 285 ) recruited from drop-in centers at agencies and from street intercept were r and omly assigned to either a brief motivational enhancement ( ME ) group or 1 of 2 control groups . The 1-session motivational intervention presented personal feedback about patterns of risks related to alcohol or substance use in a style consistent with motivational interviewing . Follow-up interviews were conducted at 1 and 3 months postintervention . Youths who received the motivational intervention reported reduced illicit drug use other than marijuana at 1-month follow-up compared with youths in the control groups . Treatment effects were not found with respect to alcohol or marijuana . Post hoc analyses within the ME group suggested that those who were rated as more engaged and more likely to benefit showed greater drug use reduction than did those rated as less engaged . Limitations of the study are discussed as are implication s for development of future substance use interventions for this high-risk group OBJECTIVE The aim of this study was to investigate the effectiveness of a brief intervention for m and ated students in the context of the University Assistance Program , a Student Assistance Program developed and modeled after workplace Employee Assistance Programs . METHOD Participants were 265 ( 196 males and 69 females ) judicially m and ated college students enrolled in a large , urban university in the northeast United States . All participants were sanctioned by the university 's judicial office for an alcohol- or drug-related violation . Participants were r and omized to one of two intervention conditions ( the University Assistance Program or services as usual ) and were assessed at baseline and 3 and 6 months after intervention . RESULTS Growth curve analyses showed that , relative to services as usual , the University Assistance Program was more efficacious in reducing past-90-day weekday alcohol consumption and the number of alcohol-related consequences while increasing past-90-day use of protective behaviors and coping skills . No significant differences in growth trajectories were found between the two intervention conditions on past-90-day blood alcohol concentration , total alcohol consumption , or weekend consumption . CONCLUSIONS The University Assistance Program may have a possible advantage over services as usual for m and ated students OBJECTIVE Over the past 2 decades , colleges and universities have seen a large increase in the number of students referred to the administration for alcohol policies violations . However , a substantial portion of m and ated students may not require extensive treatment . Stepped care may maximize treatment efficiency and greatly reduce the dem and s on campus alcohol programs . METHOD Participants in the study ( N = 598 ) were college students m and ated to attend an alcohol program following a campus-based alcohol citation . All participants received Step 1 : a 15-min brief advice session that included the provision of a booklet containing advice to reduce drinking . Participants were assessed 6 weeks after receiving the brief advice , and those who continued to exhibit risky alcohol use ( n = 405 ) were r and omized to Step 2 , a 60- to 90-min brief motivational intervention ( n = 211 ) , or an assessment -only control ( n = 194 ) . Follow-up assessment s were conducted 3 , 6 , and 9 months after Step 2 . RESULTS Results indicated that the participants who received a brief motivational intervention showed a significantly reduced number of alcohol-related problems compared to those who received assessment only , despite no significant group differences in alcohol use . In addition , low-risk drinkers ( n = 102 ; who reported low alcohol use and related harms at 6-week follow-up and were not r and omized to stepped care ) showed a stable alcohol use pattern throughout the follow-up period , indicating they required no additional intervention . CONCLUSION Stepped care is an efficient and cost-effective method to reduce harms associated with alcohol use by m and ated students OBJECTIVE Behavioral economic theory suggests that a reduction in substance use is most likely when there is an increase in rewarding substance-free activities . The goal of this r and omized controlled clinical trial was to evaluate the incremental efficacy of a novel behavioral economic supplement ( Substance-Free Activity Session [ SFAS ] ) to a st and ard alcohol brief motivational interviewing ( BMI ) session for heavy-drinking college students . METHOD Participants were 82 first-year college students ( 50 % female ; 81.7 % White/European American ; M age = 18.5 years , SD = 0.71 ) who reported 2 or more past-month heavy drinking episodes . After completing a baseline assessment and an individual alcohol-focused BMI , participants were r and omized to either the SFAS or to a Relaxation Training ( RT ) control session . The SFAS was delivered in an MI style and attempted to increase the salience of delayed academic and career rewards and the patterns of behavior leading to those rewards . RESULTS The combination of an alcohol BMI plus the SFAS was associated with significantly greater reductions in alcohol problems compared with an alcohol BMI plus RT at the 1-month and 6-month follow-up assessment s ( p = .015 , ηp² = .07 ) , an effect that was partially mediated by increases in protective behavioral strategies . BMI + SFAS was also associated with greater reductions in heavy drinking among participants who at baseline reported low levels of substance-free reinforcement or symptoms of depression . CONCLUSION These results are consistent with behavioral economic theory and suggest that a single session focused on increasing engagement in alternatives to drinking can enhance the effects of brief alcohol interventions OBJECTIVE The study aim was to test whether a brief motivational intervention , with or without a booster session , would improve drinking-related outcomes more than st and ard Emergency Department ( ED ) treatment . METHOD The study population consisted of 539 ( 78 % male ) injured patients treated in the ED and discharged to the community following their treatment . Injured patients met inclusion criteria if they were assessed as hazardous or harmful drinkers by scoring eight or more on the AUDIT and /or having alcohol in their system at the time of their injury or ED visit . Patients were r and omly assigned to either st and ard care ( SC ) , brief intervention ( BI ) or brief intervention plus a booster session ( BIB ) . At 1-year follow-up , 447 patients ( 83 % of the sample ) were re-interviewed to measure alcohol-related negative consequences , injuries and drinking . RESULTS Patients receiving BIB , but not B1 patients , reduced alcohol-related negative consequences and alcohol-related injuries more than did those in the SC group . All three groups reduced their days of heavy drinking . Patients with histories of hazardous drinking responded to BIB , whether or not they had consumed alcohol prior to their injury . CONCLUSIONS Together , these results indicate that the effects of a booster session that is added to a brief intervention in the ED can be helpful to injured patients with a history of hazardous or harmful drinking , irrespective of whether they have consumed alcohol prior to their injury Individual brief motivational intervention ( i BMI ) is an efficacious strategy to reduce heavy drinking by students who are m and ated to receive an alcohol intervention following an alcohol-related event . However , despite the strong empirical support for i BMI , it is unknown if the results from rigorously controlled research on i BMI translate to real-world setting s. Furthermore , many colleges lack the re sources to provide i BMI to m and ated students . Therefore , group-delivered BMI ( g BMI ) might be a cost-effective alternative that can be delivered to a large number of individuals . The purpose of this study was to conduct a comparative effectiveness evaluation of i BMI and g BMI as delivered by staff at a university health services center . Participants ( N = 278 ) were college students who were m and ated to receive an alcohol intervention following an alcohol-related incident . Participants were r and omized to receive an individual ( i BMI ; n = 133 ) or a Group BMI ( g BMI ; n = 145 ) . Results indicated that both i BMI and g BMI participants reduced their peak estimated blood alcohol concentration ( BAC ) and the number of negative alcohol-related consequences at 1- , 3- , and 6-months postintervention . The i BMI and g BMI conditions were not significantly different at follow-up . These findings provide preliminary support for the use of i BMI and g BMI s for college students in real-world setting OBJECTIVE Brief interventions for college student drinkers have been shown to be effective in reducing the amount of alcohol consumed as well as the number of alcohol-related problems . However , the duration of brief interventions varies substantially across studies . METHOD In the present study 114 undergraduate students who drank alcohol heavily were r and omly assigned to a 10-minute brief intervention , a 50-minute brief intervention , or assessment -only control . The content of the active interventions was based on the same concept , and both interventions incorporated motivational interviewing components . Participants were assessed at baseline and 4-week post intervention on quantity of alcohol use , alcohol-related problems , and protective behavioral strategies . RESULTS As hypothesized , there was a significant difference between participants in the 10-minute intervention and control condition regarding their alcohol consumption at 4-week follow up . However , there was no significant difference between the 50-minute intervention and the control condition on alcohol consumption . There were also no significant differences between active intervention conditions , and neither intervention showed advantages for reducing problems or increasing protective behaviors relative to the control condition . CONCLUSIONS Results suggest a very brief intervention can impact short-term alcohol use outcomes , with potentially no advantage of longer interventions for this population This study evaluated the impact of a motivational interview ( MI ) on alcohol use in underage college drinkers , and examined the specific role of empathy and alliance in MI . Fifty-five underage heavy drinkers were r and omized to a one-session MI or no-treatment control . Empathy and alliance were evaluated through the MITI , participant , and therapist ratings . At two-month follow-up , multivariate tests reveal no significant interaction effects . Means comparisons indicated that both groups showed reductions in alcohol-related problems , however , only the MI sample evidence d significant reductions in binge drinking . In addition , despite the reductions of both groups , effect sizes indicated that the MI group outperformed the control in terms of binge-drinking and alcohol-related problems . Contrary to predictions , empathy and alliance showed no relationships with outcomes This study is the first reported test of the unique and combined effects of Brief Motivational Intervention ( BMI ) and Alcohol Expectancy Challenge ( AEC ) with heavy drinking college students . Three hundred and thirty-five participants were r and omly assigned in a 2x2 factorial design to either : BMI , AEC , BMI and AEC , and assessment only conditions . Follow-ups occurred at 1 , 3 , and 6 months . Unconditional latent curve analyses suggested that alcohol use ( Q-F ) , heavy episodic drinking , and alcohol problems were best modeled as quadratic effects . BMI produced significant decreases in Q-F , heavy drinking , and problems , while AEC produced significant decreases in Q-F and heavy drinking . There was no evidence of an additive effect of combining the interventions . Intervention effects decayed somewhat for BMI and completely for AEC over 6 months . Multi-group analyses suggested similar intervention effects for men and women . BMI effects on alcohol problems were mediated by perceived norms . These findings extend previous research with BMI and AEC but do not support their utility as a combined preventive intervention to reduce collegiate alcohol abuse The Lifestyle Management Class ( LMC ) was evaluated as a universal and targeted alcohol prevention program among voluntary and m and ated college students . The relative efficacy of peer- and professional-led group interventions was also tested in this r and omized , controlled design . LMC participants showed decreases in driving after drinking relative to control participants . Changes in heavy drinking varied as a function of treatment condition , readiness to change , and gender , with a trend toward larger decreases among voluntary LMC participants high in readiness to change and a comparable though nonsignificant advantage for male LMC participants in the m and ated sample . The LMC was comparably effective for m and ated and voluntary students , with no clear advantage for peer- or professional-led groups OBJECTIVES : This study examined the efficacy of emergency department (ED)-based brief interventions ( BIs ) , delivered by a computer or therapist , with and without a post-ED session , on alcohol consumption and consequences over 12 months . METHODS : Patients ( ages 14–20 years ) screening positive for risky drinking were r and omized to : BI ( n = 277 ) , therapist BI ( n = 278 ) , or control ( n = 281 ) . After the 3-month follow-up , participants were r and omized to receive a post-ED BI session or control . Incorporating motivational interviewing , the BIs addressed alcohol consumption and consequences , including driving under the influence ( DUI ) , and alcohol-related injury , as well as other concomitant drug use . The computer BI was an offline , Facebook-styled program . RESULTS : Among 4389 patients screened , 1054 patients reported risky drinking and 836 were enrolled in the r and omized controlled trial . Regression models examined the main effects of the intervention conditions ( versus control ) and the interaction effects ( ED condition × post-ED condition ) on primary outcomes . The therapist and computer BIs significantly reduced consumption at 3 months , consequences at 3 and 12 months , and prescription drug use at 12 months ; the computer BI reduced the frequency of DUI at 12 months ; and the therapist BI reduced the frequency of alcohol-related injury at 12 months . The post-ED session reduced alcohol consequences at 6 months , benefiting those who had not received a BI in the ED . CONCLUSIONS : A single-session BI , delivered by a computer or therapist in the ED , shows promise for underage drinkers . Findings for the fully automated st and -alone computer BI are particularly appealing given the ease of future implementation OBJECTIVES : Criminally involved adolescents engage in high levels of alcohol-related risky sex . A theory-based sexual and alcohol risk-reduction intervention was design ed , implemented , and evaluated in juvenile detention facilities . Participants and Methods . In a r and omized , controlled trial , 484 detained adolescents received 1 of 3 group-based interventions : combined sexual and alcohol risk reduction ( group psychosocial intervention [ GPI ] + group motivational enhancement therapy [ GMET ] ) ; sexual risk reduction only ( GPI ) ; or HIV/sexually transmitted disease prevention information only ( group information-only intervention [ GINFO ] ) . Follow-up data were obtained 3 , 6 , 9 , and 12 months after the intervention . Behavioral outcomes were condom-use behavior , frequency of intercourse while drinking , and alcohol-related problems . RESULTS : Condom-use behavior measured as frequency of condom use during sex ( ranging from never to always ) decreased over time , although the GPI and GPI + GMET interventions mitigated this tendency at the 3- , 6- , and 9-month follow-up assessment s. Although both active interventions were significantly more successful than the GINFO condition and the pattern of effects favored the GPI + GMET , there were no statistically significant differences between the GPI and GPI + GMET interventions . CONCLUSIONS : Findings support the feasibility of integrating alcohol-specific sexual risk content into a theory-based sexual risk-reduction intervention and provide additional evidence that theory-based interventions are effective at reducing risky sex in this population . There was limited evidence of intervention effects on alcohol-use outcomes . Future research should focus on strengthening the GPI + GMET to most effectively target risky sexual behavior among at-risk adolescents OBJECTIVE The current study tested the efficacy of a brief intervention design ed to reduce drinking and drinking-related consequences among first-year fraternity members . METHOD Twelve fraternities were r and omly assigned to receive either a motivational enhancement intervention with individual and housewide feedback components ( n = 6 houses ) or a treatment-as-usual control condition ( n = 6 houses ) . Individual feedback was delivered either by peer interviewers or professional research staff . Participants were assessed during their pledge ( first ) year of house membership and during a follow-up period 1 year later . RESULTS Of the participants who completed follow-up ( N = 120 ) , fraternity members who received the brief intervention reported significant reductions in alcohol use ( total average consumption ) and typical peak blood alcohol concentrations when compared with fraternity members in the control condition . No differences in drinking-related consequences were observed . Fraternity members who received their individualized feedback from peer interviewers and professional members of the research staff reported similar outcomes . CONCLUSIONS Results provide support for the efficacy of a brief motivational enhancement intervention in reducing drinking within this high-risk population . The cost-effective use of peer interviewers appears to be a promising strategy for delivering individualized prevention programming in college population OBJECTIVE College students are an at-risk population for heavy drinking and negative alcohol-related outcomes . Research has established that brief , multicomponent motivational interviewing-based interventions can be effective at reducing alcohol use or related problems , but less is known about the efficacy of individual components within these interventions . The purpose of this study was to test the efficacy of 2 single-component , in-person , brief ( 15 - 20 min ) alcohol interventions : personalized normative feedback ( PNF ) and protective behavioral strategies feedback ( PBSF ) . METHOD Data were collected on 365 undergraduate students from a large Midwestern university ( 65 % women ; 89 % White ) who were r and omly assigned to 1 of 3 conditions : PNF , PBSF , or alcohol education ( AE ) . Participants completed measures of alcohol use , alcohol-related problems , social norms , and protective behavioral strategies . RESULTS Results indicated that the PNF intervention was efficacious relative to the other conditions at reducing alcohol use and that its effects at 6-month follow-up were mediated by changes in perceived norms at the 1-month follow-up . The PBSF intervention was not efficacious at reducing alcohol use or alcohol-related problems . CONCLUSIONS These findings provide support for the efficacy of an in-person PNF intervention and theoretical support for the hypothesized mechanisms of change in the intervention . Implication s for research ers and clinicians are discussed R. Lorraine Collins State University of New York at Stony Brook George A. Parks and G. Alan Marlatt University of Washington Two studies were conducted to assess variables related to the social determinants of alcohol consumption . In Study 1 , moderate- and heavy-drinking male under- graduates were paired with confederates who behaved in a sociable or unsociable manner while modeling either light or heavy consumption . Modeling occurred in the sociable conditions but not in the unsociable conditions , where subjects tended to drink heavily . In Study 2 , a similar group of subjects was exposed to one of three social status conditions crossed with light versus heavy consumption . The results indicated a modeling effect in all social status conditions . These studies provide further support for the existence of a modeling effect that can be disrupted by a lack of rapport between drinking partners . This latter finding has implication s for the etiology of problem drinking because it suggests that increased alcohol consumption may serve as a strategy for coping with aversive social interactions . Initial research on the effect of modeled consumption rates on social drinking ( Caudill & Marlatt , 1975 ) suggested that heavy-drink- ing men tended to match the consumption of their drinking partner whether his con- sumption was heavy or light . Subsequent examinations of this phenomenon replicated these findings in laboratory analogue drinking tasks such as the taste-rating task ( Cooper , Waterhouse , & Sobell , 1979 ; Hendricks , So- bell , & Cooper , 1978 ; Lied & Marlatt , 1979 ; Watson & Sobell , 1982 ) , natural bar setting s ( Reid , 1978 ) , and seminaturalistic bar setting s ( Caudill & Lipscomb , 1980 ) . Much of the research concerning the mod- eling of alcohol consumption has focused on manipulating characteristics of the model , including the nature of the social interaction between the model and the subject . The effects of manipulating social interaction are unclear . In the Caudill and Marlatt study , model 's drinking rate ( light vs. heavy ) and OBJECTIVE Using a r and omized factorial design , we examined the efficacy of a brief motivational intervention ( BMI ) and a parent-based intervention ( PBI ) as universal preventive interventions to reduce alcohol use among incoming college students . METHOD Participants ( N = 1,014 ) were assessed prior to matriculation and at 10 months and 22 months postbaseline . Two-part latent growth modeling was used to simultaneously examine initiation and growth in heavy episodic drinking and alcohol-related consequences . RESULTS This study retained 90.8 % ( n = 921 ) of r and omized students at the 10-month follow-up and 84.0 % ( n = 852 ) of r and omized students at the 22-month follow-up . BMI participants were significantly less likely than non- BMI participants to initiate heavy episodic drinking and to begin experiencing alcohol-related consequences . Effect sizes were minimal at 10 months ( Cohen 's h ranged from 0.02 to 0.07 ) and were small at 22 months ( hs ranged from 0.15 to 0.22 ) . A significant BMI x PBI interaction revealed that students receiving both the BMI and the PBI were significantly less likely to report the onset of consequences beyond the sum of the individual intervention effects ( h = 0.08 at 10 months , and h = 0.21 at 22 months ) . Hypothesized direct BMI effects for reductions in heavy episodic drinking and consequences were not observed . Significant mediated effects via changes in descriptive norms were present for both growth and initiation of heavy episodic drinking and consequences . CONCLUSIONS To our knowledge , the current study is the first to provide support for BMI as a universal preventive intervention for incoming college students . Although hypothesized PBI main effects were not found , mediation analyses suggest future refinements could enhance PBI effectiveness We tested whether a brief motivational interview ( MI ) would reduce alcohol-related consequences and use among adolescents treated in an emergency department ( ED ) after an alcohol-related event . Patients aged 13 to 17 years ( N = 152 ) with a positive blood alcohol concentration ( BAC ) by lab test or self-report were recruited in the ED and r and omly assigned to receive either MI or st and ard care ( SC ) . Both conditions result ed in reduced quantity of drinking during the 12-month follow-up , whereas alcohol-related negative consequences were relatively low and stayed low at follow-up . Adolescents who screened positive for problematic alcohol use at baseline reported significantly more improvement on 2 of 3 alcohol use outcomes ( average number of drinking days per month and frequency of high-volume drinking ) if they received MI compared with SC . We conclude that brief interventions are recommended for adolescents who present to an ED with an alcohol-related event and report preexisting problematic alcohol use This study tested the hypothesis that client choice influences intervention outcomes . We recruited 288 student drinkers ( 60 % men , 67 % freshmen ) required to participate in an intervention due to a violation of campus alcohol policy . Participants were r and omized either to self-chosen or research er-assigned interventions . In the choice condition they selected either a brief motivational intervention ( BMI ) or a computer-delivered educational program . In the assigned condition they received 1 of the 2 interventions , assigned r and omly . Follow-up assessment s at 1 and 2 months revealed that choice was associated with higher intervention satisfaction . However , the assigned and choice conditions did not differentially change on consumption or consequences across intervention type . Overall , change scores favored the BMI over the computer-delivered intervention on consumption and consequences . Exploratory analyses revealed that given the choice of intervention , heavier-drinking students self-selected into the face-to-face BMI . Furthermore , among the students who received a BMI , the students who chose it ( despite their heavier drinking ) reduced drinks per drinking day more than did the assigned students . In summary , offering a choice of intervention to students m and ated for campus alcohol violations increased the chance that at-risk students will select a more intensive and effective intervention Healthy Choices , a four-session motivational interviewing-based intervention , reduces risk behaviors among US youth living with HIV ( YLWH ) . We r and omized 110 Thai YLWH ( 16–25 years ) to receive either Healthy Choices or time-matched health education ( Control ) over 12 weeks . Risk behaviors were assessed at baseline , 1 , and 6 months post-session . The pilot study was not powered for between-group differences ; there were no statistical differences in sexual risks , alcohol use , and antiretroviral adherence between the two groups at any visit . In within-group analyses , Healthy Choices group demonstrated decreases in the proportion of HIV-negative partners ( 20 vs 8.2 % , P = 0.03 ) and HIV sexual risk scores ( 4.3 vs 3.3 , P = 0.04 ) , and increased trends in the proportion of protected sex ( 57 vs 76.3 % , P = 0.07 ) from baseline to 1 month post-session . These changes were not sustained 6 months later . No changes were observed in Control group . Healthy Choices has potential to improve sexual risks among Thai YLWH BACKGROUND Drug use among parenting women is a significant risk factor for a range of negative child outcomes , including exposure to violence , child maltreatment , and child behavior problems . Implementation of brief interventions with this population may be greatly facilitated by computer-based interventions . DESIGN R and omized clinical trial with 4-month follow-up . SETTING / PARTICIPANTS Participants were 107 postpartum women recruited from an urban obstetric hospital primarily serving a low-income population . Women were r and omized into assessment only versus assessment plus brief intervention conditions ; 76 ( 71 % ) returned for follow-up evaluation . INTERVENTION A 20-minute , single-session , computer-based motivational intervention ( based on motivational interviewing methods ) , combined with two nontailored mailings and voucher-based reinforcement of attendance at an initial intake/treatment session . MAIN OUTCOME MEASURES Illicit drug use as measured by qualitative urinalysis and self-report . RESULTS Frequency of illicit drug use other than marijuana increased slightly for the control group , but declined among intervention group participants ( p<0.05 , between-group Mann-Whitney U ; d=0.50 ) ; the magnitude of intervention effects on changes in marijuana use frequency was similar , but did not reach statistical significance . Point-prevalence analysis at follow-up did not show significant group differences in drug use . However , trends under a range of assumptions regarding participants lost to follow-up all favored the intervention group , with most effect sizes in the moderate range ( odds ratios 1.4 to 4.7 ) . CONCLUSIONS Results tentatively support the efficacy of this high-reach , replicable brief intervention . Further research should seek to replicate these findings and to further develop the computer as a platform for vali date d brief interventions Heavy drinking among college students is common and is often harmful . A previously reported r and omized trial revealed that a brief motivational intervention ( BMI ) reduced the alcohol consumption of heavy drinking college students ( K. B. Carey , M. P. Carey , S. A. Maisto , & J. M. Henson , 2006 ) . For this study , the research ers conducted supplemental analyses of hypothesized predictors of change using the same sample ( N = 495 ) . Greater readiness to change , higher levels of self-regulation , and less engagement in social comparison all independently predicted reductions in drinking outcomes . Furthermore , self-regulation , social comparison , and future time perspective interacted with BMI and predicted drinks per week . As expected , greater self-regulation skills enhanced response to the BMI ; the remaining interaction effects were unexpected . Overall , these findings suggest that BMI s produce relatively robust effects OBJECTIVE The current study is a multisite r and omized alcohol prevention trial to evaluate the efficacy of both a parenting h and book intervention and the Brief Alcohol Screening and Intervention for College Students ( BASICS ) intervention , alone and in combination , in reducing alcohol use and consequences among a high-risk population of matriculating college students ( i.e. , former high school athletes ) . METHOD Students ( n = 1,275 ) completed a series of Web-administered measures at baseline ( in the summer before starting college ) and follow-up ( after 10 months ) . Students were r and omized to one of four conditions : parent intervention only , BASICS only , combined ( parent and BASICS ) , and assessment -only control . Intervention efficacy was tested on a number of outcome measures , including peak blood alcohol concentration , weekly and weekend drinking , and negative consequences . Hypothesized mediators and moderators of intervention effect were tested . RESULTS The overall results revealed that the combined-intervention group had significantly lower alcohol consumption , high-risk drinking , and consequences at 10-month follow-up , compared with the control group , with changes in descriptive and injunctive peer norms mediating intervention effects . CONCLUSIONS The findings of the present study suggest that the parent intervention delivered to students before they begin college serves to enhance the efficacy of the BASICS intervention , potentially priming students to respond to the subsequent BASICS session OBJECTIVES This study examined long-term response to an individual preventive intervention for high-risk college drinkers relative to the natural history of college drinking . METHODS A single-session , individualized preventive intervention was evaluated within a r and omized controlled trial with college freshmen who reported drinking heavily while in high school . An additional group r and omly selected from the entire screening pool provided a normative comparison . Participant self-report was assessed annually for 4 years . RESULTS High-risk controls showed secular trends for reduced drinking quantity and negative consequences without changes in drinking frequency . Those receiving the brief preventive intervention reported significant additional reductions , particularly with respect to negative consequences . Categorical individual change analyses show that remission is normative , and they suggest that participants receiving the brief intervention are more likely to improve and less likely to worsen regarding negative drinking consequences . CONCLUSIONS Brief individual preventive interventions for high-risk college drinkers can achieve long-term benefits even in the context of maturational trends OBJECTIVE Brief interventions for hazardous and low-dependent drinkers in the primary care setting have considerable empirical support . The purpose of this study was to ( 1 ) evaluate the effects of brief advice ( BA ) and motivational enhancement ( ME ) interventions on alcohol consumption . In addition , a hindsight matching design was used to ( 2 ) study the moderator effects of patient readiness to change ( alcohol use ) on alcohol consumption . METHOD The subjects ( N = 301 , 70 % men ) were patients 21 years of age or older who presented for treatment at one of 12 primary care clinics . After screening for eligibility and providing consent to participate in the study , the patients completed a baseline assessment and were r and omly assigned to the BA , ME or st and ard care ( SC ) interventions condition . Follow-up assessment s were completed at 1- , 3- , 6- , 9- and 12-months postbaseline assessment . RESULTS Evaluation of the first hypothesis ( n = 232 for these analyses ) showed that all participants tended to reduce their alcohol use considerably between the baseline and 12-month assessment s. In addition , evaluation of the second hypothesis showed a moderator effect of readiness to change in predicting the number of drinks at 12 months , such that the BA intervention seemed more effective for patients relatively low in readiness to change compared to those higher in readiness . Readiness to change did not seem to be related to changes in drinking of participants in the SC or ME conditions . CONCLUSIONS The results confirm that , among primary care patients , substantial changes in alcohol consumption are possible . They further suggest that matching studies of patient readiness to change their alcohol use , as well as other variables , are warranted The present study tested the proposition that an intervention to reduce alcohol use among college students will also reduce their risky sexual behavior . In a r and omized controlled trial , 154 heavy-drinking , predominantly White , heterosexual college students at behavioral risk for infection with HIV and other sexually transmitted diseases were assigned to receive no intervention or a two-session , in-person , motivational interviewing-based intervention focused on ( a ) reducing alcohol risk behavior , ( b ) reducing HIV risk behavior , or ( c ) reducing both alcohol and HIV risk behavior . Three-month retrospective assessment s of alcohol use and sexual behavior were conducted at intake and at 3- , 6- , 9- , 12- , and 15-month follow-up appointments . During follow-up , participants who received the single-focus alcohol risk-reduction intervention drank less frequently and consumed fewer drinks per drinking day as compared with no-intervention control participants , but did not differ from control participants in their frequency of intercourse without a condom or number of sexual partners . Participants who received the single-focus HIV risk-reduction intervention evidence d fewer unprotected sex events during follow-up , as compared with control participants . The number of sexual partners reported during follow-up did not differ by condition . Effects of the interventions did not vary significantly over time and were not moderated by participant gender . Results suggest that intervening to reduce alcohol use may not reduce risky sexual behavior among nonminority college students , but that a brief motivational intervention targeting HIV risk behavior may have utility for reducing the frequency of unprotected sex in this population BACKGROUND It is known that brief interventions for m and ated college students decrease alcohol use and /or related problems in the short term . However , none of the existing studies has followed students ' past 6 months . Therefore , we compared the long-term efficacy of 2 brief substance use feedback interventions for m and ated college students . METHODS We followed up m and ated students ( N=348 ) who were r and omly assigned to either a brief motivational interview ( BMI ; n=180 ) or a written feedback-only ( WF ; n=168 ) intervention at 4 months and 15 months postintervention . RESULTS Long-term follow-up data revealed that students , at the aggregate level , decreased their peak blood alcohol concentration ( BAC ) levels , number of drinks per week , and number of alcohol-related problems at 15 months postintervention compared with their baseline levels . With the exception of peak BAC , the observed long-term reduction was mainly due to the positive change among students who received the BMI intervention . Students in the BMI intervention showed significantly lower levels of alcohol-related problems at 15 months than those in the WF intervention . The BMI intervention more effectively reduced within-individual alcohol-related problems during the initial 4 months , and more successfully curbed the subsequent increase in alcohol use frequency and number of drinks per week during the 11 months between the 2 follow-up assessment s. CONCLUSIONS The results suggest that brief substance use interventions reduce the riskiest type of alcohol use ( e.g. , peak BAC ) among m and ated college students over the long term , and that sleeper effects of in-person personal feedback interventions ( PFIs ) exist . In-person PFIs in the context of a motivational interview may be more efficacious in the long term than written feedback-only interventions for m and ated students . Future studies comparing interventions for college students should extend follow-up for longer periods of time This study evaluated the efficacy of an alcohol web-based personalized feedback program delivered in the workplace to young adults . Participants ( N = 124 ) were r and omly assigned to one of three conditions : web-based feedback ( WI ) , web-based feedback plus a 15-minute motivational interviewing session ( MI ) , or a control group . Results indicated that participants in the intervention group ( WI and MI conditions combined ) reported significantly lower levels of drinking than those in the control group at a 30-day follow-up . This was particularly true for participants classified as high-risk drinkers at the baseline assessment . Similar results were found when comparing the WI condition to the control group . No differences were found between the WI and MI conditions , indicating that the addition of a 15-minute motivational interviewing session did not increase the efficacy of the web-based feedback program . Findings support the use of web-based feedback as a st and -alone alcohol prevention program for young adults in the workplace This study tested the feasibility and efficacy of a brief smoking intervention for adolescents in a hospital setting . Forty adolescent patients were r and omized to receive either brief advice or a motivational interview , a nonconfrontational therapeutic intervention . Feasibility of brief smoking interventions with teen patients was supported by high rates of recruitment , retention , and quit attempts , and long periods of continuous abstinence . Although between-groups differences on smoking measures were not significant at 3-month follow-up , an effect size of h = .28 was noted . The sample showed significant decreases in smoking dependence and number of days smoked . Baseline stage of change , smoking rate , and depression were significant prospect i ve predictors of smoking outcome . Implication s for smoking intervention research with adolescents are discussed The purpose of this study was to evaluate the efficacy of two brief interventions and the inclusion of a 1-month booster session with college students who were referred to attend alcohol education following an alcohol-related incident . Participants ( N=225 ; 48.9 % male ) were r and omly assigned to receive one session of a Brief Motivational Interview ( BMI ) or computer-delivered intervention ( CDI ) with the Alcohol 101 CD-ROM . Participants were also r and omly assigned to booster/no booster . At 3-month follow up , participants in BMI reported greater help seeking and use of behavioral strategies to moderate drinking . At 12-month follow up , BMI participants were drinking more frequently and CDI participants were consuming a greater number of drinks per occasion than at baseline . Mediation analyses showed that the use of specific behavioral strategies mediated the effect of the BMI condition on drinking volume . There was no intervention effect on alcohol problems , and the booster condition did not significantly affect outcomes . Promoting specific behaviors in the context of in-person brief interventions may be a promising approach to reducing drinking volume among identified at-risk students This study evaluated the use of a brief motivational interview ( MI ) to reduce alcohol-related consequences and use among adolescents treated in an emergency room ( ER ) following an alcohol-related event . Patients aged 18 to 19 years ( N = 94 ) were r and omly assigned to receive either MI or st and ard care ( SC ) . Assessment and intervention were conducted in the ER during or after the patient 's treatment . Follow-up assessment s showed that patients who received the MI had a significantly lower incidence of drinking and driving , traffic violations , alcohol-related injuries , and alcohol-related problems than patients who received SC . Both conditions showed reduced alcohol consumption . The harm-reduction focus of the MI was evident in that MI reduced negative outcomes related to drinking , beyond what was produced by the precipitating event plus SC alone The authors conducted two r and omized clinical trials with ethnically diverse sample s of college student drinkers in order to determine ( a ) the relative efficacy of two popular computerized interventions versus a more comprehensive motivational interview approach ( BASICS ) and ( b ) the mechanisms of change associated with these interventions . In Study 1 , heavy drinking participants recruited from a student health center ( N = 74 , 59 % women , 23 % African American ) were r and omly assigned to receive BASICS or the Alcohol 101 CD-ROM program . BASICS was associated with greater post-session motivation to change and self-ideal and normative discrepancy relative to Alcohol 101 , but there were no group differences in the primary drinking outcomes at 1-month follow-up . Pre to post session increases in motivation predicted lower follow-up drinking across both conditions . In Study 2 , heavy drinking freshman recruited from a core university course ( N = 133 , 50 % women , 30 % African American ) were r and omly assigned to BASICS , a web-based feedback program ( e-CHUG ) , or assessment -only . BASICS was associated with greater post-session self-ideal discrepancy than e-CHUG , but there were no differences in motivation or normative discrepancy . There was a significant treatment effect on typical weekly and heavy drinking , with participants in BASICS reporting significantly lower follow-up drinking relative to assessment only participants . In Study 2 , change in the motivation or discrepancy did not predict drinking outcomes . Across both studies , African American students assigned to BASICS reported medium effect size reductions in drinking whereas African American students assigned to Alcohol 101 , e-CHUG , or assessment did not reduce their drinking AIMS To investigate whether a stimulant- and alcohol-focused brief motivational intervention induces positive behaviour change among young , regular users of MDMA ( ' ecstasy ' ) , cocaine powder and crack cocaine . DESIGN AND MEASUREMENTS A r and omized trial of the intervention versus a control group who received written health risk information material s only . All participants completed a baseline self- assessment question naire before r and omization . Outcome measures were self-reported period prevalence abstinence from ecstasy , cocaine powder and crack cocaine and the frequency and amount of stimulant and alcohol use in the previous 90 days , recorded at 6-month follow-up via self-completion question naire and personal interview . PARTICIPANTS AND SETTING A total of 342 adolescent and young adult stimulant users ( aged 16 - 22 years ) were recruited and 87 % were followed-up . The intervention was delivered by a team of 12 agency youth drug workers and two research ers at five locations in Greater London and south-east Engl and . FINDINGS There were no significant differences in abstinence for ecstasy , cocaine powder or crack cocaine use between the experimental and control groups . Contrasting follow-up with baseline self-reports , there were no between-group effects for changes in the frequency or amount of stimulant or alcohol use . Participant follow-up data suggested that the baseline assessment was a contributing factor in within-group behaviour change among experimental and control condition participants . CONCLUSIONS Our brief motivational intervention was no more effective at inducing behaviour change than the provision of information alone . We hypothesize that research recruitment , baseline self- assessment and contact with study personnel are influences that induce positive reactive effects on stimulant use Encouraging but limited research indicates that brief motivational interventions may be an effective way to reduce heavy episodic drinking in college students . At 2 campuses , students ( 83 % male ) m and ated to a substance use prevention program were r and omly assigned to 1 of 2 individually administered conditions : ( a ) a brief motivational interview ( BMI ; n = 34 ) or ( b ) an alcohol education session ( AE ; n = 30 ) . Students in the BMI condition reported fewer alcohol-related problems than the AE students at 3- and 6-month assessment s. Trends toward reductions in number of binge drinking episodes and typical blood alcohol levels were seen in both groups . Process measures confirmed the integrity of both interventions . The findings demonstrate that m and ated BMI s can reduce alcohol problems in students referred for alcohol violations OBJECTIVE The aim of this study was to test the efficacy of brief physician advice in reducing alcohol use and related harm in college students . METHOD The College Health Intervention Projects ( CHIPs ) is a r and omized , controlled clinical trial with 12-month follow-up conducted in five college health clinics in Wisconsin ; Washington state ; and Vancouver , Canada . Of the 12,900 students screened for high-risk drinking , 484 men and 502 women met inclusion criteria and were r and omized into a control ( n = 493 ) or intervention ( n = 493 ) group . Ninety-six percent of students participated in the follow-up procedures . The intervention consisted of two 15-minute counseling visits and two follow-up phone calls , and used motivational interviewing , contracting , diary cards , and take-home exercises . RESULTS No significant differences were found between groups at baseline on alcohol use , age , socioeconomic or smoking status , rates of depression , or measures of alcohol-related harm . At 12 months , the experimental subjects reduced their 28-day drinking totals by 27.2 % , and the control group reduced their totals by 21 % . A mixed effects repeated measures model found a statistical difference in favor of the brief-intervention group ( beta = 4.7 , SE = 2.0 , p = .018 ) in 28-day drinking totals . The total Rutgers Alcohol Problem Index score was also significantly different during the 12-month follow-up period ( beta = 0.8 , SE = 0.4 , p = .033 ) . There was no difference on the other outcome measures of interest , such as frequency of excessive heavy drinking , health care utilization , injuries , drunk driving , depression , or tobacco use . CONCLUSIONS The study supports re source allocation and implementation of alcohol screening and brief physician advice in primary care-based college health clinics AIM To evaluate the effectiveness of a brief motivational intervention on alcohol consumption and misuse in young males with alcohol-related face injury . DESIGN R and omized controlled trial . SETTING Oral and maxillofacial surgery out-patient clinic in an urban teaching hospital . PARTICIPANTS One hundred and fifty-one participants were r and omized to motivational intervention and control conditions . INTERVENTIONS Control was treatment as usual . The intervention was treatment as usual plus a one-session brief motivational intervention administered by a nurse . MEASUREMENTS Three sets of measurements were taken at baseline , 3-month and 1-year follow-up . Collateral measurements were also taken at 1-year follow-up . Primary outcome measures were total alcohol consumption , typical weeks consumption and days abstinent in preceding 3 months . Other outcome measures included the Alcohol Use Disorders Identification Test , a short form of the Alcohol Problems Question naire , and a measure of satisfaction with social relationships . RESULTS There was a significant decrease in 84-day total alcohol consumption across the year ( P < 0.006 ) and further , a significant effect for the motivational intervention was demonstrated ( P < 0.029 ) . This pattern was repeated for days abstinent and alcohol consumption in a typical week as well as alcohol-related problems . There was a significantly greater reduction in the percentage of hazardous drinkers in the motivational intervention group ( from 60 % to 27 % , P < 0.009 ) compared to the control group ( from 54 % to 51 % , NS ) . CONCLUSION A proportion of young men change their alcohol consumption following alcohol-related injury . A nurse-led psychological intervention adds significantly to the proportion and magnitude of response In this r and omized controlled trial , the authors evaluated brief motivational interventions ( BMI s ) for at-risk college drinkers . Heavy drinking students ( N = 509 ; 65 % women , 35 % men ) were r and omized into 1 of 6 intervention conditions formed by crossing the baseline Timeline Followback ( TLFB ) interview ( present versus absent ) and intervention type ( basic BMI , BMI enhanced with a decisional balance module , or none ) . Assessment s completed at baseline , 1 , 6 , and 12 months measured typical and risky drinking as well as drinking-related problems . Relative to controls , the TLFB interview reduced consumption but not problems at 1 month . The basic BMI improved all drinking outcomes beyond the effects of the TLFB interview at 1 month , whereas the enhanced BMI did not . Risk reduction achieved by brief interventions maintained throughout the follow-up year The current study examined the impact of a brief motivational interviewing ( MI ) intervention ( Project CHAT ) on alcohol consumption and drug use for high-risk teens in a primary care clinic that provides health care for underserved population s. Youth ( N=42 , 48 % male ) were screened , and those eligible completed a baseline survey . Baseline survey completers were r and omly assigned to usual care or to an MI intervention and completed a 3-month follow-up survey . The sample ( age 12 to 18 years ) was 85.7 % Hispanic or Latino , 9.5 % African American , and 4.8 % White . At the 3-month follow-up , Project CHAT teens reported less marijuana use , lower perceived prevalence of marijuana use , fewer friends who used marijuana , and lower intentions to use marijuana in the next 6 months , as compared to teens assigned to usual care . Providing this type of brief intervention is a viable approach to working with high-risk teens to decrease substance use This study assessed the impact of a motiv ational interv iewing ( MI ) brief alcohol interv ention and prior v ictimization on alcohol-inv olv ed sexual v ictimization experiences . First-year female college students ( N = 229 ) were r and omly assigned to an interv ention condition : MI , MI with feedback ( MIFB ) , feedback ( FB ) , and assessment only ( AO ) . Findings indicate reduced alcohol use for all conditions and v iolence for MIFB , with interactions for prior v ictimization . The mechanism of change for reduced v ictimization was not reductions in alcohol use and mechanisms for this effectiv eness remain somewhat conv oluted . Tailoring of brief interv entions addressing alcohol use and sexual v iolence , particularly for women with prior v ictimization , is critical Motivational interviewing ( MI ) has been found to be an effective treatment for substance using population s , including incarcerated adolescents . Although some studies suggest MI is more successful with individuals from minority background s , the research remains mixed . The current study investigated the impact of ethnicity on treatment in reducing alcohol and marijuana use among incarcerated adolescents . Adolescents ( 14 - 19 years of age ) were recruited from a state juvenile correctional facility and r and omly assigned to receive MI or relaxation therapy ( RT ) ( N=147 ; 48 White , 51 Hispanic , and 48 African American ; 126 male ; 21 female ) . Interviews were conducted at admission to the facility and 3 months after release . Results suggest that the effects of MI on treatment outcomes are moderated by ethnicity . Hispanic adolescents who received MI significantly decreased total number of drinks on heavy drinking days ( NDHD ) and percentage of heavy drinking days ( PHDD ) as compared to Hispanic adolescents who received RT . These findings suggest that MI is an efficacious treatment for an ethnic minority juvenile justice-involved population in need of evidence -based treatments CONTEXT Emergency department ( ED ) visits present an opportunity to deliver brief interventions to reduce violence and alcohol misuse among urban adolescents at risk of future injury . OBJECTIVE To determine the efficacy of brief interventions addressing violence and alcohol use among adolescents presenting to an urban ED . DESIGN , SETTING , AND PARTICIPANTS Between September 2006 and September 2009 , 3338 patients aged 14 to 18 years presenting to a level I ED in Flint , Michigan , between 12 pm and 11 pm 7 days a week completed a computerized survey ( 43.5 % male ; 55.9 % African American ) . Adolescents reporting past-year alcohol use and aggression were enrolled in a r and omized controlled trial ( SafERteens ) . INTERVENTION All patients underwent a computerized baseline assessment and were r and omized to a control group that received a brochure ( n = 235 ) or a 35-minute brief intervention delivered by either a computer ( n = 237 ) or therapist ( n = 254 ) in the ED , with follow-up assessment s at 3 and 6 months . Combining motivational interviewing with skills training , the brief intervention for violence and alcohol included review of goals , tailored feedback , decisional balance exercise , role plays , and referrals . MAIN OUTCOME MEASURES Self-report measures included peer aggression and violence , violence consequences , alcohol use , binge drinking , and alcohol consequences . RESULTS About 25 % ( n = 829 ) of screened patients had positive results for both alcohol and violence ; 726 were r and omized . Compared with controls , participants in the therapist intervention showed self-reported reductions in the occurrence of peer aggression ( therapist , -34.3 % ; control , -16.4 % ; relative risk [ RR ] , 0.74 ; 95 % confidence interval [ CI ] , 0.61 - 0.90 ) , experience of peer violence ( therapist , -10.4 % ; control , + 4.7 % ; RR , 0.70 ; 95 % CI , 0.52 - 0.95 ) , and violence consequences ( therapist , -30.4 % ; control , -13.0 % ; RR , 0.76 ; 95 % CI , 0.64 - 0.90 ) at 3 months . At 6 months , participants in the therapist intervention showed self-reported reductions in alcohol consequences ( therapist , -32.2 % ; control , -17.7 % ; odds ratio , 0.56 ; 95 % CI , 0.34 - 0.91 ) compared with controls ; participants in the computer intervention also showed self-reported reductions in alcohol consequences ( computer , -29.1 % ; control , -17.7 % ; odds ratio , 0.57 ; 95 % CI , 0.34 - 0.95 ) . CONCLUSION Among adolescents identified in the ED with self-reported alcohol use and aggression , a brief intervention result ed in a decrease in the prevalence of self-reported aggression and alcohol consequences . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00251212 OBJECTIVE The aim of this research was to study marijuana use , associated risks , and response to brief motivational intervention among young adult drinkers treated in an emergency department . METHOD Study participants ( N = 215 ; ages 18 - 24 ) were in a r and omized controlled trial for alcohol use that compared motivational interviewing with personalized feedback ( MI ) with personalized feedback only . Past-month marijuana users were compared with nonusers on demographics , readiness , self-efficacy , and behavioral risk variables . Marijuana use was examined as a potential moderator of alcohol outcomes . Whether marijuana use alone or combined marijuana and alcohol use would be reduced as a result of brief intervention for alcohol was examined at 6 and 12 months . RESULTS Current marijuana users were younger , were more likely to be white , and reported more alcohol use , other illicit drug use , and more alcohol-related consequences than nonmarijuana users . Marijuana use at baseline did not moderate response to brief alcohol treatment . Marijuana use declined from baseline to 6 months for both treatment groups , but only MI participants continued to reduce their use of marijuana from 6- to 12-month follow-up . Reductions in number of days of use of marijuana with alcohol appeared to be primarily a function of decreased alcohol use . CONCLUSIONS Young adult drinkers reporting current marijuana use are at generally higher risk but responded to brief alcohol treatment by reducing alcohol and marijuana use AIMS College students who violate alcohol policies are often m and ated to participate in alcohol-related interventions . This study investigated ( i ) whether such interventions reduced drinking beyond the sanction alone , ( ii ) whether a brief motivational intervention ( BMI ) was more efficacious than two computer-delivered interventions ( CDIs ) and ( iii ) whether intervention response differed by gender . DESIGN R and omized controlled trial with four conditions [ brief motivation interventions ( BMI ) , Alcohol 101 Plus ™ , Alcohol Edu for Sanctions ( ® ) , delayed control ] and four assessment s ( baseline , 1 , 6 and 12 months ) . SETTING Private residential university in the United States . PARTICIPANTS Students ( n = 677 ; 64 % male ) who had violated campus alcohol policies and were sanctioned to participate in a risk reduction program . MEASUREMENTS Consumption ( drinks per heaviest and typical week , heavy drinking frequency , peak and typical blood alcohol concentration ) , alcohol problems and recidivism . FINDINGS Piecewise latent growth models characterized short-term ( 1-month ) and longer-term ( 1 - 12 months ) change . Female but not male students reduced drinking and problems in the control condition . Males reduced drinking and problems after all interventions relative to control , but did not maintain these gains . Females reduced drinking to a greater extent after a BMI than after either CDI , and maintained reductions relative to baseline across the follow-up year . No differences in recidivism were found . CONCLUSIONS Male and female students responded differently to sanctions for alcohol violations and to risk reduction interventions . BMI s optimized outcomes for both genders . Male students improved after all interventions , but female students improved less after CDIs than after BMI . Intervention effects decayed over time , especially for males This study piloted a brief individual motivational intervention targeting multiple health risk behaviors in HIV-positive youth aged 16 - 25 . Interviews about sexual behavior and substance use and viral load testing were obtained from 51 HIV-positive youth at baseline and post intervention . Youth were r and omized to receive a four-session motivational enhancement intervention ( N = 25 ) or to a wait-list control ( N = 26 ) . Of the eligible youth approached , 88 % agreed to participate , and 80 % percent of participants completed at least three of four sessions . The treatment group showed significantly greater reductions in unprotected sex acts and in viral load compared with controls . Although change scores for substance use were not significantly different between the two groups , paired t tests demonstrated that reductions in alcohol use and marijuana use were significant for the treatment group at the trend level . There were no significant differences in substance use from baseline to posttest for the control group . Findings demonstrate the potential of a brief motivational enhancement intervention to improve health risk behaviors in HIV-positive youth . Larger r and omized clinical trials are warranted . Re sources required for retention should not be underestimated BACKGROUND R and omized trial evidence on the effectiveness of incarceration and treatment of first-time driving while intoxicated ( DWI ) offenders who are primarily American Indian has yet to be reported in the literature on DWI prevention . Further , research has confirmed the association of antisocial personality disorder ( ASPD ) with problems with alcohol including DWI . METHODS A r and omized clinical trial was conducted , in conjunction with 28 days of incarceration , of a treatment program incorporating motivational interviewing principles for first-time DWI offenders . The sample of 305 offenders including 52 diagnosed as ASPD by the Diagnostic Interview Schedule were assessed before assignment to conditions and at 6 , 12 , and 24 months after discharge . Self-reported frequency of drinking and driving as well as various measures of drinking over the preceding 90 days were available at all assessment s for 244 participants . Further , DWI rearrest data for 274 participants were available for analysis . RESULTS Participants r and omized to receive the first offender incarceration and treatment program reported greater reductions in alcohol consumption from baseline levels when compared with participants who were only incarcerated . Antisocial personality disorder participants reported heavier and more frequent drinking but showed significantly greater declines in drinking from intake to posttreatment assessment s. Further , the treatment result ed in larger effects relative to the control on ASPD than non-ASPD participants . CONCLUSIONS Nonconfrontational treatment may significantly enhance outcomes for DWI offenders with ASPD when delivered in an incarcerated setting , and in the present study , such effects were found in a primarily American-Indian sample Research indicates that motivational enhancement therapy ( MET ) helps catalyze reductions in problem drinking among emerging adults . However , moderators of this intervention remain relatively unknown . Therefore , the objectives of this study were : ( 1 ) to test whether a single session of MET increased motivation to reduce drinking and drinking outcomes ; and ( 2 ) to examine whether genetic dopamine D4 receptor L ( DRD4 L ) and individual personality risk factors ( impulsivity and novelty seeking ) moderated the effects of the MET . These hypotheses were evaluated by r and omly assigning a sample of emerging adult problem drinkers ( n = 67 ) to receive a single session of MET or alcohol education . Follow‐up data indicated that only individuals who were low in impulsivity , novelty seeking and /or who had the short DRD4 variable number of t and em repeats genotype evidence d differentially increased behavior change ( taking steps toward reducing drinking ) following the MET Motivational Interviewing ( MI ) to reduce alcohol and marijuana-related driving events among incarcerated adolescents was evaluated . Adolescents were r and omly assigned to receive MI or Relaxation Training . Follow-up assessment showed that , as compared to RT , adolescents who received MI had lower rates of drinking and driving , and being a passenger in a car with someone who had been drinking . Effects were moderated by levels of depression . At low levels of depression , MI evidence d lower rates of these behaviors ; at high levels of depression , effects for MI and RT were equivalent . Similar patterns were found for marijuana-related risky driving , but effects were non-significant AIM To test the effectiveness of motivational interviewing ( MI ) in comparison with drug information and advice in opportunistically securing reductions in drug-related risk among young cannabis users not seeking help . DESIGN R and omized controlled trial . SETTING Eleven London Further Education colleges . PARTICIPANTS A total of 326 students aged 16 - 19 years who smoked cannabis weekly or more frequently . INTERVENTIONS Participants were r and omized to a single-session intervention of MI or drug information and advice-giving . MEASUREMENTS Cannabis use , cigarette smoking and alcohol consumption and harm outcomes were assessed after both 3 and 6 months . FINDINGS No differences were found between MI and drug information and advice , although MI fidelity was not high . There were wide-ranging individual practitioner effects on observed outcomes and a practitioner-intervention interaction was detected in relation to cannabis cessation after 3 months . Change over time was more pronounced for cannabis use than for other drug use . CONCLUSIONS Further study of the nature and consequences of MI fidelity , and individual practitioner effects more generally , is needed . Advice may be an effective brief intervention with young cannabis users in its own right and should be evaluated further in trials BACKGROUND Brief motivational intervention ( BMI ) is one of the few effective strategies targeting alcohol consumption , but has not been tested in young men in the community . We evaluated the efficacy of BMI in reducing alcohol use and related problems among binge drinkers and in maintaining low-risk drinking among non-bingers . METHODS A r and om sample of a census of men included during army conscription ( which is m and atory for 20-year-old males in Switzerl and ) was r and omized to receive a single face-to-face BMI session ( N=199 ) or no intervention ( N=219 ) . A six-month follow-up rate was obtained for 88.7 % of the subjects . RESULTS Among binge drinkers , there was 20 % less drinking in the BMI group versus the control group ( incidence rate ratio=0.80 , confidence interval 0.66 - 0.98 , p=0.03 ) ; the BMI group showed a weekly reduction of 1.5 drinks compared to an increase of 0.8 drinks weekly in the control group . Among subjects who experienced one or more alcohol-related consequences over the last 12 months , there was 19 % less drinking in the BMI group compared to the control group ( incidence rate ratio=0.81 , confidence interval 0.67 - 0.97 , p=0.04 ) . Among non-bingers , BMI did not contribute to the maintenance of low-risk drinking . CONCLUSION BMI reduced the alcohol use of binge drinkers , particularly among those who experienced certain alcohol-related adverse consequences . No preventive effect of BMI was observed among non-bingers . BMI is a plausible secondary preventive option for young binge drinkers |
2,279 | 30,328,311 | Significant differences were observed in enamel demineralization between laser-irradiated and control groups for all laser types : argon laser , CO2 laser , neodymium-doped yttrium aluminum garnet ( Nd : YAG ) laser , and Optodan ® laser , except for argon laser application for curing bracket adhesives , where no statistically significant differences were noted . | The objective of this study was to investigate the in vivo effectiveness of laser in the prevention of enamel demineralization during orthodontic treatment . | The aim of this in vitro was to evaluate the effects of tricalcium phosphate ( TCP ) and amorphous calcium phosphate ( ACP ) containing varnish material s and Er : YAG laser irradiation on enamel demineralization around orthodontic brackets . Forty extracted human premolar teeth were r and omly divided into four treatment groups ( i.e. , 10 in each group ) : ( 1 ) 5 % NaF-ACP varnish , ( 2 ) 5 % NaF-TCP varnish , ( 3 ) Er : YAG laser , and ( 4 ) control ( no treatment ) . Er : YAG laser was operated at a wavelength of 2.94 μm and the energy output was 80 mJ per pulse ; a pulse duration of 200 μsec and and a frequency of 2 Hz were used with water cooling . All sample s were then put into pH cycles . Surface microhardness values and representative SEM images were assessed . Surface microhardness values were evaluated using Kruskal-Wallis and Mann-Whitney U tests . The results revealed that demineralization was significantly lower in the TCP and ACP varnish groups , whereas mean surface microhardness values of the TCP varnish were found higher than the ACP ( P < 0.05 ) . TCP and ACP varnish material s were found effective for reducing enamel demineralization around orthodontic brackets . Use of Er : YAG laser irradiation as described in this study for inhibition of demineralization was found not satisfactory OBJECTIVE This clinical pilot study was conducted to investigate the effectiveness of argon laser irradiation to reduce demineralization or loss of tooth structure in vivo . SUMMARY BACKGROUND DATA In vitro research previously demonstrated the ability of argon laser irradiation to reduce demineralization or loss of tooth structure . METHODS Using the Ogaard model of producing demineralization , the experimental teeth were irradiated with argon laser of 250 mW ( producing approximately 12 J/cm2 ) prior to b and ing . Polarized light evaluation of the sectioned , extracted teeth was used to determine the amount of demineralization . RESULTS Results showed a 29.1 % reduction in demineralization in the experimental teeth as compared to the bilateral control teeth . CONCLUSION Low-power argon laser irradiation significantly reduced demineralization clinical ly 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 A prospect i ve clinical trial was carried out to compare argon laser-curing of a traditional light-activated composite resin with conventional visible light-curing in terms of bond failure rate and incidence of enamel decalcification . Forty-five patients with a total of 742 metal brackets bonded to the upper and /or lower teeth in a modified split-mouth design participated in the study . The adhesive ( Transbond XT ) on the control teeth was cured by conventional visible light for 40 seconds , and the experimental teeth were exposed to 10 seconds of 250 mW argon laser irradiation . The patients were monitored for a period of 14 months . Intraoral photographic slides of the maxillary anterior teeth ( 212 in total ) were taken at the beginning of treatment , after 12 months of treatment , following application of a plaque disclosing agent , and at the end of the observation period , following temporary debonding . Seven dentists used st and ardized rating systems to evaluate decalcification and plaque accumulation . The results of this study indicated that there were no significant differences between curing methods for the incidence of decalcification and plaque accumulation . However , the 10 second argon laser-curing method showed a statistically lower bond failure rate ( 2.4 per cent , P < 0.05 ) than the 40 second conventional visible light-curing method ( 5.7 per cent ) . It is concluded that the use of argon laser curing is superior to that of conventional light-curing with respect to bond failure and chairside time . However , the incidence of decalcification seems to be similar Objective This study was design ed to evaluate the effect of argon laser irradiation on development and progress of enamel demineralization around orthodontic brackets . Material s and Methods : Fifty caries-free , intact human premolars were r and omly assigned to one of the following five equal groups : Groups 1 ( control ) and 2 : The brackets were bonded using conventional halogen light for 40s and argon laser for 10s , respectively . Teeth in group 3 were lased with argon laser for 10s before bracket bonding with halogen light . Group 4 was the same as group 3 except that brackets were also bonded with argon laser . In group 5 sample s were bonded conventionally , immersed in an artificial caries solution for two days and then irradiated for 10s with argon laser . All sample s were subjected to demineralization by artificial caries solution for 10 days . After bracket removal , sample s were buccolingually sectioned and evaluated by polarized light microscopy . Decalcified lesion depth in each section was measured by a trained examiner in a blind fashion . Data were analyzed in SPSS 14 using one-way ANOVA and Tukey ’s HSD post hoc test . Results : The control group showed the greatest mean lesion depth while group 5 revealed the lowest . The laser-treated groups had significantly lower mean lesion depth compared with the control group ( P<0.05 ) except for group 4 ( P=0.192 ) . Conclusion : Argon laser irradiation for 10s before or during bracket bonding can increase caries resistance of intact and demineralized enamel Plaque control during the course of orthodontic treatment is not an easy task , and dental caries are not an unlikely complication . We examined the possibility of controlling dental caries with Nd-YAG laser irradiation in orthodontic patients . As a preliminary experiment , we used the Nd-YAG laser to irradiate an extracted tooth and then left it to soak in lactic acid . The decay of the tooth was evaluated with a scanning electron microscope ( SEM ) ; tooth decay was inhibited by the action of the laser . Twenty patients undergoing orthodontic treatment for early decalcification of the teeth ( white spot lesions ) were selected , and photographs were taken of their oral cavities . White spot lesions on the four incisors and two canines of the maxilla were traced on tracing paper , and their areas were calculated by computer . Ten of the patients received laser treatment and acidulated phosphate fluoride solution ( APF ) ; the other ten acted as the control group . Between 11 and 12 months later , we photographed the oral cavity as we had previously ; the white spot lesions were again traced and their areas calculated . The changes in the areas of the white spots of the laser-irradiated and control groups showed the following increases : laser-irradiated group , 1.41 times ; controls , 2.87 times . The difference was statistically significant . These results demonstrate that Nd-YAG laser irradiation with application of APF acts as an effective method of caries control during orthodontic treatment Enamel decalcification is a significant problem in orthodontic patients . The argon laser has been shown to reduce decalcification during an acidic challenge in vitro . The purpose of this study was to investigate the in vivo effects of argon laser irradiation on enamel decalcification during orthodontic treatment . Nine volunteers whose treatment plans included 4 first premolar extraction s were enrolled in the study . The 36 extracted premolars were assigned to 1 of the following 4 groups : group 1 , control group with no treatment ; group 2 ( pumice-laser ) , teeth were pumiced for 3 seconds and treated with a 325 mW , 5-mm diameter laser beam for 60 seconds ; group 3 ( pumice-etch-laser ) , teeth were pumiced for 3 seconds , acid-etched with 30 % phosphoric acid for 30 seconds , and treated for 60 seconds with laser ; and group 4 ( laser only ) , teeth were treated for 60 seconds with laser . A specially design ed ( oversized ) orthodontic b and was fitted on each of the premolars to create a pocket for decalcification . The b and s were cemented in place for 5 weeks . After extraction , the teeth were sectioned and examined under polarized light microscopy . Images of lesions were digitally analyzed and measured . Average lesion depths were calculated from 3 depth measurements recorded 10 microm apart . Average lesion area was calculated with the aid of imaging analysis software . Data were analyzed with analysis of variance ( P < .05 ) and Student t tests . Significant differences were found in lesion depth ( P < .001 ) and lesion area ( P < .01 ) among the 4 test groups . The average lesion depths were 15.93 + /- 9.31 microm ( control ) , 6.45 + /- 8.70 microm ( pumice-laser ) , 1.71 + /- 4.82 microm ( pumice-etch-laser ) , and 1.34 + /- 3.80 microm ( laser only ) . The average lesion areas were 1028.67 + /- 725.68 microm ( 2 ) ( control ) , 555.49 + /- 948.20 microm ( 2 ) ( pumice-laser ) , 79.91 + /- 226.03 microm ( 2 ) ( pumice-etch-laser ) , and 55.71 + /- 157.59 microm ( 2 ) ( laser only ) . The average lesion depth in the laser-only group was reduced by 94.1 % and the average lesion area was reduced by 94.4 % when compared with the control group . In the pumice-etch-laser group , the average lesion depth was reduced by 89.1 % and the average lesion area was reduced by 92.2 % when compared with the control group . There were no significant differences in lesion depth and lesion area between maxillary and m and ibular teeth ( P < .06 and P < .08 , respectively ) and between the teeth on the right and left sides ( P < .68 and P < .55 , respectively ) . These results show that argon laser irradiation is effective in reducing enamel decalcification during orthodontic treatment . Pumicing and etching do not appear to reduce the effect of laser on enamel solubility Argon lasers , because of their significant timesavings over conventional curing lights , have been investigated for use in bonding orthodontic brackets . They are also being investigated for their ability to confer demineralization resistance on enamel , which is of great interest in orthodontics . A two-part in vitro study on 86 human posterior teeth was conducted to determine the effects of a five-second argon laser exposure on shear bond strength and to evaluate the effects of a five- and 10-second argon laser exposure ( 250 mW ) on demineralization of enamel surrounding orthodontic brackets after exposure to an artificial caries bath . Brackets cured with the argon laser for five seconds yielded mean bond strengths similar to those attained with a 40-second conventional light-cured control ( n = 13 per group , 20.4 vs 17.8 MPa ) . Brackets cured with the argon laser for 10 seconds result ed in significantly lower mean lesion depth when compared with a visible light control ( n = 20 per group , 107.8 vs 137.2 microm , P = .038 ) . There were no statistically significant differences in lesion depth between the five-second argon laser and the visible light control groups . Overall , there was a 15 % and 22 % reduction in lesion depths for the five- and 10-second group , respectively . Poor correlations were found between the clinical appearance of decalcifications and their lesion depth . Argon lasers used for bonding orthodontic brackets would save a significant amount of chair time while possibly conferring demineralization resistance upon the enamel Introduction : The aim of this study was to assess the caries-preventive potential of carbon dioxide ( CO2 ) laser application in conjunction with the use of titanium tetra fluoride solution on the enamel adjacent to bracket . Methods : Seventy-five freshly extracted bovine incisors were used . In order to attach the brackets , the area of examination was covered with adhesive tape to limit acid etching of the entire enamel surface . Metal orthodontic brackets for upper central were bonded to all the teeth following the manufacturer 's instruction . Then all the teeth were painted with 2 layers of acid-resistant nail varnish on all surfaces except the boxes area cervical to the brackets . The teeth were then r and omly divided into five groups ( n = 15 ) : control group ( C ) ; laser group ( L ) ; titanium group ( T ) ; laser-titanium group ( LT ) and titanium-laser group ( TL ) . The laser-titanium group was first irradiated with CO2 laser ( same as the L group ) then TiF4 solution was applied on the enamel ( same as the T group ) . Sample s in the TL group were first treated with TiF4 solution ( same as the T group ) and then irradiated with CO2 laser on the surface ( same as the L group ) . Then , the teeth were immersed in pH-cycling solutions . After that , the amount of calcium released into the two solutions ( de- and re-mineralization ) was measured with an atomic absorption spectroscopy . The data were analyzed by one-way Analysis of var-iance ( ANOVA ) and Tukey test . Results : Calcium loss in LT , TL and T groups were significantly lower than those in the L and C groups ( P < 0.05 ) . Conclusion : The application of Titanium tetra fluoride 4 % solution on enamel can inhibit as much as 87 % of subsequent caries like lesion progression OBJECTIVE This in vivo pilot study investigated the role of argon laser irradiation and combined fluoride and argon laser treatment in accelerated natural caries development in sound enamel surfaces beneath plaque-retentive orthodontic b and s. METHOD AND MATERIAL S Five patients ( 3 female , 2 male , ages 19 to 28 years ) requiring tooth extraction prior to orthodontic treatment , participated in the study . Buccal surfaces were treated with either : ( 1 ) argon laser ( 250 mW for 10 seconds , ARGO-MOD ) ; ( 2 ) topical fluoride ( 0.5 % fluoride ion , Thera-Flur-N ) followed by argon lasing ; or ( 3 ) no treatment ( control ) . Orthodontic b and s with plaque-retentive slots on buccal surfaces were placed on the teeth slated for extraction ( n = 14 ) . Following a minimum of 5 weeks of intraoral exposure , the teeth were extracted for laboratory analysis . The teeth underwent serial longitudinal sectioning ( 12 sections per tooth ) . The sections were imbibed in water , and lesion depths were determined with each section , using polarized light microscopy . Comparisons were made among treatment groups ( analysis of variance , Duncan 's multiple range test for paired sample s ) . RESULTS Mean lesion depths were : 261 + /- 24 microm for the no treatment control group ( n = 84 sections ) ; 147 + /- 18 microm for the argon laser group ( n = 24 sections ) ; and 99 + /- 12 microm for the fluoride and argon laser group ( n = 60 sections ) . Both the argon laser ( 44 % ) and the fluoride and argon laser groups ( 62 % ) had significant lesion depth reductions compared to controls . The addition of fluoride treatment prior to argon lasing result ed in a 32 % reduction in lesion depth compared to argon laser treatment alone . CONCLUSIONS Within this clinical pilot study , in vivo natural caries formation was affected significantly by a single exposure to low fluence argon laser irradiation . Topical fluoride treatment in combination with argon lasing provided an even greater degree of resistance against in vivo enamel caries development . A simple technique for reducing the caries susceptibility of enamel may be a clinical reality |
2,280 | 31,102,111 | Inconsistent results were found for both peak vertical ground reaction force and impact forces after ACL-R. Patellofemoral and tibiofemoral joint contact forces differed from both contralateral or control limbs up until at least 2.5 years after ACL-R and moderate evidence indicated no difference for muscle activations during moderate speed running .
Quadriceps and hamstring strength asymmetries , and knee function , but not surgical techniques , were likely to be associated with both knee kinematics and kinetics during running after ACL-R. Conclusion After ACL-R , knee flexion motion and internal knee extension moment are the most affected variables and are consistently smaller in the injured limb during running when pooling evidence .
Clinicians should be aware that these deficits do not appear to resolve with time and , thus , specific clinical interventions may be needed to reduce long-term disability . | Background A return to running after anterior cruciate ligament reconstruction ( ACL-R ) is critical to the clinical success of any cutting and pivoting athlete who wishes to return to sport .
Knowledge of specific alterations during running after ACL-R is required to optimise rehabilitation for improving outcomes and long-term disability .
Objective The objective of this systematic review was to summarise kinematic , kinetic and muscle activation data during running after ACL-R and the intrinsic factors ( e.g. surgical technique and strength asymmetries ) affecting running biomechanics . | Background The effectiveness of anterior cruciate ligament reconstruction for restoring normal knee kinematics is largely unknown , particularly during sports movements generating large , rapidly applied forces . Hypothesis Under dynamic in vivo loading , significant differences in 3-dimensional kinematics exist between anterior cruciate ligament-reconstructed knees and the contralateral , uninjured knees . Study Design Prospect i ve , in vivo laboratory study . Methods Kinematics of anterior cruciate ligament-reconstructed and contralateral ( uninjured ) knees were evaluated for 6 subjects during downhill running 4 to 12 months after anterior cruciate ligament reconstruction , using a 250 frame/s stereoradiographic system . Anatomical reference axes were determined from computed tomography scans . Kinematic differences between the uninjured and reconstructed limbs were evaluated with a repeated- measures analysis of variance . Results Anterior tibial translation was similar for the reconstructed and uninjured limbs . However , reconstructed knees were more externally rotated on average by 3.8 ± 2.3 ° across all subjects and time points ( P = .0011 ) . Reconstructed knees were also more adducted , by an average of 2.8 ± 1.6 ° ( P = .0091 ) . Although differences were small , they were consistent in all subjects . Conclusions Anterior cruciate ligament reconstruction failed to restore normal rotational knee kinematics during dynamic loading . Clinical Relevance Although further study is required , these abnormal motions may contribute to long-term joint degeneration associated with anterior cruciate ligament injury/reconstruction Background : Limited knee flexion and increased muscle co-contraction during jump l and ing are believed to diminish outcomes after anterior cruciate ligament ( ACL ) reconstruction . The efficacy of jump training to improve patients ’ mechanical and neuromuscular deficits is understudied . Hypothesis : Jump training will improve functional , mechanical , and neuromuscular outcomes and higher repetition training augmented by body weight support will result in better retention of gains . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Thirty athletes ( 18 months after surgery ) were screened , and 19 with mechanical deficits and limited clinical outcomes were enrolled in the trial . Testing included the International Knee Documentation Committee ( IKDC ) question naire , leg l and ing mechanics via motion analysis , knee joint effusion using a stroke test , and a surface electromyography – generated co-contraction index during a single-legged l and ing . Participants were r and omly assigned to 1 of 2 groups : jump training with normal body weight ( JTBW ) and high-repetition jump training with body weight support ( JTBWS ) . Knee effusion grading throughout training was used to assess joint tolerance . Changes in outcomes over time were analyzed with mixed-effects modeling . Immediate outcomes were compared with retention testing at 8 weeks after training by use of 2-way analyses of variance with effects of time and group . Results : Significant effects of time were found during the training phase for all outcome measures , but no effects of group or sex were found . IKDC score ( pooled ; mean ± SD ) increased from 76 ± 12 to 87 ± 8 ( P < .001 ) . Knee flexion during single-legged l and ing increased from 57 ° ± 11 ° to 73 ° ± 9 ° ( P < .001 ) . Average co-contraction index decreased from 37 ± 15 to 19 ± 6 ( P < .001 ) . All measures were retained over the retention period in both groups . The relative risk of knee effusion of the JTBW group versus the JTBWS group was 4.2 ( 95 % CI , 2.25 - 7.71 ; P < .001 ) . Conclusion : Jump training mitigated some risk factors for second injury and osteoarthritis in patients after ACL reconstruction . Training made lasting improvements in physical function measures as well as mechanical and neuromuscular coordination deficits . Higher repetitions used with body weight support did not improve retention but substantially reduced risk for effusion . Clinical Relevance : Jump training is an efficacious intervention for athletes with poor outcomes after ACL reconstruction , and training with body weight support lessens the risk for excessive joint stress during practice . Registration : NCT02148172 ( Clinical Trials.gov identifier Background Knee reinjury after ACL reconstruction is common and increases the risk of osteoarthritis . There is sparse evidence to guide return to sport ( RTS ) decisions in this population . Objectives To assess the relationship between knee reinjury after ACL reconstruction and ( 1 ) return to level I sports , ( 2 ) timing of RTS and ( 3 ) knee function prior to return . Methods 106 patients who participated in pivoting sports participated in this prospect i ve 2-year cohort study . Sports participation and knee reinjury were recorded monthly . Knee function was assessed with the Knee Outcome Survey — Activities of Daily Living Scale , global rating scale of function , and quadriceps strength and hop test symmetry . Pass RTS criteria were defined as scores > 90 on all tests , failure as failing any . Results Patients who returned to level I sports had a 4.32 ( p=0.048 ) times higher reinjury rate than those who did not . The reinjury rate was significantly reduced by 51 % for each month RTS was delayed until 9 months after surgery , after which no further risk reduction was observed . 38.2 % of those who failed RTS criteria suffered reinjuries versus 5.6 % of those who passed ( HR 0.16 , p=0.075 ) . More symmetrical quadriceps strength prior to return significantly reduced the knee reinjury rate . Conclusions Returning to level I sports after ACL reconstruction leads to a more than 4-fold increase in reinjury rates over 2 years . RTS 9 months or later after surgery and more symmetrical quadriceps strength prior to return substantially reduce the reinjury rate Background : It has been hypothesized that quadriceps muscle weakness is directly associated with the onset and progression of posttraumatic osteoarthritis after anterior cruciate ligament ( ACL ) injury and reconstruction ( ACLR ) . This relationship , however , has not been studied with a prospect i ve approach that includes the use of tibiofemoral joint space width difference ( JSW-D ) measurements to characterize the onset of posttraumatic osteoarthritis before the clinical manifestation of the disease . Purpose : To assess the relationship between thigh muscle strength and JSW-D at presurgery baseline and at 1- and 4-year follow-up after ACLR compared with healthy , noninjured participants of similar sex , age , body mass index , and activity level . Study Design : Cohort study ; Level of evidence , 3 . Methods : A total of 39 unilateral ACL-injured patients and 32 healthy controls were followed prospect ively . During each follow-up , JSW , isokinetic knee strength , single-legged hop , and clinical - and patient-oriented outcomes were assessed . At final follow-up , ACL-injured participants who had JSW-D values ( considered as the injured minus normal knee ) that were less than the 95 % confidence interval of controls were considered to be in the ACLR-narrow group , while those with JSW-D values that fell within the confidence intervals were in the ACLR-normal group . Relationships were evaluated between ACLR groups and controls via multilevel regression , as well as Kruskal-Wallis tests for between-group comparisons at 4-year follow-up . Results : At 4-year follow-up , 30 participants ( 79 % ) were in the ACLR-normal group and 8 ( 21 % ) were in the ACLR-narrow group . At baseline , the extension , flexion , and extension/flexion ratio strength values for both ACLR groups were significantly lower than those of controls ( P ≤ .05 ) , while the ACLR-narrow group had significantly lower extension strength at 60 and 180 deg/s ( P = .04 and .03 , respectively ) , as well as extension/flexion ratio at 60 deg/s ( P = .04 ) in comparison with the ACL-normal group . At 4-year follow-up , 60 deg/s extension strength deficits persisted in the ACLR-narrow group compared with controls and ACLR-normal participants ( P = .01 and .04 , respectively ) . Flexion strength at 180 and 300 deg/s was also significantly lower in the ACLR-narrow group compared with ACLR-normal ( P = .02 and .04 , respectively ) , as was single-legged hop distance ( P = .04 ) . Conclusion : Strength deficits present within months after ACL injury and persist through 4 years after ACLR in participants with significantly narrowed JSW-D , compared with ACLR participants with normal JSW-D and controls . This study revealed a significant relationship between quadriceps strength loss that occurred soon after injury and JSW narrowing Purpose Unrealistic patient expectations have been shown to negatively influence patient-reported outcomes in orthopaedic surgery . Knowledge about patient expectations is important to associate preoperative expectations with the reasonable outcome of a specific procedure . The purpose of this study was to prospect ively analyse and to compare patient expectations of primary and revision anterior cruciate ligament reconstruction ( ACLR ) and to assess the factors associated with patient expectations . Methods Preoperative expectations of 181 consecutive patients undergoing ACLR were assessed prospect ively using a 5-item question naire . Primary ACLR ( P-ACLR ) was performed in 133 patients ( 73 % ) , whereas 48 patients ( 27 % ) underwent revision ACLR ( R-ACLR ) . The question naire assessed the expectation of the overall condition of the knee joint , return to sports , instability , pain , and risk of osteoarthritis . Results All patients expected a normal ( 38 % ) or nearly normal ( 62 % ) condition of the knee joint . Return to sports at the same level was expected by 91 % . With regard to instability ( pain ) , no instability ( pain ) independent of the activity level was expected by 77 % ( 58 % ) . No or only a slightly increased risk of the development of osteoarthritis was expected by 98 % . The R-ACLR group showed a significantly lower expectation of the overall condition ( p = 0.001 ) , return to sports ( p < 0.001 ) , and pain ( p = 0.002 ) . No statistically significant difference was found between female and male patients ( n.s . ) . In the P-ACLR group , patients with a history of previous knee surgery showed inferior expectations of return to sports ( p = 0.015 ) and risk of osteoarthritis ( p = 0.011 ) . Age , number of previous knee surgeries , and pre-injury sports level significantly influenced patient expectations . Conclusions Overall , patient expectations of ACL reconstruction are high . Patients undergoing revision ACL reconstruction have lower but still dem and ing expectations . Younger patients , patients without a history of knee surgery , and highly active patients have higher expectations . Explicit patient information about realistic goals of ACL reconstruction seems to be necessary in order to prevent postoperative dissatisfaction despite a successful operation in the surgeons ’ point of view . Level of evidence Prospect i ve case series , Level IV Abstract Purpose To compare the ability of three different anterior cruciate ligament ( ACL ) reconstruction techniques to normalize rotational knee stability 1 year after ACL reconstruction . Two of these techniques are so-called anatomic techniques . Methods Three different ACL reconstruction techniques were tested for their ability to normalize rotational knee stability in a prospect i ve r and omized study . Forty-seven ACL-deficient ( ACLD ) patients were r and omized to transtibial single-bundle ( SB ) , anatomic SB , and double-bundle ACL reconstruction . Three-dimensional motion analysis was performed preoperatively and at 1-year follow-up to evaluate tibial rotation and rotational stiffness . Motion data were captured using an eight-camera motion analysis system . Tibial rotation was determined during walking , running , and a pivoting task . Other outcome parameters were KT-1000 knee laxity measurements and the subjective outcome scores KOOS and IKDC . Results Three-dimensional motion analysis demonstrated that the tibial internal rotation and the rotational stiffness did not differ between the ACL reconstruction techniques during walking , running , and pivoting at 1-year follow-up . Objective knee stability and subjective outcome scores did not differ between the reconstruction groups . Conclusion No significant difference in rotational stability walking , running , and pivoting was seen between anatomic and nonanatomic ACL reconstruction techniques at 1-year follow-up . Level of evidence Therapeutic study , Level OBJECTIVES To examine the effects of 2 gait retraining protocol s on the gait patterns of patients with bone-patellar tendon-bone anterior cruciate ligament ( ACL ) reconstruction . DESIGN R and omized control , repeated- measures design . SETTING Private orthopedic center and research facility . PARTICIPANTS Sixteen patients with bone-patellar tendon-bone ACL reconstruction , r and omly subdivided into 2 groups ( group 1 , n=8 ; group 2 , n=8 ) , and a healthy control group of 8 subjects . INTERVENTION The 16 subjects with ACL reconstruction were r and omly assigned to 2 different gait retraining protocol s over a 6-week training interval : ( 1 ) . a protocol using a predicted stride frequency calculated from the resonant frequency of a force-driven harmonic oscillator ( FDHO ) model or ( 2 ) . a protocol using the preferred stride frequency ( PSF ) . MAIN OUTCOME MEASURES Gait analyses examining the lower-extremity kinematic , kinetic , and energetic gait patterns of each group . RESULTS Gait retraining with the FDHO model showed improvements in lower-extremity positions , hip and knee extensor angular impulse , and work parameters . Gait retraining with the PSF demonstrated no statistical improvements . The FDHO training protocol facilitated a greater midstance knee range of motion ( ROM ) and greater rates of improvement for midstance ROM , hip extensor angular impulse , and concentric hip extensor work . CONCLUSIONS Gait retraining with the resonant frequency of an FDHO model facilitated a greater recovery of gait function compared with training with the PSF BACKGROUND Recreational runners frequently suffer from chronic pathologies . The knee and ankle have been highlighted as common injury sites . Barefoot and barefoot inspired footwear have been cited as treatment modalities for running injuries as opposed to more conventional running shoes . This investigation examined knee and ankle loading in barefoot and barefoot inspired footwear in relation to conventional running shoes . METHOD Thirty recreational male runners underwent 3D running analysis at 4.0m·s(-1 ) . Joint moments , patellofemoral contact force and pressure and Achilles tendon forces were compared between footwear . FINDINGS At the knee the results show that barefoot and barefoot inspired footwear were associated with significant reductions in patellofemoral kinetic parameters . The ankle kinetics indicate that barefoot and barefoot inspired footwear were associated with significant increases in Achilles tendon force compared to conventional shoes . INTERPRETATION Barefoot and barefoot inspired footwear may serve to reduce the incidence of knee injuries in runners although corresponding increases in Achilles tendon loading may induce an injury risk at this tendon Total sagittal knee laxity and postural control in the sagittal and frontal planes were measured in 25 patients at a mean of 36 months ( range , 27 to 44 ) after anterior cruciate ligament reconstruction and in a control group consisting of 20 uninjured age- and activity-matched subjects . Body sway was measured in the sagittal plane on a stable and on a sway-referenced force plate in single-legged stance , double-legged stance , or both , with the eyes open and closed . Postural reactions to perturbations in the sagittal and frontal planes were recorded in the single-legged stance with the eyes open . Total sagittal plane laxity was significantly greater in the anterior cruciate ligament-reconstructed knee ( 11.2 mm ; range , 6 to 15 ) than in the uninjured knee ( 8.9 mm ; range , 6 to 12 ) or in the control group ( 6.0 mm ; range , 5 to 8) . In spite of this , the patients , in comparison with the controls , exhibited normal postural control except in two variables — the reaction time and the latency between the start of force movement to maximal sway in the sagittal plane perturbations . This supports the hypothesis that rehabilitation , with proprioceptive and agility training , is an important component in restoring the functional stability in the anterior cruciate ligament-reconstructed knee Objective To clarify the determinants of dynamic knee stability early after anterior cruciate ligament injury . Study Design Cohort study ( diagnosis ) ; Level of evidence , 1 . Methods Three hundred forty-five consecutive patients who were regular participants in International Knee Documentation Committee level I/II sports before injury and had an acute isolated anterior cruciate ligament injury from the practice of a single orthopaedic surgeon underwent a screening examination including clinical measures , knee laxity , quadriceps strength , hop testing , and patient self-reported knee function a mean of 6 weeks after injury when impairments were resolved . Independent t tests were performed to evaluate differences in quadriceps strength and anterior knee laxity between potential copers and noncopers . Hierarchical regression was performed to determine the influence of quadriceps strength , preinjury activity level , and anterior knee laxity on hop test performance , as well as the influence of timed hop , crossover hop , quadriceps strength , preinjury activity level , and anterior knee laxity on self-assessed global function . Results Neither anterior knee laxity nor quadriceps strength differed between potential copers and noncopers . Quadriceps strength influenced hop test performance more significantly than did preinjury activity level or anterior knee laxity , but the variance accounted for by quadriceps strength was low ( range , 4%–8 % ) . Timed hop performance was the only variable that affected self-assessed global function . Conclusion Traditional surgical decision making based on passive anterior knee laxity and preinjury activity level is not supported by the results , as neither is a good predictor of dynamic knee stability . A battery of clinical tests that capture neuromuscular adaptations , including the timed hop test , may be useful in predicting function and guiding individualized patient management after anterior cruciate ligament injury BACKGROUND The purpose of this study was to determine whether current post-operative rehabilitation protocol s return the strength of the contralateral uninjured limb knee flexors and extensors after an anterior cruciate ligament ( ACL ) reconstruction to those of an uninjured control group . METHODS Subjects with a hamstring tendon ACL reconstruction ( n=12 ) were compared to an active control group ( n=30 ) . Comprehensive bilateral knee flexor and extensor isovelocity strength testing was performed ( five speeds , 5 - 95 degrees , concentric and eccentric contractions ) . FINDINGS After hamstring tendon ACL reconstruction and rehabilitation , bilateral strength normalization ( within 10 % of the contralateral limb ) is achieved by the knee extensors but not the knee flexors . When compared to the uninjured control group , large and statistically significant strength deficits were demonstrated in the knee extensors and knee flexors of both the anterior cruciate ligament reconstructed ( extensors 24.8 % ; flexors 26.8 % ) and the contralateral uninjured ( extensors 21 % ; flexors 13.5 % ) limbs . INTERPRETATION These findings suggest that improvement can be made in knee flexor rehabilitation after ACL reconstruction and limit the validity of the use of a contralateral leg as a rehabilitation endpoint or as a control in the ACL reconstructed population BACKGROUND While there are many opinions about the expected knee function , sports participation , and risk of knee reinjury following nonsurgical treatment of injuries of the anterior cruciate ligament ( ACL ) , there is a lack of knowledge about the clinical course following nonsurgical treatment compared with that after surgical treatment . METHODS This prospect i ve cohort study included 143 patients with an ACL injury . Isokinetic knee extension and flexion strength and patient-reported knee function as recorded on the International Knee Documentation Committee ( IKDC ) 2000 form were collected at baseline , six weeks , and two years . Sports participation was reported monthly for two years with use of an online activity survey . Knee reinjuries were reported at the follow-up evaluations and in a monthly online survey . Repeated analysis of variance ( ANOVA ) , generalized estimating equation ( GEE ) models , and Cox regression analysis were used to analyze group differences in functional outcomes , sports participation , and knee reinjuries , respectively . RESULTS The surgically treated patients ( n = 100 ) were significantly younger , more likely to participate in level-I sports , and less likely to participate in level-II sports prior to injury than the nonsurgically treated patients ( n = 43 ) . There were no significant group-by-time effects on functional outcome . The crude analysis showed that surgically treated patients were more likely to sustain a knee reinjury and to participate in level-I sports in the second year of the follow-up period . After propensity score adjustment , these differences were nonsignificant ; however , the nonsurgically treated patients were significantly more likely to participate in level-II sports during the first year of the follow-up period and in level-III sports over the two years . After two years , 30 % of all patients had an extensor strength deficit , 31 % had a flexor strength deficit , 20 % had patient-reported knee function below the normal range , and 20 % had experienced knee reinjury . CONCLUSIONS There were few differences between the clinical courses following nonsurgical and surgical treatment of ACL injury in this prospect i ve cohort study . Regardless of treatment course , a considerable number of patients did not fully recover following the ACL injury , and future work should focus on improving the outcomes for these patients . LEVEL OF EVIDENCE Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence Background Retention of movement technique is crucial in anterior cruciate ligament ( ACL ) injury prevention programs . It is unknown if specific instructions or video instructions result in changes in kinematic and kinetic measures during a relatively short training session , and in a retention test one week later . Hypothesis/ Purpose The purpose was to determine the effects of verbal external focus ( EF ) , verbal internal focus ( IF ) and video instructions ( VI ) on l and ing technique ( i.e. kinematics and kinetics ) during training and retention . Study Design R and omized Controlled Trial . Methods This study compared verbal EF , verbal IF , VI and CTRL group . Forty healthy athletes were assigned to the IF ( n=10 ) , EF ( n=10 ) , VI ( n=10 ) or CTRL group ( n=10 ) . A jump-l and ing task was performed as a baseline , followed by two training blocks ( TR1 and TR2 ) and a post test . Group specific instructions were offered in TR1 and TR2 . In addition , subjects in the IF , EF and VI groups were free to ask for feedback after every jump in TR1 and TR2 . One week later , a retention test was conducted without specific instructions or feedback . Kinematics and kinetics were captured using an 8-camera motion analysis system . Results Males and females in the EF and VI instruction group showed beneficial results during and after the training session , in terms of improved l and ing technique . Retention was achieved after only a short training session . Conclusion ACL injury prevention programs should include EF and /or VI instructions to improve kinematics and kinetics and achieve retention . Level of Evidence 3b ABSTRACT We evaluated the efficacy of an in-field gait retraining programme using mobile biofeedback to reduce cumulative and peak tibiofemoral loads during running . Thirty runners were r and omised to either a retraining group or control group . Retrainers were asked to increase their step rate by 7.5 % over preferred in response to real-time feedback provided by a wrist mounted running computer for 8 routine in-field runs . An inverse dynamics driven musculoskeletal model estimated total and medial tibiofemoral joint compartment contact forces . Peak and impulse per step total tibiofemoral contact forces were immediately reduced by 7.6 % and 10.6 % , respectively ( P < 0.001 ) . Similarly , medial tibiofemoral compartment peak and impulse per step tibiofemoral contact forces were reduced by 8.2 % and 10.6 % , respectively ( P < 0.001 ) . Interestingly , no changes were found in knee adduction moment measures . Post gait retraining , reductions in medial tibiofemoral compartment peak and impulse per step tibiofemoral contact force were still present ( P < 0.01 ) . At the 1-month post-retraining follow-up , these reductions remained ( P < 0.05 ) . With these per stance reductions in tibiofemoral contact forces in mind , cumulative tibiofemoral contact forces did not change due to the estimated increase in number of steps to run 1 km Background Athletes who return to sport participation after anterior cruciate ligament reconstruction ( ACLR ) have a higher risk of a second anterior cruciate ligament injury ( either reinjury or contralateral injury ) compared with non — anterior cruciate ligament— injured athletes . Hypotheses Prospect i ve measures of neuromuscular control and postural stability after ACLR will predict relative increased risk for a second anterior cruciate ligament injury . Study Design Cohort study ( prognosis ) ; Level of evidence , 2 . Methods Fifty-six athletes underwent a prospect i ve biomechanical screening after ACLR using 3-dimensional motion analysis during a drop vertical jump maneuver and postural stability assessment before return to pivoting and cutting sports . After the initial test session , each subject was followed for 12 months for occurrence of a second anterior cruciate ligament injury . Lower extremity joint kinematics , kinetics , and postural stability were assessed and analyzed . Analysis of variance and logistic regression were used to identify predictors of a second anterior cruciate ligament injury . Results Thirteen athletes suffered a subsequent second anterior cruciate ligament injury . Transverse plane hip kinetics and frontal plane knee kinematics during l and ing , sagittal plane knee moments at l and ing , and deficits in postural stability predicted a second injury in this population ( C statistic = 0.94 ) with excellent sensitivity ( 0.92 ) and specificity ( 0.88 ) . Specific predictive parameters included an increase in total frontal plane ( valgus ) movement , greater asymmetry in internal knee extensor moment at initial contact , and a deficit in single-leg postural stability of the involved limb , as measured by the Biodex stability system . Hip rotation moment independently predicted second anterior cruciate ligament injury ( C = 0.81 ) with high sensitivity ( 0.77 ) and specificity ( 0.81 ) . Conclusion Altered neuromuscular control of the hip and knee during a dynamic l and ing task and postural stability deficits after ACLR are predictors of a second anterior cruciate ligament injury after an athlete is released to return to sport OBJECTIVE To examine the effect of whole-body vibration ( WBV ) on running biomechanics in individuals with anterior cruciate ligament reconstruction ( ACLR ) . DESIGN Single-blind r and omized crossover trial . SETTING Research laboratory . PARTICIPANTS Individuals ( N=20 ) with unilateral ACLR ( age [ ± SD]=22.3 [ ±3.3 ] years ; mass=71.8 [ ±15.3 ] kg ; time since ACLR=44.9 [ ±22.8 ] months ; 15 females , 10 patellar tendon autograft , 7 hamstrings autograft , 3 allograft ; International Knee Documentation Committee Score=83.5 [ ±9.3 ] ) . MAIN OUTCOME MEASURE Participants performed isometric squats while being exposed to WBV or no vibration ( control ) . WBV and control conditions were delivered in a r and omized order during separate visits separated by 1-week washout periods . Running biomechanics of the injured and uninjured limbs were evaluated before and immediately after each intervention . Dependent variables included peak vertical ground reaction force ( GRF ) and loading rate ( LR ) , peak knee flexion angle and external moment , and knee flexion excursion during the stance phase of running . RESULTS There was an increase in knee flexion excursion ( + 4.1 ° , 95 % confidence interval [ CI ] : 0.65 , 7.5 ° ) and a trend toward a reduction in instantaneous LR after WBV in the injured limb ( -4.03 BW/sec-1 , 95 % CI -0.38 , -7.69 ) . No effect was observed on peak GRF , peak knee flexion angle , or peak external knee flexion moment , and no effect was observed in the uninjured limb . CONCLUSIONS Our findings indicate that a single session of WBV acutely increases knee flexion excursion . WBV could be useful to improve running characteristics in individuals with knee pathology |
2,281 | 31,332,983 | Our systematic review showed that positive autologous serum skin test results , positive baseline basophil histamine release assays , positive baseline basophil activation test responses , elevated baseline plasma D-dimer levels , elevated baseline serum interleukin (IL)-2 , IL-5 , and tumor necrosis factor-alpha ( TNF-α ) levels , and low baseline serum IgE levels might assist in predicting favorable CsA responses in CSU patients .
Decreased plasma D-dimer levels ; and decreased serum IL-2 , IL-5 , and TNF-α levels were reported to be correlated with clinical improvement after CsA treatment .
Since most positive results were from non- RCT articles and some data were still inconsistent , this systematic review identified no reliable practical biomarker for predicting CsA treatment response in patients with CSU .
There were no positive predictors with good consistency and mechanical plausibility | PURPOSE This study aim ed to systemically review literature relating to factors that could potentially predict a favorable response to cyclosporine A ( CsA ) treatment for chronic spontaneous urticaria ( CSU ) . | Background Histamine‐releasing activity ( HRA ) is detectable in up to 50 % of patients with chronic ordinary urticaria . Objectives To determine the effect of cyclosporin on clinical features and HRA in patients with chronic urticaria . Methods Thirty patients with severe unremitting disease , responding poorly to antihistamines and showing a positive autologous serum skin test ( ASST ) as a marker of HRA , were r and omized to 4 mg kg−1 daily of cyclosporin ( S and immun ® , n = 20 ) or placebo ( n = 10 ) for 4 weeks . Non‐responders were offered open‐label cyclosporin for 4 weeks . All were followed for up to 20 weeks or until clinical relapse ; all took cetirizine 20 mg daily throughout the study . The primary measure of efficacy was a daily urticaria activity score ( UAS ) of weal numbers and itch ( maximum score 42 per week ) . A positive response was defined as a reduction to < 25 % of baseline weekly UAS and relapse as a return to > 75 % . The effect of cyclosporin on serum HRA was assessed by in vitro basophil histamine release assays and ASSTs before and after treatment . Results Twenty‐nine patients ( 19 active , 10 controls ) completed the r and omized trial medication . Eight of 19 on active treatment but none on placebo had responded at 4 weeks ( P < 0·05 ) . Three others on active drug met the criterion for response at 2 weeks but not at 4 weeks . Mean reduction in UAS between weeks 0 and 4 was 12·7 ( 95 % confidence interval , CI 6·6–18·8 ) for active and 2·3 ( 95 % CI − 3·3–7·9 ) for placebo ( P = 0·005 ) . Seventeen non‐responders ( seven r and omized to active and 10 to placebo ) chose open‐label cyclosporin and 11 responded after 4 weeks . Six of the eight r and omized active drug responders relapsed within 6 weeks . Of the 19 responders to r and omized and open‐label cyclosporin , five ( 26 % ) had not relapsed by the study end‐point . Mean in vitro serum HRA fell from 36 % ( 95 % CI 22–49 % ) to 5 % ( 95 % CI 1–8 % ) after cyclosporin treatment ( n = 11 , P < 0·0001 ) . The ASST response to post‐treatment serum was also reduced ( P < 0·05 ) . Conclusions This study shows that cyclosporin is effective for chronic urticaria and provides further evidence for a role of histamine‐releasing autoantibodies in the pathogenesis of this chronic ‘ idiopathic ’ disease This study evaluates the effectiveness and safety of cyclosporine ( CsA ) in the treatment of patients with chronic idiopathic urticaria with a positive autologous serum skin test ( ASST ) , who fail to respond to conventional therapy , and requiring long-term oral steroid treatment . In a double-blind study , 40 adults were assigned r and omly to receive CsA ( 5 mg/kg per day for 8 weeks and then 4 mg/kg per day for 8 weeks ) or cetirizine ( 10 mg/day ) and then they were followed up for 9 months . After 2 weeks , the study was opened because 16 patients ( 40 % ) had daily severe relapses requiring systemic steroids treatment . All of these patients had been receiving antihistamines and , therefore , all patients also were assigned to the CsA treatment regimen ( 5 mg/kg per day for 8 weeks and then 4 mg/kg per day for 8 weeks ) . The ASST and clinical severity score were evaluated before and after treatment . All of the 40 patients completed the 16-week CsA course without dropping out because of relevant side effects . In three patients , CsA was reduced by 0.5 mg/kg per day after the 1st month of treatment for a mild and reversible increase in serum creatinine . During CsA treatment , 20 patients had relapses resolving spontaneously ( 8 patients ) or with antihistamines ( 12 patients ) . During the 9-month follow-up period , 22 patients had relapses resolving spontaneously ( 10 patients ) or with antihistamines ( 12 patients ) . Only two patients failed to complete the study because of severe symptoms occurring after 4 and 7 days of follow-up and requiring long-term steroid treatment . After 9 months of follow-up , 16 patients were still in full remission . The clinical severity score of chronic idiopathic urticaria dropped significantly by the end of the 4th month of treatment ( p = 0.002 ) as well as by the completion of follow-up ( p = 0.007 ) . The ASST was negative in 13 patients and positive in 3 of 16 patients , with total remission of symptoms . Significant score reduction also was observed in patients experiencing relapses that resolved spontaneously ( p = 0.005 ) or with antihistamines ( p = 0.03 ) . These results show the long-term efficacy and tolerability of CsA in patients with severe chronic idiopathic urticaria , unresponsive to conventional treatments The present study aim ed to evaluate the effectiveness of 2.5 mg/kg/day cyclosporin ( CsA ) treatment in patients with severe chronic idiopathic urticaria ( CIU ) and the impact of CsA treatment on several cytokines involved in the etiopathogenesis of CIU . Twenty-seven CIU patients and 24 healthy control subjects were included in the study . The autologous serum skin test ( ASST ) for autoantibodies and urticaria activity scoring ( UAS ) were measured for the evaluation of the clinical severity and the response to therapy , and the serum levels of interleukin (IL)-6 , IL-8 , IL-2 receptor , IL-1beta , tumor necrosis factor (TNF)-alpha and IL-5 were measured . The mean UAS score was 32.07 + /- 7.05 and 6.22 + /- 3.84 before and after CsA treatment , respectively . The serum IL-2 receptor , TNF-alpha and IL-5 levels of patients before CsA treatment were statistically higher than those of the control group ( P = 0.001 ) , and after 4 weeks of CsA therapy the mean IL-2R , TNF-alpha and IL-5 levels were significantly decreased . The data from this study demonstrate that CsA therapy is efficient and safe for CIU patients . Increase in clinical efficacy and marked decreases in serum cytokine levels suggest that inhibition of cytokine generation is involved in the action of the drug in this clinical setting BACKGROUND Chronic idiopathic urticaria is sometimes difficult to treat , with little response to antihistamine therapy . OBJECTIVE In a limited number of severe chronic idiopathic urticaria patients , cyclosporine A ( CsA ) therapy was found to be effective . In this study , we compared the clinical efficacy and safety of short- and long-term CsA applications . METHODS Twenty patients with severe disease , unresponsive to antihistamines and showing a positive autologous serum skin test ( ASST ) were r and omized to 4 mg/kg per day of CsA for 4 or 12 weeks . The clinical efficacy was measured with a daily activity score of weal numbers and itch ( UAS ) . The two groups were compared in terms of mean reduction in UAS and ASST response to pre- and post-treatment sera . RESULTS The clinical improvement was dramatic in the first month of treatment in both groups . There was no significant difference in the frequency of responses , side effects and the reduction of UAS in either group . CONCLUSION The preliminary results of our study suggest that CsA is clinical ly effective for chronic urticaria . The prolonged use of this therapy for more than 1 month provides little benefit in the clinical improvement Background : Because of specific method ological difficulties in conducting r and omized trials , surgical research remains dependent predominantly on observational or non‐r and omized studies . Few vali date d instruments are available to determine the method ological quality of such studies either from the reader 's perspective or for the purpose of meta‐ analysis . The aim of the present study was to develop and vali date such an instrument Chronic Idiopathic Urticaria ( CIU ) is a cutaneous disorder for which there is no identifiable specific etiologic agent . Some recent evidence s suggest that CIU might be an autoimmune disease . We analyzed immunological features occurring in CIU and evaluated effectiveness and tolerance of Cyclosporin A ( CsA ) treatment in patients unresponsive to antihistaminic treatment . Twenty patients with CIU were recruited after a selective diagnostic protocol and were divided into two groups . CsA was prescribed for group 1 and Prednisone for group 2 as control , for 8 weeks . Before and after the therapy we performed on all patients immunological studies . For all patients symptoms disappeared after a few days of therapy . Before therapy all patients showed activated B cells ( CD19+CD23 + cells ) and among B CD19 + cells , about 20 % were CD5 + ( cells that synthesize natural autoantibodies ) . After treatment with Prednisone in group 2 , a significant reduction of CD4 + lymphocytes ( p + 0,01 ) was observed . Our findings might support the CIU autoimmune pathogenetic hypothesis . The clinical remission in the CsA-treated group confirmed the therapeutic effectiveness of this therapy in antihistaminic unresponsive CIU and , at dosage used , side effects were rare , mild and reversible . Thus , CsA might be a good therapeutic alternative in CIU patients unresponsive to conventional treatments Patients with autoimmune urticaria ( AIU ) and positive autologous serum skin test ( ASST ) represent a more serious type of chronic urticaria that does not respond to treatment with antihistamines , but responds completely to systemic corticosteroids . Because of the chronic course of the disease , there is a risk of side-effects . Cyclosporin A ( CsA ) is an alternative treatment for patients with AIU . In order to determine the efficacy of CsA at the lowest possible dose in patients with chronic idiopathic urticaria and positive ASST , 30 patients were included in a 5-month study with a follow-up one year after the end of treatment . All patients had positive ASST before treatment and autoantibodies were present in 73 % . Twenty- three patients completed the study and responded to low-dose CsA treatment . Three patients did not respond to a dose of 2.5 mg/kg CsA , and 4 patients dropped-out due to side-effects . After the first month of treatment , an improvement of 31 % was noted , reaching 88 % after the fifth month of treatment . The mean dose of CsA was 2.16 mg/kg for the first month and 0.55 mg/kg for the fifth month . Three to 6 months after the end of the study , the ASST was repeated and was negative in 78.3 % of patients . At the one-year follow-up , 20 patients were symptom-free ( 87 % ) and 3 had relapsed ( 13 % ) . CsA , even in low-doses , can be an effective and short-term treat- ment with minimum side-effects in patients with AIU |
2,282 | 23,871,709 | This meta- analysis result suggested that EGFR or HER2 should have significant predictive ability for estimating overall survival in GC patients and may be useful for defining prognosis of GC patients | BACKGROUND AND AIMS Human epidermal growth factor receptor ( EGFR ) and HER2 ( ErbB2 ) both belong to EGFR family , which are overexpressed in a significant proportion of cases of gastric cancer ( GC ) .
Various studies have evaluated the prognostic value of EGFR or HER level in GC .
However , the overall test performance remains unclear .
We undertook this study to perform a systematic review and meta- analysis of prognostic cohort studies evaluating the use of EGFR or HER2 as a predictor of survival time in patients with GC . | Background The Trastuzumab for Gastric Cancer ( ToGA ) study is the first international trial to include Japanese patients with human epidermal growth factor 2 ( HER2 ) positive advanced/metastatic gastric or gastroesophageal junction cancer . ToGA showed that trastuzumab plus chemotherapy ( capecitabine/cisplatin or 5-fluorouracil/cisplatin ) improved overall survival in the overall population ( hazard ratio 0.74 ) . Regional differences in outcome in favor of Japanese population s were observed in other studies ; therefore , subgroup analyses of ToGA may contribute to the evaluation of the potential benefits of this regimen in Japanese patients . Methods We performed subgroup analyses on 101 Japanese patients enrolled into ToGA ( trastuzumab plus chemotherapy , n = 51 ; chemotherapy , n = 50 ) . Results Median overall survival in the Japanese subgroup was 15.9 months ( 95 % confidence interval 12–25 ) for trastuzumab plus chemotherapy and 17.7 months ( 95 % confidence interval 12–24 ) for chemotherapy ( hazard ratio 1.00 ; 95 % confidence interval 0.59–1.69 ) . After adjusting for prespecified covariates , the estimated hazard ratio for overall survival was 0.68 ( 95 % confidence interval 0.36–1.27 ) . Further post hoc and exploratory examinations supported the robustness of the adjusted hazard ratios . Conclusions After adjusting for imbalanced patient background s between arms , overall survival of Japanese patients with human epidermal growth factor 2 positive advanced/metastatic gastric or gastroesophageal junction cancer who received trastuzumab plus chemotherapy was improved compared with patients who received chemotherapy alone Objective : To better underst and the clinical implication s of insulin-like growth factor type 1 receptor ( IGF-1R ) , epidermal growth factor receptor ( EGFR ) and HER2 expressions in gastric cancer ( GC ) . Methods : The study group comprised 86 patients who received first-line chemotherapy for advanced GC at the National Cancer Center Hospital . Using laser-captured microdissection and a real-time RT-PCR assay , we quantitatively evaluated mRNA levels of IGF-1R , EGFR and HER2 in paraffin-embedded cancer specimens of surgically removed primary tumors . Results : In univariate analysis of the study group as a whole , patients with low expression of both IGF-1R and EGFR ( n = 13 ) had a significantly longer overall survival than the other patients ( n = 51 ; median , 24.6 vs. 12.8 months ; log-rank p = 0.013 ) . Multivariate survival analysis demonstrated that high EGFR expression [ hazard ratio , HR : 2.94 ( 95 % confidence interval , CI : 1.40–6.17 ) , p = 0.004 ] and poor performance status [ HR : 1.96 ( 95 % CI : 1.12–3.42 ) , p = 0.018 ] were significant predictors of poor survival . In patients given first-line S-1 monotherapy ( n = 29 ) , low IGF-1R ( p = 0.002 ) and low EGFR ( p = 0.035 ) gene expression correlated with a better response , without a significant prolongation of survival . Conclusion : Our data warrant further investigations on the strategy of co-targeting IGF-1R and EGFR in GC BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche Purpose : EGF receptor ( EGFR ) and HER2 positivity are considered to be negative prognostic factors in gastric cancer . Biomarker analysis was conducted to evaluate the impact of EGFR and HER2 expression on the outcome of patients enrolled in the Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer ( ACTS-GC ) , a r and omized controlled trial comparing postoperative adjuvant S-1 therapy with surgery alone in 1,059 patients with stage II/III gastric cancer . Experimental Design : Formalin-fixed , paraffin-embedded surgical specimens were retrospectively examined in 829 patients ( 78.3 % ) . The effects of EGFR and HER2 positivity on survival were analyzed on the basis of the 5-year survival data from the study . EGFR positivity was defined as an immunohistochemistry ( IHC ) score of 3 + , and HER2 positivity as an IHC score of 3 + or an IHC score of 2 + with a positive dual-color in situ hybridization status . Results : EGFR and HER2 were positive in 75 ( 9.0 % ) and 113 ( 13.6 % ) patients , respectively . The overall and relapse-free survival rates were significantly lower in EGFR-positive patients than in EGFR-negative patients , whereas they were similar in HER2-positive and HER2-negative patients . Multivariate analysis showed that EGFR positivity correlated with poor outcomes [ HR = 1.504 ; 95 % confidence interval ( CI ) = 1.020–2.149 ; P = 0.040 ] . Treatment with S-1 improved survival compared with surgery alone , irrespective of EGFR and HER2 status . Conclusions : EGFR positivity , but not HER2 positivity , was associated with poor patient outcomes after curative resection of stage II/III gastric cancer . There was no interaction between S-1 and EGFR or HER2 status with respect to survival outcome . Clin Cancer Res ; 18(21 ) ; 5992–6000 . © 2012 AACR The optimal adjuvant treatment for gastric cancer remains controversial . We compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen , in patients with high-risk gastric cancer , with that of the same chemotherapy plus radiation therapy ( RT ) . In addition , we evaluated the prognostic and /or predictive value of a panel of molecular markers . Patients with histologically proven , radically resected gastric cancer , stage ≥T3 and /or N+ were r and omized to 6 cycles of docetaxel with cisplatin , both at 75 mg/m2 every 3 weeks ( arm A ) or the same treatment with RT ( arm B ; 45 Gy ) . Due to excessive nausea and vomiting , cisplatin was substituted by carboplatin at AUC ( area under the curve ) of 5 after the first 45 patients ( 22 group A , 23 group B ) . The prognostic value of EGFR , ERCC1 , HER2 , MET/HGFR , MAP-Tau , and PTEN expression was also studied in a subset of 67 patients using immunohistochemistry on tissue microarrays ( TMAs ) . A total of 147 patients were r and omized . After a median follow-up of 53.7 months , no differences in overall ( OS ) and disease-free survival ( DFS ) were found between the two arms . The most common grade 3/4 toxicities for arms A and B ( excluding alopecia ) were non-febrile neutropenia ( 11 and 17 % , respectively ) , febrile neutropenia ( 9 and 7 % ) and diarrhea ( 7 and 4 % , respectively ) . Patients with ERCC1 positive tumors had significantly longer median DFS ( 33.1 vs. 11.8 months , Wald P = 0.016 ) and OS ( 63.2 vs. 18.8 months , Wald P = 0.046 ) . Our results indicate that the addition of RT to platinum/docetaxel adjuvant chemotherapy does not appear to improve survival in high-risk , radically resected gastric cancer . However , the possibility that a benefit by the addition of RT was not detected due to decreased power of the study should not be excluded BACKGROUND Cetuximab plus irinotecan/folinic acid/5-fluorouracil ( 5-FU ) ( IF ) was evaluated as first-line treatment of patients with advanced gastric cancer and gastroesophageal junction tumors . Preplanned analyses of the influence of tumor biomarkers on treatment outcome were carried out . PATIENTS AND METHODS Patients received weekly cetuximab ( 400 mg/m(2 ) on day 1 , subsequently 250 mg/m(2 ) ) plus irinotecan ( 80 mg/m(2 ) ) and a 24-hour continuous infusion of folinic acid ( 200 mg/m(2 ) ) and 5-FU ( 1500 mg/m(2 ) ) on days 1 , 8 , 15 , 22 , 29 and 36 of a 50-day cycle , until progressive disease ( PD ) . RESULTS The most common grade 3/4 toxic effects in 49 patients were diarrhea ( 15 % ) and skin toxic effects ( 14 % ) . In 48 assessable patients , the overall response rate was 46 % and disease control rate was 79 % . Median progression-free survival ( PFS ) and overall survival ( OS ) was 9.0 months [ 95 % confidence interval ( CI ) 7.1 - 15.6 ] and 16.5 months ( 95 % CI 11.7 - 30.1 ) , respectively . Tumor response was more common than nonresponse in epidermal growth factor receptor-expressing tumors ( P = 0.041 ) . Tumor PTEN expression was associated with longer PFS ( P = 0.035 ) and OS ( P = 0.0127 ) than no PTEN expression . CONCLUSION Cetuximab plus IF was well tolerated and efficacy data were encouraging . This treatment combination and the role of selected biomarkers are under investigation in the ongoing phase III EXP AND trial |
2,283 | 27,001,208 | Overall survival ( OS ) improved with the use of mTOR inhibitors and a SERD ; however , studies were not powered for an OS endpoint .
Study discontinuation rates and toxicity-related deaths were highest with VEGF inhibitors in combination with endocrine therapy , limiting their use in hormone receptor positive breast cancer .
CDK4/6 inhibitors and mTOR inhibitors appeared to have activity in both first and second line setting s , but required additional monitoring for common toxicities .
The activity of epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors was limited to the first-line setting and treatment discontinuation rates were higher than with mTOR inhibitors and SERDs .
Overall , PFS benefit appears to be greatest when agents acting on CDK4/6 , mTOR and Pi3 K pathways , and SERDs are added to st and ard endocrine therapy . | Endocrine therapy for the treatment of hormone receptor positive , HER2 negative , metastatic breast cancer is continually evolving .
We systematic ally review ed phase 2 and 3 r and omized controlled trials ( RCTs ) of agents used in this setting to assess the effectiveness and safety of these agents for postmenopausal women . | Purpose To compare overall survival ( OS ) for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for advanced breast cancer . Patients and Methods The Fulvestrant First-Line Study Comparing Endocrine Treatments ( FIRST ) was a phase II , r and omized , open-label , multicenter trial . Postmenopausal women with estrogen receptor – positive , locally advanced/metastatic breast cancer who had no previous therapy for advanced disease received either fulvestrant 500 mg ( days 0 , 14 , 28 , and every 28 days thereafter ) or anastrozole 1 mg ( daily ) . The primary end point ( clinical benefit rate [ 72.5 % and 67.0 % ] ) and a follow-up analysis ( median time to progression [ 23.4 months and 13.1 months ] ) have been reported previously for fulvestrant 500 mg and anastrozole , respectively . Subsequently , the protocol was amended to assess OS by unadjusted log-rank test after approximately 65 % of patients had died . Treatment effect on OS across several subgroups was examined . Tolerability was evaluated by adverse event monitoring . Results In total , 205 patients were r and omly assigned ( fulvestrant 500 mg , n = 102 ; anastrozole , n = 103 ) . At data cutoff , 61.8 % ( fulvestrant 500 mg , n = 63 ) and 71.8 % ( anastrozole , n = 74 ) had died . The hazard ratio ( 95 % CI ) for OS with fulvestrant 500 mg versus anastrozole was 0.70 ( 0.50 to 0.98 ; P = .04 ; median OS , 54.1 months v 48.4 months ) . Treatment effects seemed generally consistent across the subgroups analyzed . No new safety issues were observed . Conclusion There are several limitations of this OS analysis , including that it was not planned in the original protocol but instead was added after time-to-progression results were analyzed , and that not all patients participated in additional OS follow-up . However , the present results suggest fulvestrant 500 mg extends OS versus anastrozole . This finding now awaits prospect i ve confirmation in the larger phase III FALCON ( Fulvestrant and Anastrozole Compared in Hormonal Therapy Naïve Advanced Breast Cancer ) trial ( Clinical Trials.gov identifier : NCT01602380 ) PURPOSE To test whether combining bevacizumab , an anti-vascular endothelial growth factor treatment , with endocrine therapy ( ET ) could potentially delay the emergence of resistance to ET . PATIENTS AND METHODS A multicenter , r and omized , open-label , phase III , binational ( Spain and Germany ) study added bevacizumab ( 15 mg/kg every 3 weeks ) to ET ( ET-B ; letrozole or fulvestrant ) as first-line therapy in postmenopausal patients with human epidermal growth factor receptor 2 ( HER2 ) -negative and hormone receptor-positive advanced breast cancer . We compared progression-free survival ( PFS ) , overall survival ( OS ) , overall response rate ( ORR ) , response duration ( RD ) , time to treatment failure ( TTF ) , clinical benefit rate ( CBR ) , and safety . RESULTS From 380 patients recruited ( 2007 to 2011 ) , 374 were analyzed by intent to-treat ( 184 patients on ET and 190 patients on ET-B ) . Median age was 65 years , 270 patients ( 72 % ) had Eastern Cooperative Oncology Group performance status of 0 , 178 patients ( 48 % ) had visceral metastases , and 171 patients ( 46 % ) and 195 patients ( 52 % ) had received prior chemotherapy or ET , respectively . Median PFS was 14.4 months in the ET arm and 19.3 months in the ET-B arm ( hazard ratio , 0.83 ; 95 % CI , 0.65 to 1.06 ; P = .126 ) . ORR , CBR , and RD with ET versus ET-B were 22 % versus 41 % ( P < .001 ) , 67 % versus 77 % ( P = .041 ) , and 13.3 months versus 17.6 months ( P = .434 ) , respectively . TTF and OS were comparable in both arms . Grade 3 to 4 hypertension , aminotransferase elevation , and proteinuria were significantly higher in the ET-B arm . Eight patients ( 4.2 % ) receiving ET-B died during study or within 30 days of end of treatment . CONCLUSION The addition of bevacizumab to ET in first-line treatment failed to produce a statistically significant increase in PFS or OS in women with HER2-negative/hormone receptor-positive advanced breast cancer BACKGROUND The BOLERO-2 study previously demonstrated that adding everolimus ( EVE ) to exemestane ( EXE ) significantly improved progression-free survival ( PFS ) by more than twofold in patients with hormone-receptor-positive ( HR(+ ) ) , HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors ( NSAIs ) . The overall survival ( OS ) analysis is presented here . PATIENTS AND METHODS BOLERO-2 is a phase III , double-blind , r and omized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo ( PBO ) + EXE 25 mg/day in postmenopausal women with HR(+ ) advanced breast cancer with prior exposure to NSAIs . The primary end point was PFS by local investigator assessment ; OS was a key secondary end point . RESULTS At the time of data cutoff ( 3 October 2013 ) , 410 deaths had occurred and 13 patients remained on treatment . Median OS in patients receiving EVE + EXE was 31.0 months [ 95 % confidence interval ( CI ) 28.0 - 34.6 months ] compared with 26.6 months ( 95 % CI 22.6 - 33.1 months ) in patients receiving PBO + EXE ( hazard ratio = 0.89 ; 95 % CI 0.73 - 1.10 ; log-rank P = 0.14 ) . Post study treatments were received by 84 % of patients in the EVE + EXE arm versus 90 % of patients in the PBO + EXE arm . Types of post study therapies were balanced across arms , except for chemotherapy ( 53 % EVE + EXE versus 63 % PBO + EXE ) . No new safety concerns were identified . CONCLUSIONS In BOLERO-2 , adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinical ly meaningful and statistically significant improvement in the primary end point , PFS ( 4.6-months prolongation in median PFS ; P < 0.0001 ) . Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting . TRIAL REGISTRATION NUMBER NCT00863655 Fulvestrant fIRst-line Study comparing endocrine Treatments is a phase II , r and omized , open-label study comparing fulvestrant 500 mg with anastrozole 1 mg as first-line endocrine therapy for postmenopausal women with hormone receptor-positive ( HR+ ) advanced breast cancer . At data cut-off , only 36 % of patients had progressed and the median time to progression ( TTP ) had not been reached for fulvestrant . Here , we report follow-up data for TTP for fulvestrant 500 mg versus anastrozole 1 mg . Key inclusion criteria were postmenopausal women with estrogen receptor-positive and /or progesterone receptor-positive locally advanced or metastatic breast cancer and no prior endocrine therapy . Key exclusion criteria were presence of life-threatening metastases and prior treatment with a non-approved drug . Fulvestrant was administered 500 mg/month plus 500 mg on day 14 of month 1 ; anastrozole was administered 1 mg/day . TTP was defined by modified Response Evaluation Criteria in Solid Tumors v1.0 before data cut-off for the primary analysis , and investigator opinion after data cut-off . Best overall response to subsequent therapy and serious adverse events are also reported . In total , 205 patients received fulvestrant 500 mg ( n = 102 ) or anastrozole ( n = 103 ) . Follow-up analysis was performed when 79.5 % of patients had discontinued study treatment . Median TTP was 23.4 months for fulvestrant versus 13.1 months for anastrozole ; a 34 % reduction in risk of progression ( hazard ratio 0.66 ; 95 % confidence interval : 0.47 , 0.92 ; P = 0.01 ) . Best overall response to subsequent therapy and clinical benefit rate for subsequent endocrine therapy was similar between the treatment groups . No new safety concerns for fulvestrant 500 mg were documented . These longer-term , follow-up results confirm efficacy benefit for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for HR+ advanced breast cancer in terms of TTP , and , importantly , show similar best overall response rates to subsequent endocrine therapy Introduction Effective treatments for hormone-receptor-positive ( HR+ ) breast cancer ( BC ) following relapse/progression on nonsteroidal aromatase inhibitor ( NSAI ) therapy are needed . Initial Breast Cancer Trials of OraL EveROlimus-2 ( BOLERO-2 ) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival ( PFS ) versus placebo plus exemestane alone in this patient population . Methods BOLERO-2 is a phase 3 , double-blind , r and omized , international trial comparing everolimus ( 10 mg/day ) plus exemestane ( 25 mg/day ) versus placebo plus exemestane in postmenopausal women with HR+ advanced BC with recurrence/progression during or after NSAIs . The primary endpoint was PFS by local investigator review , and was confirmed by independent central radiology review . Overall survival , response rate , and clinical benefit rate were secondary endpoints . Results Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [ investigator review : 7.8 versus 3.2 months , respectively ; hazard ratio = 0.45 ( 95 % confidence interval 0.38–0.54 ) ; log-rank P < 0.0001 ; central review : 11.0 versus 4.1 months , respectively ; hazard ratio = 0.38 ( 95 % confidence interval 0.31–0.48 ) ; log-rank P < 0.0001 ] in the overall population and in all prospect ively defined subgroups , including patients with visceral metastases , patients with recurrence during or within 12 months of completion of adjuvant therapy , and irrespective of age . The incidence and severity of adverse events were consistent with those reported at the interim analysis and in other everolimus trials . Conclusion The addition of everolimus to exemestane markedly prolonged PFS in patients with HR+ advanced BC with disease recurrence/progression following prior NSAIs . These results further support the use of everolimus plus exemestane in this patient population . Clinical Trials.gov # NCT00863655 Background At the time of the initial analysis of overall survival ( OS ) for the Comparison of Faslodex in Recurrent or Metastatic Breast Cancer ( CONFIRM ) r and omized , double-blind , phase III trial , approximately 50 % of patients had died . A final analysis of OS was subsequently planned for when 75 % of patients had died . Methods Patients were r and omly assigned 1:1 to fulvestrant 500 mg administered as two 5-mL intramuscular injections on days 0 , 14 , and 28 and every 28 ( ±3 ) days thereafter or fulvestrant 250 mg administered as two 5-mL intramuscular injections ( one fulvestrant and one placebo [ identical in appearance to study drug ] ) on days 0 , 14 ( two placebo injections only ) , and 28 and every 28 ( ±3 ) days thereafter . OS was analyzed using an unadjusted log-rank test . No adjustments were made for multiplicity . Serious adverse events ( SAEs ) and best response to subsequent therapy were also reported . All statistical tests were two-sided . Results In total , 736 women ( median age = 61.0 years ) were r and omly assigned to fulvestrant 500 mg ( n = 362 ) or 250 mg ( n = 374 ) . At the final survival analysis , 554 of 736 ( 75.3 % ) patients had died . Median OS was 26.4 months for fulvestrant 500 mg and 22.3 months for 250 mg ( hazard ratio = 0.81 ; 95 % confidence interval = 0.69–0.96 ; nominal P = .02 ) . There were no clinical ly important differences in SAE profiles between the treatment groups ; no clustering of SAEs could be detected in either treatment group . Type of first subsequent therapy and objective responses to first subsequent therapy were well balanced between the two treatment groups . Conclusions In patients with locally advanced or metastatic estrogen receptor – positive breast cancer , fulvestrant 500 mg is associated with a 19 % reduction in risk of death and a 4.1-month difference in median OS compared with fulvestrant 250 mg . Fulvestrant 500 mg was well tolerated , and no new safety concerns were identified PURPOSE CALGB 40302 sought to determine whether lapatinib would improve progression-free survival ( PFS ) among women with hormone receptor-positive metastatic breast cancer treated with fulvestrant . PATIENTS AND METHODS Eligible women had estrogen receptor-positive and /or progesterone receptor-positive tumors , regardless of human epidermal growth factor receptor 2 ( HER2 ) status , and prior aromatase inhibitor treatment . Patients received fulvestrant 500 mg intramuscularly on day 1 , followed by 250 mg on days 15 and 28 and every 4 weeks thereafter , and either lapatinib 1,500 mg or placebo daily . The study planned to accrue 324 patients and was powered for a 50 % improvement in PFS with lapatinib from 5 to 7.5 months . RESULTS At the third planned interim analysis , the futility boundary was crossed , and the data and safety monitoring board recommend study closure , having accrued 295 patients . At the final analysis , there was no difference in PFS ( hazard ratio [ HR ] of placebo to lapatinib , 1.04 ; 95 % CI , 0.82 to 1.33 ; P = .37 ) ; median PFS was 4.7 months for fulvestrant plus lapatinib versus 3.8 months for fulvestrant plus placebo . There was no difference in overall survival ( OS ) ( HR , 0.91 ; 95 % CI , 0.68 to 1.21 ; P = .25 ) . For HER2-normal tumors , median PFS did not differ by treatment arm ( 4.1 v 3.8 months ) . For HER2-positive tumors , lapatinib was associated with longer median PFS ( 5.9 v 3.3 months ) , but the differential treatment effect by HER2 status was not significant ( P = .53 ) . The most frequent toxicities were diarrhea , fatigue , and rash associated with lapatinib . CONCLUSION Adding lapatinib to fulvestrant does not improve PFS or OS in advanced ER-positive breast cancer and is more toxic PURPOSE To compare the effect of therapy with anastrozole versus a combination of fulvestrant and anastrozole in women in first relapse of endocrine-responsive breast cancer . PATIENTS AND METHODS Postmenopausal women , or premenopausal women receiving a gonadotropin-releasing hormone agonist , with estrogen receptor- and /or progesterone receptor-positive disease at first relapse after primary treatment of localized disease were open-label r and omly assigned to a fulvestrant loading dose ( LD ) regimen followed by monthly injection plus 1 mg of anastrozole daily or to 1 mg of anastrozole daily alone . The primary end point was time to progression ( TTP ) . RESULTS In all , 514 women were r and omly assigned to fulvestrant plus anastrozole ( experimental arm ; n = 258 ) or anastrozole ( st and ard arm ; n = 256 ) . Approximately two thirds had received adjuvant antiestrogens , but only eight individuals had received an aromatase inhibitor . Median TTP was 10.8 and 10.2 months in the experimental versus st and ard arm , respectively ( hazard ratio [ HR ] = 0.99 ; 95 % CI , 0.81 to 1.20 ; P = .91 ) ; median overall survival was 37.8 and 38.2 months , respectively ( HR = 1.0 ; 95 % CI , 0.76 to 1.32 ; P = 1.00 ) . Incidences of prespecified adverse events ( AEs ) were similar . Hot flashes were more common in the experimental arm : 63 patients ( 24.6 % ) versus 35 patients ( 13.8 % ) in the st and ard arm ( P = .0023 ) . Death owing to AEs was reported in 11 ( 4.3 % ) and five patients ( 2.0 % ) in the experimental versus st and ard arm , respectively . CONCLUSION Fulvestrant ( 250 mg + LD regimen ) in combination with anastrozole offered no clinical efficacy advantage over anastrozole monotherapy in this population of individuals with a relatively high proportion of previous adjuvant antiestrogen exposure BACKGROUND Insulin-like growth factors ( IGF-1 and IGF-2 ) bind to the IGF-1 receptor ( IGF-1R ) , increasing cell proliferation and survival . Ganitumab is a monoclonal IgG1 antibody that blocks IGF-1R . We tested the efficacy and safety of adding ganitumab to endocrine treatment for patients with hormone-receptor-positive breast cancer . METHODS We did this phase 2 trial in outpatient clinics and hospitals . We enrolled postmenopausal women with hormone-receptor-positive , locally advanced or metastatic breast cancer previously treated with endocrine treatment . They were r and omly assigned ( 2:1 ) with a central r and omisation schedule to receive intravenous ganitumab 12 mg per kg bodyweight or placebo in combination with open-label intramuscular fulvestrant ( 500 mg on day 1 , then 250 mg on days 15 , 29 , and every 28 days ) or oral exemestane ( 25 mg once daily ) on a 28-day cycle . Patients , investigators , study monitors , and the sponsor staff were masked to treatment allocation . Response was assessed every 8 weeks . The primary endpoint was median progression-free survival in the intention-to-treat population . We analysed overall survival as one of our secondary endpoints . The study is registered at Clinical Trials.gov , number NCT00626106 . FINDINGS We screened 189 patients and enrolled 156 ( 106 in the ganitumab group and 50 in the placebo group ) . Median progression-free survival did not differ significantly between the ganitumab and placebo groups ( 3·9 months , 80 % CI 3·6 - 5·3 vs 5·7 months , 4·4 - 7·4 ; hazard ratio [ HR ] 1·17 , 80 % CI 0·91 - 1·50 ; p=0·44 ) . However , overall survival was worse in the the ganitumab group than in the placebo group ( HR 1·78 , 80 % CI 1·27 - 2·50 ; p=0·025 ) . With the exception of hyperglycaemia , adverse events were generally similar between groups . The most common grade 3 or higher adverse event was neutropenia-reported by six of 106 ( 6 % ) patients in the ganitumab group and one of 49 ( 2 % ) in the placebo group . Hyperglycaemia was reported by 12 of 106 ( 11 % ) patients in the ganitumab group ( with six patients having grade 3 or 4 hyperglycaemia ) and none of 49 in the placebo group . Serious adverse events were reported by 27 of 106 ( 25 % ) patients in the ganitumab group and nine of 49 ( 18 % ) patients in the placebo group . INTERPRETATION Addition of ganitumab to endocrine treatment in women with previously treated hormone-receptor-positive locally advanced or metastatic breast cancer did not improve outcomes . Our results do not support further study of ganitumab in this subgroup of patients . FUNDING Amgen This paper is an overview of the new response evaluation criteria in solid tumours : revised RECIST guideline ( version 1 . 1 ) , with a focus on up date d contents BACKGROUND Palbociclib ( PD-0332991 ) is an oral , small-molecule inhibitor of cyclin-dependent kinases ( CDKs ) 4 and 6 with pre clinical evidence of growth-inhibitory activity in oestrogen receptor-positive breast cancer cells and synergy with anti-oestrogens . We aim ed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced , oestrogen receptor-positive , HER2-negative breast cancer . METHODS In this open-label , r and omised phase 2 study , postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease were eligible to participate . Patients were enrolled in two separate cohorts that accrued sequentially : in cohort 1 , patients were enrolled on the basis of their oestrogen receptor-positive and HER2-negative biomarker status alone , whereas in cohort 2 they were also required to have cancers with amplification of cyclin D1 ( CCND1 ) , loss of p16 ( INK4A or CDKN2A ) , or both . In both cohorts , patients were r and omly assigned 1:1 via an interactive web-based r and omisation system , stratified by disease site and disease-free interval , to receive continuous oral letrozole 2.5 mg daily or continuous oral letrozole 2.5 mg daily plus oral palbociclib 125 mg , given once daily for 3 weeks followed by 1 week off over 28-day cycles . The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population . Accrual to cohort 2 was stopped after an unplanned interim analysis of cohort 1 and the statistical analysis plan for the primary endpoint was amended to a combined analysis of cohorts 1 and 2 ( instead of cohort 2 alone ) . The study is ongoing but closed to accrual ; these are the results of the final analysis of progression-free survival . The study is registered with the Clinical Trials.gov , number NCT00721409 . FINDINGS Between Dec 22 , 2009 , and May 12 , 2012 , we r and omly assigned 165 patients , 84 to palbociclib plus letrozole and 81 to letrozole alone . At the time of the final analysis for progression-free survival ( median follow-up 29.6 months [ 95 % CI 27.9 - 36.0 ] for the palbociclib plus letrozole group and 27.9 months [ 25.5 - 31.1 ] for the letrozole group ) , 41 progression-free survival events had occurred in the palbociclib plus letrozole group and 59 in the letrozole group . Median progression-free survival was 10.2 months ( 95 % CI 5.7 - 12.6 ) for the letrozole group and 20.2 months ( 13.8 - 27.5 ) for the palbociclib plus letrozole group ( HR 0.488 , 95 % CI 0.319 - 0.748 ; one-sided p=0.0004 ) . In cohort 1 ( n=66 ) , median progression-free survival was 5.7 months ( 2.6 - 10.5 ) for the letrozole group and 26.1 months ( 11.2-not estimable ) for the palbociclib plus letrozole group ( HR 0.299 , 0.156 - 0.572 ; one-sided p<0.0001 ) ; in cohort 2 ( n=99 ) , median progression-free survival was 11.1 months ( 7.1 - 16.4 ) for the letrozole group and 18.1 months ( 13.1 - 27.5 ) for the palbociclib plus letrozole group ( HR 0.508 , 0.303 - 0.853 ; one-sided p=0.0046 ) . Grade 3 - 4 neutropenia was reported in 45 ( 54 % ) of 83 patients in the palbociclib plus letrozole group versus one ( 1 % ) of 77 patients in the letrozole group , leucopenia in 16 ( 19 % ) versus none , and fatigue in four ( 4 % ) versus one ( 1 % ) . Serious adverse events that occurred in more than one patient in the palbociclib plus letrozole group were pulmonary embolism ( three [ 4 % ] patients ) , back pain ( two [ 2 % ] ) , and diarrhoea ( two [ 2 % ] ) . No cases of febrile neutropenia or neutropenia-related infections were reported during the study . 11 ( 13 % ) patients in the palbociclib plus letrozole group and two ( 2 % ) in the letrozole group discontinued the study because of adverse events . INTERPRETATION The addition of palbociclib to letrozole in this phase 2 study significantly improved progression-free survival in women with advanced oestrogen receptor-positive and HER2-negative breast cancer . A phase 3 trial is currently underway . FUNDING Pfizer PURPOSE We compared fulvestrant 500 mg regimen with the approved dose of fulvestrant 250 mg per month for treatment of postmenopausal women with estrogen receptor-positive advanced breast cancer who experienced progression after prior endocrine therapy . PATIENTS AND METHODS Comparison of Faslodex in Recurrent or Metastatic Breast Cancer ( CONFIRM ) is a double-blind , parallel-group , multicenter , phase III study . Patients were r and omly assigned to fulvestrant 500 mg ( 500 mg intramuscularly [ IM ] on day 0 , then 500 mg IM on days 14 and 28 and every 28 days thereafter ) or 250 mg every 28 days . Primary end point was progression-free survival ( PFS ) . Secondary end points included objective response rate , clinical benefit rate ( CBR ) , duration of clinical benefit ( DoCB ) , overall survival ( OS ) , and quality of life ( QOL ) . RESULTS PFS was significantly longer for fulvestrant 500 mg ( n = 362 ) than 250 mg ( n = 374 ) ( hazard ratio [ HR ] = 0.80 ; 95 % CI , 0.68 to 0.94 ; P = .006 ) , corresponding to a 20 % reduction in risk of progression . Objective response rate was similar for fulvestrant 500 mg and 250 mg ( 9.1 % v 10.2 % , respectively ) . CBR was 45.6 % for fulvestrant 500 mg and 39.6 % for fulvestrant 250 mg . DoCB and OS were 16.6 and 25.1 months , respectively , for the 500-mg group , whereas DoCB and OS were 13.9 and 22.8 months , respectively , in the 250-mg group . Fulvestrant 500 mg was well tolerated with no dose-dependent adverse events . QOL was similar for both arms . CONCLUSION Fulvestrant 500 mg was associated with a statistically significant increase in PFS and not associated with increased toxicity , corresponding to a clinical ly meaningful improvement in benefit versus risk compared with fulvestrant 250 mg |
2,284 | 26,110,546 | Most of the orthopaedic physical therapists in the United States who responded to our survey reported that they used lumbar traction , though not necessarily consistent with proposed criteria that identify patients most likely to benefit from traction .
They used various traction delivery modes/parameters and used traction within comprehensive plans of care incorporating multiple interventions .
Professional characteristics ( education levels and clinical specialist credentialing ) were associated with traction usage | OBJECTIVES To examine how many physical therapists use traction , the patients for whom traction is used , the preferred delivery modes/parameters of traction , the supplemental interventions used with traction , and whether professional characteristics influence traction usage .
BACKGROUND Several systematic review s and clinical guidelines have question ed the effectiveness of traction for managing low back pain , yet some patients may benefit from lumbar traction .
While traction usage among physical therapists in other countries has been described , usage among physical therapists in the United States has not been examined . | The objective of the study was to establish the specific use of advice and exercise by physiotherapists , for the management of chronic low back pain ( LBP ) . A question naire was mailed to a r and om sample of 600 members of the Irish Society of Chartered Physiotherapists . Open and closed questions were used to obtain information on treatments provided to chronic LBP patients . Respondents ' treatment goals were also investigated , along with the typical methods used to assess treatment outcome . Four hundred and nineteen of the sample returned the question naire ; 280/419 ( 67 % ) indicated that they currently treated LBP of which 76 % ( n=214 ) were senior grade therapists . Advice and exercise , respectively , were the treatments most frequently used for chronic LBP : advice was most commonly delivered as part of an exercise programme , with strengthening ( including core stability ) the most frequently used exercise type . Supervision of exercise and follow-up advice were underutilised with respect to the recommendations of relevant clinical guidelines . Pain relief was an important treatment goal . Emphasis on exercise programme supervision , incorporating reassurance that its safe to stay active and ' hurt does not mean harm ' , must be more effectively disseminated and promoted in practice . The influence of follow-up advice on exercise adherence warrants further investigation Background Traction is commonly used for the treatment of low back pain ( LBP ) , predominately with nerve root involvement ; however its benefits remain to be established . The aim of this study was to test the feasibility of a pragmatic r and omized controlled trial to compare the difference between two treatment protocol s ( manual therapy , exercise and advice , with or without traction ) in the management of acute/sub acute LBP with ' nerve root ' involvement . Methods 30 LBP patients with nerve root pain were recruited and r and omly assigned to one of two treatment groups . Primary outcome measures were the : McGill pain question naire , Rol and Morris disability question naire , and the SF36 Question naire ; recorded at baseline , discharge , 3 and 6 months post-discharge . Results 27 patients completed treatment with a loss of another four patients at follow up . Intention to treat analysis demonstrated an improvement in all outcomes at follow up points but there appeared to be little difference between the groups . Conclusion This study has shown that a trial recruiting patients with ' nerve root ' problems is feasible . Further research based upon a fully powered trial is required to ascertain if the addition of traction has any benefit in the management of these patients .Trial Registration Registration number : IS RCT BACKGROUND AND PURPOSE Since the release of acute low back pain management guidelines in 1994 , little was known about the effect of these guidelines on clinical practice . The purpose of this study was to examine physical therapists ' reported management of acute and subacute lumbar impairment . SUBJECTS One in 10 registered physical therapists who were r and omly selected from southern Ontario , Canada , ( n=454 ) and all registered physical therapists from northern Ontario ( n=331 ) were surveyed . METHODS In the question naire , case scenarios covered 3 areas related to the management of lumbar impairment : ( 1 ) physical examination , ( 2 ) treatment and recommendations , and ( 3 ) therapists ' beliefs regarding its management . RESULTS Five hundred sixty-nine question naires were returned ( response rate=72.5 % ) . Only data obtained for therapists ( n=274 ) whose weekly workload included more than 10 % of people with lumbar impairment were used in the analysis . Overall , patient education , exercise , and electrotherapeutic and thermal modalities were the preferred interventions for acute lumbar impairment ( symptom onset of less than 5 weeks ) with or without sciatica , whereas exercise and work modification were preferred for subacute lumbar impairment ( symptom onset of 5 weeks or longer ) . There was a trend of using electrotherapeutic and thermal modalities with uncertain effectiveness . Only 46.3 % of the therapists agreed or strongly agreed that practice guidelines were useful for managing lumbar impairment . DISCUSSION AND CONCLUSION Although the physical therapists surveyed , in general , followed the guidelines in managing acute lumbar impairment , they felt uncertain regarding the value of practice guidelines . Future research should focus on identifying effective treatment approaches and exploring the effectiveness of practice guidelines Background Patients with signs of nerve root irritation represent a sub-group of those with low back pain who are at increased risk of persistent symptoms and progression to costly and invasive management strategies including surgery . A period of non-surgical management is recommended for most patients , but there is little evidence to guide non-surgical decision-making . We conducted a preliminary study examining the effectiveness of a treatment protocol of mechanical traction with extension-oriented activities for patients with low back pain and signs of nerve root irritation . The results suggested this approach may be effective , particularly in a more specific sub-group of patients . The aim of this study will be to examine the effectiveness of treatment that includes traction for patients with low back pain and signs of nerve root irritation , and within the pre-defined sub-group . Methods / Design The study will recruit 120 patients with low back pain and signs of nerve root irritation . Patients will be r and omized to receive an extension-oriented treatment approach , with or without the addition of mechanical traction . R and omization will be stratified based on the presence of the pre-defined sub-grouping criteria . All patients will receive 12 physical therapy treatment sessions over 6 weeks . Follow-up assessment s will occur after 6 weeks , 6 months , and 1 year . The primary outcome will be disability measured with a modified Oswestry question naire . Secondary outcomes will include self-reports of low back and leg pain intensity , quality of life , global rating of improvement , additional healthcare utilization , and work absence . Statistical analysis will be based on intention to treat principles and will use linear mixed model analysis to compare treatment groups , and examine the interaction between treatment and sub-grouping status . Discussion This trial will provide a method ologically rigorous evaluation of the effectiveness of using traction for patients with low back pain and signs of nerve root irritation , and will examine the validity of a pre-defined sub-grouping hypothesis . The results will provide evidence to inform non-surgical decision-making for these patients .Trial Registration This trial has been registered with http:// Clinical Trials.gov : Four treatment regimens for patients with specified combinations of low back pain and sciatica were evaluated . The largest group studied had low back pain with limited straight-leg raising ( SLR ) and in them the beneficial effect of manipulation in hastening pain relief was highly significant . In similar patients without limitation of SLR , the effect was of borderline significance . In all the other groups , treated patients also recovered more quickly than their controls . Traction , for patients with low back pain and sciatica , and epidural injections when a root palsy was present also produced some significant pain relief . The effect of sclerosants for back pain was less clear BACKGROUND CONTEXT Low back pain ( LBP ) is a prevalent disorder in society that has been associated with increased loss of work time and medical expenses . A common intervention for LBP is spinal manipulation , a technique that is not specific to one scope of practice or profession . PURPOSE The purpose of this systematic review was to examine the effectiveness of physical therapy spinal manipulations for the treatment of patients with low back pain . METHODS A search of the current literature was conducted using PubMed , CINAHL , SPORTD iscus , Pro Quest Nursing and Allied Health Source , Scopus , and Cochrane Controlled Trials Register . Studies were included if each involved : 1 ) individuals with LBP ; 2 ) spinal manipulations performed by physical therapists compared to any control group that did not receive manipulations ; 3 ) measurable clinical outcomes or efficiency of treatment measures , and 4 ) r and omized control trials . The quality of included articles was determined by two independent authors using the criteria developed and used by the Physiotherapy Evidence Data base ( PEDro ) . RESULTS Six r and omized control trials met the inclusion criteria of this systematic review . The most commonly used outcomes in these studies were some variation of pain rating scales and disability indexes . Notable results included varying degrees of effect sizes favoring physical therapy spinal manipulations and minimal adverse events result ing from this intervention . Additionally , the manipulation group in one study reported statistically significantly less medication use , health care utilization , and lost work time . CONCLUSION Based on the findings of this systematic review there is evidence to support the use of spinal manipulation by physical therapists in clinical practice . Physical therapy spinal manipulation appears to be a safe intervention that improves clinical outcomes for patients with low back pain PURPOSE S to compare the efficacy of mechanical lumbar traction with low ( 10 % of body weight ) and high traction force ( 50 % of body weight ) on the separation of the vertebrae in vivo using stature variations as criterion . Additionally , we aim ed to determine the time that the effects of traction last . MATERIAL AND METHODS Thirty apparently healthy subjects ( age : 20.9 ± 1.7 years old ) , 14 male and 16 female , were su bmi tted to two protocol s of 15 minutes of continuous traction ( with intensity of 10 % and 50 % of body weight ) , in two sessions one week apart . The protocol order was determined r and omly . Stature was assessed before and immediately after the traction and every five minutes for 30 minutes after traction ceased . RESULTS Immediately after the traction both protocol s induced a significant increase in stature , however the magnitude of the increase was significantly superior in the traction with 50 % of body weight ( 0.567 ± 0.049 vs. 0.298 ± 0.041 cm , p>0.001 ) . After the traction with 50 % of body weight the increase in the stature was maintained until ten minutes after the end of the traction , while after the traction with 10 % of body weight the effects on stature disappeared after five minutes . CONCLUSIONS The mechanical vertebral traction of the lumbar region performed continuously with 50 % of body weight during 15 minutes induced an increase in stature superior and longer in time than that observed with a traction force of 10 % of body weight STUDY DESIGN Single group test-retest repeated measures . OBJECTIVES To determine the effects of lumbar traction with 3 different amounts of force ( 10 % , 30 % and 60 % body weight ) on pain-free mobility of the lower extremity as measured by the straight leg raise ( SLR ) test . BACKGROUND There are several recommendations on how lumbar traction should be performed , but the duration , frequency , force , and type of technique to be applied differ among the sources . METHODS AND MEASURES Ten subjects with subjective complaints of low back pain or radicular symptoms with a positive unilateral SLR test below 45 degrees participated in this study . The pain-free mobility of the lower extremity in the SLR test position was measured prior to and immediately following 5 minutes of static traction in the supine position . R and om assignment in the order of the amount of applied traction was implemented . RESULTS The straight leg raise measurements were found to be significantly greater immediately following 30 % and 60 % of body weight traction as compared to pretraction and 10 % of body weight traction . The mean ( SD ) SLR measurements were pretraction ( 24.1 degrees + /- 13.0 ) , 10 % of body weight traction ( 27.4 degrees + /- 14.5 ) , 30 % of body weight traction ( 34.0 degrees + /- 14.3 ) , 60 % of body weight traction ( 36.5 degrees + /- 15.8 ) . CONCLUSIONS The results of this study indicate that traction in this group of patients improved the mobility of the lower extremity during the SLR test . Both 30 % and 60 % of body weight tractions were shown to be effective for increasing motion beyond pretraction levels Study Design . A prospect i ve , consecutive , cohort study of patients with acute low back pain classified into subgroups based on examination data and treated with a specific treatment approach . Objective . To calculate the interrater reliability of a classification system , and to compare initial patient characteristics and outcomes of physical therapy treatment when a classification approach is used . Summary of Background Data . Classification of patients with low back pain into homogeneous subgroups has been identified as a research priority . Identifying relevant subgroups of patients could improve clinical outcomes and research efficiency . Methods . Consecutive patients referred to physical therapy for treatment of acute low back pain were evaluated and classified into one of four subgroups ( immobilization , mobilization , specific exercise , or traction ) before treatment . Physical therapy treatment was based on the patient ’s classification . The classifications were compared for initial patient characteristics , frequency and duration of physical therapy , and improvement in Oswestry scores . Results . In this study , 120 patients were evaluated and classified . Analysis of interrater reliability showed a kappa value of 0.56 . Differences were found among the classifications for age , initial Oswestry score , history of low back pain , symptom distribution , and average change in Oswestry score with treatment . Conclusions . Reaching a consensus regarding relevant patient subgroups requires data on the reliability and validity of existing classification systems . Further work is required to vali date improvement in treatment outcomes using a classification approach Study Design . A r and omized clinical trial . Objectives . To assess the efficacy of motorized continuous traction for low back pain . Summary of Background Data . The available studies on the efficacy of lumbar traction do not allow clear conclusions because of severe method ologic flaws . The current trial aim ed to overcome these shortcomings . Methods . Patients with at least 6 weeks of nonspecific low back pain were selected . High‐dose traction was compared with sham ( or low‐dose ) traction . Sham traction was given with a specially developed brace that becomes tighter in the back during traction . This was experienced as if real traction were exerted . The patients and the outcome assessor were unaware of treatment allocation . Outcome measures were : patient 's global perceived effect , severity of main complaints , functional status , pain , range of motion , work absence , and medical treatment . Results for the outcome measures at 12 weeks and 6 months after r and omization are presented . Results . One hundred and fifty‐one patients were r and omly allocated to one of the two treatment methods . Intention‐to‐treat analysis of the 12‐week and 6‐month results showed no statistically significant differences between the groups on all outcome measures ; all 95 % confidence intervals included the value zero . The number of patients lost to follow‐up study was very low . Other analyses showed the same results . Conclusions . Most common flaws of earlier studies on traction therapy could be overcome . This trial did not support the cl aim that traction is efficacious for patients with low back pain OBJECTIVE To examine the association between question naire length and response rate in a mailed survey of generalist physicians r and omly selected from the American Medical Association master file . STUDY DESIGN AND SETTING In a pilot study , otherwise similar question naires of 30 different lengths ( 849 to 1,867 words ) were mailed to 192 physicians in April 1999 . In the main study , question naires of 16 different lengths ( 564 to 988 words ) were mailed to 1,700 physicians between June 1999 and January 2000 . RESULTS In the pilot study , response rate decreased from 60 % for question naires 849 words in length to 16.7 % for question naires over 1,800 words in length . Logistic regression revealed an odds ratio of 0.887 ( 95%CI 0.813 , 0.968 ; p=0.006 ) for word count , expressed in units of 100 words . In the main study , response rate varied between 51.5 % and 71.4 % . Logistic regression showed no association between response and word count ( OR 0.988 ; 95%CI 0.896 , 1.090 ; p=0.81 ) . CONCLUSION There appears to have been a threshold in these studies of approximately 1,000 words . Question naires above the threshold had lower response rates than those below it ( 38.0 % vs. 59.4 % ) OBJECTIVE To identify the current use of traction and the types of patients , treatment parameters , and treatment modalities used in conjunction with traction . DESIGN Postal survey , with 4 sections : professional characteristics of respondent , current use of traction , patient selection , and treatment parameters . SETTING Musculoskeletal outpatient departments ( private and nonprivate practitioners ) . PARTICIPANTS R and om sample ( N=1491 ) of chartered physiotherapists in the UK who work in the management of low back pain ( LBP ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Descriptive analysis of information on current use and practice in applying traction . RESULTS A response rate of 83 % ( n=1239 ) was achieved ; 41 % ( n=507 ) use lumbar traction , which is most commonly used in the management of subacute LBP patients presenting with nerve root symptoms . Treatment parameters were established for weights ( 5 - 60 kg ) , frequency ( 2 - 3 times weekly ) , and length of treatment ( 4 wk ) . In addition , traction is commonly used with other modalities ( 87 % ) : mobilizations , advice , and exercise . CONCLUSIONS Survey results show the continued use of lumbar traction despite the recommendations of numerous guidelines . Results also clarify the types of patients and the parameters used in the application of traction This study investigates whether there is a difference in electromyographic activity in the lumbar sacrospinalis musculature during continuous and intermittent pelvic traction . Twenty-nine normal subjects were r and omly assigned to a control group , a continuous traction group , or an intermittent traction group . Electromyographic activity was recorded at specific timed intervals . Myoelectric activity increased with the onset of either type of traction , but by the third recording both groups had returned to their normal initial resting myoelectric recordings . The myoelectric patterns over time were similar for the two treatment groups . No significant difference in electromyographic activity of the lumbar sacrospinalis musculature during intermittent or continuous pelvic traction was found . J Orthop Sports Phys Ther 1981;2(3):137 - 141 STUDY DESIGN Effect of clinical specialization was studied in a retrospective analysis of a commercial outcomes data base . OBJECTIVE To assess effectiveness of care as measured by changes in health status and efficiency as measured by visits , duration of treatment episode , and net revenue between patients treated by clinicians with and without orthopaedic clinical specialist certification ( OCS ) . BACKGROUND Clinical specialization is becoming common in physical therapy , but there are no studies to support improved efficiency or effectiveness with advanced practitioner competencies . METHODS AND MEASURES A total of 258 adults treated in practice s participating in the Focus on Therapeutic Outcomes process during 1996 comprised the data set . Seven physical therapists with OCS treated 129 patients ( clinical specialist group ) . These patients were matched to 129 patients not treated by physical therapists with OCS ( comparison group ) r and omly chosen from the aggregate data set . All patients completed a st and ardized health status question naire at initial evaluation and discharge . St and ardized response means ( SRMs ) were calculated to measure change during treatment . RESULTS Therapists with OCS were more efficient than therapists without OCS , using fewer visits ( 9.1 + /- 6.7 vs 11.2 + /- 7.4 ) for less estimated cost ( $ 949 + /- $ 736 vs $ 1238 + /- $ 1227 ) during the same treatment duration ( 35.9 + /- 48.3 vs 35.4 + /- 25.6 days ) and performed fewer treatment procedures . Overall , there was no difference in effectiveness as measured by change in health status , that is , unit of functional improvement per episode ( 0.89 + /- 1.0 SRM for clinical specialists compared with 0.88 + /- 1.0 SRM for comparison group ) . The OCS group had better value ( unit of functional improvement per estimated dollar ) and utilization ( unit of functional improvement per visit ) for the constructs of physical functioning ( value : 1.31 + /- 2.7 vs 0.78 + /- 1.8 ; utilization : 1.25 + /- 2.2 vs 0.76 + /- 1.6 ) and role physical ( value : 1.26 + /- 2.9 vs 0.44 + /- 3.5 ; utilization : 1.11 + /- 1.9 vs 0.51 + /- 2.3 ) ( SRMs for OCS group vs comparison group , respectively ) . CONCLUSIONS Our data support the conclusion that physical therapists with OCS are more efficient compared with clinicians without OCS . Study limitations in design , small sample size , and low number of clinicians are discussed |
2,285 | 31,830,138 | Some specialties might be at higher risk such as anesthesiologists , psychiatrists , general practitioners and general surgeons .
Physicians are an at-risk profession of suicide , with women particularly at risk .
The rate of suicide in physicians decreased over time , especially in Europe . | BACKGROUND Medical-related professions are at high suicide risk .
However , data are contradictory and comparisons were not made between gender , occupation and specialties , epochs of times .
Thus , we conducted a systematic review and meta- analysis on suicide risk among health-care workers . | Abstract Purpose To compare tachycardia and cardiac strain between 24-hour shifts ( 24hS ) and 14-hour night shifts ( 14hS ) in emergency physicians ( EPs ) , and to investigate key factors influencing tachycardia and cardiac strain . Methods We monitored heart rate ( HR ) with Holter-ECG in a shift-r and omized trial comparing a 24hS , a 14hS , and a control day , within a potential for 19 EPs . We also measured 24-h HR the third day ( D3 ) after both shifts . We measured perceived stress by visual analog scale and the number of life- and -death emergencies . Results The 17 EPs completing the whole protocol reached maximal HR ( 180.9 ± 6.9 bpm ) during both shifts . Minutes of tachycardia > 100 bpm were higher in 24hS ( 208.3 ± 63.8 ) than in any other days ( 14hS : 142.3 ± 36.9 ; D3/14hS : 64.8 ± 31.4 ; D3/24hS : 57.6 ± 19.1 ; control day : 39.2 ± 11.6 min , p < .05 ) . Shifts induced a cardiac strain twice higher than in days not involving patients contact . Each life- and -death emergency enhanced 26 min of tachycardia ≥100 bpm ( p < .001 ) , 7 min ≥ 110 bpm ( p < .001 ) , 2 min ≥ 120 bpm ( p < .001 ) and 19 min of cardiac strain ≥30 % ( p = .014 ) . Stress was associated with greater duration of tachycardia ≥100 , 110 and 120 bpm , and of cardiac strain ≥30 % ( p < .001 ) . Conclusion We demonstrated several incidences of maximal HR during shifts combined with a high cardiac strain . Duration of tachycardia were the highest in 24hS and lasted several hours . Such values are comparable to those of workers exposed to high physical dem and ing tasks or heat . Therefore , we suggest that EPs limit their exposure to 24hS. We , furthermore , demonstrated benefits of HR monitoring for identifying stressful events . Clinical Trials.gov identifier : NCT01874704 Background The study investigated the extent to which approaches to work , workplace climate , stress , burnout and satisfaction with medicine as a career in doctors aged about thirty are predicted by measures of learning style and personality measured five to twelve years earlier when the doctors were applicants to medical school or were medical students . Methods Prospect i ve study of a large cohort of doctors . The participants were first studied when they applied to any of five UK medical schools in 1990 . Postal question naires were sent to all doctors with a traceable address on the current or a previous Medical Register . The current question naire included measures of Approaches to Work , Workplace Climate , stress ( General Health Question naire ) , burnout ( Maslach Burnout Inventory ) , and satisfaction with medicine as a career and personality ( Big Five ) . Previous question naires had included measures of learning style ( Study Process Question naire ) and personality . Results Doctors ' approaches to work were predicted by study habits and learning styles , both at application to medical school and in the final year . How doctors perceive their workplace climate and workload is predicted both by approaches to work and by measures of stress , burnout and satisfaction with medicine . These characteristics are partially predicted by trait measures of personality taken five years earlier . Stress , burnout and satisfaction also correlate with trait measures of personality taken five years earlier . Conclusions Differences in approach to work and perceived workplace climate seem mainly to reflect stable , long-term individual differences in doctors themselves , reflected in measures of personality and learning style BACKGROUND To examine the mortality pattern of Danish doctors for the period 1973 - 1992 . METHODS A historical prospect i ve cohort study based on the membership register of the Danish Medical Association . The study population consisted of 21,943 medical doctors , 6012 of whom were women . The doctors ' cause-specific mortality was compared with that of the general population . RESULTS The study covered about 277,000 person-years . A total of 2387 deaths occurred from 1 January 1973 to 31 December 1992 . The doctors ' mortality was lower than that of the general population . Both sexes showed a st and ardized mortality ratio ( SMR ) below one for cancer , circulatory diseases and other natural causes . Mortality due to lung cancer was particularly low . The SMR for suicide was significantly increased , 1.6 for males ( 95 % CI : 1.4 - 1.9 ) and 1.7 for females ( 95 % CI : 1.1 - 2.5 ) . The suicide rate was increased , in particular because of an increased number of suicides by poisoning . In addition female doctors displayed a relatively high mortality due to accidents and other types of violent death . CONCLUSIONS Compared with the general population the doctors ' mortality was low , but the mortality from external causes was increased , mainly due to an excess number of suicides Abstract OBJECTIVE : To assess the association between HMO practice , time pressure , and physician job satisfaction . DESIGN : National r and om stratified sample of 5,704 primary care and specialty physicians in the United States . Surveys contained 150 items reflecting 10 facets ( components ) of satisfaction in addition to global satisfaction with current job , one ’s career and one ’s specialty . Linear regression-modeled satisfaction ( on 1–5 scale ) as a function of specialty , practice setting ( solo , small group , large group , academic , or HMO ) , gender , ethnicity , full-time versus part-time status , and time pressure during office visits . “ HMO physicians ” ( 9 % of total ) were those in group or staff model HMOs with > 50 % of patients capitated or in managed care . RESULTS : Of the 2,326 respondents , 735 ( 32 % ) were female , 607 ( 26 % ) were minority ( adjusted response rate 52 % ) . HMO physicians reported significantly higher satisfaction with autonomy and administrative issues when compared with other practice types ( moderate to large effect sizes ) . However , physicians in many other practice setting s averaged higher satisfaction than HMO physicians with re sources and relationships with staff and community ( small to moderate effect sizes ) . Small and large group practice and academic physicians had higher global job satisfaction scores than HMO physicians ( P<.05 ) , and private practice physicians had quarter to half the odds of HMO physicians of intending to leave their current practice within 2 years ( P<.05 ) . Time pressure detracted from satisfaction in 7 of 10 satisfaction facets ( P<.05 ) and from job , career , and specialty satisfaction ( P<.01 ) . Time allotted for new patients in HMOs ( 31 min ) was less than that allotted in solo ( 39 min ) and academic practice s ( 44 min ) , while 83 % of family physicians in HMOs felt they needed more time than allotted for new patients versus 54 % of family physicians in small group practice s ( P<.05 after Bonferroni ’s correction ) . CONCLUSIONS : HMO physicians are generally less satisfied with their jobs and more likely to intend to leave their practice s than physicians in many other practice setting s. Our data suggest that HMO physicians ’ satisfaction with staff , community , re sources , and the duration of new patients visits should be assessed and optimized . Whether providing more time for patient encounters would improve job satisfaction in HMOs or other practice setting s remains to be determined Background Emergency physicians are exposed to greater stress during a 24-hour shift ( 24 hS ) than a 14-hour night shift ( 14 hS ) , with an impact lasting several days . Interleukin-8 ( IL-8 ) is postulated to be a chronic stress biomarker . However , no studies have tracked IL-8 over several shifts or used it for monitoring short-term residual stress . The IL-8 response to the shifts may also increase with age . Conveniently , IL-8 can be measured non-intrusively from urine . Methods We conducted a shifts-r and omized trial comparing 17 emergency physicians ’ urinary IL-8 levels during a 24 hS , a 14 hS , and a control day ( clerical work on return from leave ) . Mean levels of IL-8 were compared using a Wilcoxon matched-pairs test . Independent associations of key factors including shifts , stress , and age with IL-8 levels were further assessed in a multivariable generalized estimating equations model . Results Mean urinary IL-8 levels almost doubled during and after a 24 hS compared with a 14 hS or a control day . Furthermore , IL-8 levels failed to return to control values at the end of the third day after the shift despite a rest day following the 24 hS. In the multivariable model , engaging in a 24 hS , self-reported stress , and age were independently associated with higher IL-8 levels . A 24 hS significantly increased IL-8 levels by 1.9 ng ( p = .007 ) . Similarly , for every unit increase in self-reported stress , there was a 0.11 ng increase in IL-8 levels ( p = .003 ) ; and for every one year advance in age of physicians , IL-8 levels also increased by 0.11 ng ( p = .018 ) . Conclusion The 24 hS generated a prolonged response of the immune system . Urinary IL-8 was a strong biomarker of stress under intensive and prolonged dem and s , both acutely and over time . Because elevated IL-8 levels are associated with cardiovascular disease and negative psychological consequences , we suggest that emergency physicians limit their exposure to 24 hS , especially with advancing age Objectives Appropriate reporting is central to the application of findings from research to clinical practice . The Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) recommendations consist of a checklist of 22 items that provide guidance on the reporting of cohort , case – control and cross-sectional studies , in order to facilitate critical appraisal and interpretation of results . STROBE was published in October 2007 in several journals including The Lancet , BMJ , Annals of Internal Medicine and PLoS Medicine . Within the framework of the revision of the STROBE recommendations , the authors examined the context and circumstances in which the STROBE statement was used in the past . Design The authors search ed the Web of Science data base in August 2010 for articles which cited STROBE and examined a r and om sample of 100 articles using a st and ardised , piloted data extraction form . The use of STROBE in observational studies and systematic review s ( including meta-analyses ) was classified as appropriate or inappropriate . The use of STROBE to guide the reporting of observational studies was considered appropriate . Inappropriate uses included the use of STROBE as a tool to assess the method ological quality of studies or as a guideline on how to design and conduct studies . Results The authors identified 640 articles that cited STROBE . In the r and om sample of 100 articles , about half were observational studies ( 32 % ) or systematic review s ( 19 % ) . Comments , editorials and letters accounted for 15 % , method ological articles for 8 % , and recommendations and narrative review s for 26 % of articles . Of the 32 observational studies , 26 ( 81 % ) made appropriate use of STROBE , and three uses ( 10 % ) were considered inappropriate . Among 19 systematic review s , 10 ( 53 % ) used STROBE inappropriately as a tool to assess study quality . Conclusions The STROBE reporting recommendations are frequently used inappropriately in systematic review s and meta-analyses as an instrument to assess the method ological quality of observational studies OBJECTIVE Physician job satisfaction has been the subject of much research . However , no studies have been conducted comparing academic and private practice physician satisfaction in obstetrics and gynecology . This study was undertaken to measure satisfaction levels for academic and private practice obstetrician-gynecologists and compare different aspects of their practice that contributed to their satisfaction . STUDY DESIGN A survey was mailed to r and omly selected obstetrician-gynecologists in Memphis , TN ; Birmingham , AL ; Little Rock , AR ; and Jackson , MS . Physicians were asked to respond to questions concerning demographics and career satisfaction . They were also asked to assess the contribution of 13 different aspects of their practice in contributing to their job selection and satisfaction using a Likert scale . A score of 1 meant the physician completely disagreed with a statement regarding a factor 's contribution or was completely dissatisfied ; a score of 5 meant the physician completely agreed with a factor 's contribution or was completely satisfied . Simple descriptive statistics , as well as the 2- sample t test , were used . Likert scale values were assumed to be interval measurements . RESULTS Of the 297 question naires mailed , 129 ( 43 % ) physicians responded . Ninety-five ( 74 % ) respondents rated their overall satisfaction as 4 or 5 . No significant difference was found between academic and private physicians when comparing overall job satisfaction ( P = .25 ) . When compared to private practice physicians , the aspects most likely contributing to overall job satisfaction for academic physicians were the ability to teach , conduct research , and practice variety ( P = .0001 , P = .0001 , and P = .007 , respectively ) . When compared with academic physicians , the aspects most likely contributing to job satisfaction for private practice physicians were autonomy , physician-patient relationship , and insurance reimbursement ( P = .0058 , P = .0001 , and P = .0098 , respectively ) . When choosing a practice setting , academic physicians found variety , teaching , and research to be more important ( P = .0027 , P = .0001 , and P = .0001 , respectively ) . In contrast , private practice physicians found autonomy , physician-patient relationship , coworkers , and geographic location to be more important ( P = .0005 , P = .0001 , P = .0035 , and P = .0016 , respectively ) . CONCLUSION Academic and private practice physicians are equally satisfied with their careers . However , teaching , research and variety contribute more to academic satisfaction , whereas autonomy , physician-patient relationship , and coworkers contribute more to satisfaction for the physician in private practice . This study may be used when counseling residents concerning their career options OBJECTIVE --To identify sources of job stress associated with high levels of job dissatisfaction and negative mental wellbeing among general practitioners in Engl and . DESIGN --Multivariate analysis of large data base of general practitioners compiled from results of confidential question naire survey . Data obtained on independent variables of job stress , demographic factors , and personality . Dependent variables were mental health , job satisfaction , alcohol consumption , and smoking . SETTING --National sample of general practitioners studied by university department of organisational psychology . SUBJECTS -- One thous and eight hundred seventeen general practitioners selected at r and om by 20 family practitioner committees in Engl and . INTERVENTIONS --None . END POINT -- Determination of the combination of independent variables that were predictive of mental health and job satisfaction . MEASUREMENTS AND MAIN RESULTS --Women general practitioners both had job satisfaction and showed positive signs of mental wellbeing in contrast with other normative groups . Conversely , male doctors showed significantly higher anxiety scores than the norms , had less job satisfaction , and drank more alcohol than their women counterparts . Multivariate analysis disclosed four job stressors that were predictive of high levels of job dissatisfaction and lack of mental wellbeing ; these were dem and s of the job and patients ' expectations , interference with family life , constant interruptions at work and home , and practice administration . CONCLUSIONS --There may be substantial benefit in providing a counselling service for general practitioners and other health care workers who suffer psychological pressure from their work |
2,286 | 29,171,340 | Good discriminative validity was found between playing levels and ages .
The LSPT was positively correlated with sprint , dribbling , and agility test ; however , a weak correlation was established with in-game performance .
The findings indicate that the LSPT has acceptable test-retest reliability and discriminative validity .
However , it may not be a feasible and effective way to interpret the intra-individual change of skill performance in practice . | ABSTRACT The purpose of this paper was to systematic ally review the literature and examine the research method ological quality , measurement properties and feasibility of the Loughborough Soccer Passing Test ( LSPT ) . | To examine the effects of aerobic interval training on the decline in short-passing ability caused by a short bout of high-intensity intermittent activities . For this r and omized controlled trial , 26 junior soccer players ( mean age , 17.8 + /- 0.6 years ; mean height , 178 + /- 5 cm ; mean body mass , 74.5 + /- 6.9 kg ) were recruited . After baseline measurements , subjects were r and omly allocated to 1 of 2 groups : the control group ( CG ) or the aerobic interval training group ( ITG ) . The ITG completed 4 weeks of high-intensity aerobic training , consisting of 4 bouts of running for 4 min at 90%-95 % of maximal heart rate , with 3 min of active recovery between sets , in addition to normal training . Maximum oxygen uptake , Yo-Yo Intermittent Recovery Test level 1 ( YYIRT ) , and short-passing ability ( measured using the Loughborough Soccer Passing Test ( LSPT ) ) were measured before and after a 5 min high-intensity simulation ( HIS ) , reproducing the most intense phase of a match . The ITG ( n = 11 ) , but not the CG ( n = 10 ) , showed a significant 12 % and 4 % increase in YYIRT and maximal oxygen consumption after training , respectively , and reduced the worsening in LSPT penalty time after the HIS ( p < 0.05 ) . The relative exercise intensity during HIS decreased in the ITG only ( p < 0.01 ) . Our results demonstrated that junior soccer players may benefit from aerobic training to attenuate the decline in short-passing ability caused by a short bout of intermittent activities completed at the same pretraining workload The effects of high-intensity , short- duration , re-warm-ups on team-sport-related performance were investigated . In a r and omised , cross-over study , participants performed 2 × 26-min periods of an intermittent activity protocol ( IAP ) on a non-motorized treadmill , interspersed by 15-min of passive recovery ( CON ) ; 3-min small-sided game ( SSG ) ; or a 5RM leg-press . Measures included counter-movement jump , repeated-sprint , the Loughborough soccer passing test ( LSPT ) , blood lactate concentration , heart-rate , and perceptual measures . Data were analyzed using effect size ( 90 % confidence intervals ) , and percentage change ; determining magnitudes of effects . A 5RM re-warm-up improved flight-time to contraction-time ratio when compared to SSG ( 9.8 % , ES ; 0.5±0.3 ) and CON ( ES : 9.4 % , 0.7±0.5 ) re-warm-ups , remaining higher following the second IAP ( 8.8 % , ES ; 0.5±0.3 and 10.2 % , ES ; 0.6±0.6 , respectively ) . Relative-maximum rate-of-force development was greater in the 5RM condition following the second IAP compared to SSG ( 29.3 % , ES ; 0.7±0.5 ) and CON ( 16.2 % , ES ; 0.6±0.6 ) . Repeated-sprint ability during the second IAP improved in the 5RM re-warm-up ; peak velocity , mean velocity , and acceleration were 4 , 3 , and 18 % greater , respectively . Within groups , the SSG re-warm-up improved LSPT performance post-intervention ; 6.4 % ( ES : 0.6±0.8 ) and following the second IAP 6.2 % ( ES : 0.6±0.6 ) , compared to pre-intervention . A 5RM leg-press re-warm-up improved physical performance , while a SSG re-warm-up enhanced skill execution following st and ardized intermittent exercise The aim of this experiment was to evaluate bilateral motor performance effects from training the non-dominant leg of competitive soccer players . The subjects were 39 soccer players , 15 - 20 years of age , performance-matched and r and omly divided into a training group ( n = 18 ) and a control group ( n = 21 ) both belonging to the same team . Both groups were tested by using two st and ardised foot-tapping tests and three soccer-specific tests . The training intervention consisted of the experimental group participating in all parts of their soccer training except full play , using the non-dominant leg for 8 weeks . Statistical analyses for the soccer-specific tests revealed that the experimental group improved significantly as compared to the control group from the pre-test to the post-test period in their use of the trained non-dominant leg . Somewhat unexpectedly , the experimental group also improved significantly in the tests , which made use of the dominant side . The st and ardised foot-tapping tests revealed similar results . The results might be explained by improved generalised motor programmes , or from a Dynamic Systems Approach , indicating that the actual training relates to the h and ling of all the information available to the subject in the situation , and that the body self-organises the motor performance Abstract Reliability refers to the reproducibility of values of a test , assay or other measurement in repeated trials on the same individuals . Better reliability implies better precision of single measurements and better tracking of changes in measurements in research or practical setting s. The main measures of reliability are within-subject r and om variation , systematic change in the mean , and retest correlation . A simple , adaptable form of within-subject variation is the typical ( st and ard ) error of measurement : the st and ard deviation of an individual ’s repeated measurements . For many measurements in sports medicine and science , the typical error is best expressed as a coefficient of variation ( percentage of the mean ) . A biased , more limited form of within-subject variation is the limits of agreement : the 95 % likely range of change of an individual ’s measurements between 2 trials . Systematic changes in the mean of a measure between consecutive trials represent such effects as learning , motivation or fatigue ; these changes need to be eliminated from estimates of within-subject variation . Retest correlation is difficult to interpret , mainly because its value is sensitive to the heterogeneity of the sample of participants . Uses of reliability include decision-making when monitoring individuals , comparison of tests or equipment , estimation of sample size in experiments and estimation of the magnitude of individual differences in the response to a treatment . Reasonable precision for estimates of reliability requires approximately 50 study participants and at least 3 trials . Studies aim ed at assessing variation in reliability between tests or equipment require complex design s and analyses that research ers seldom perform correctly . A wider underst and ing of reliability and adoption of the typical error as the st and ard measure of reliability would improve the assessment of tests and equipment in our disciplines UNLABELLED There is little evidence regarding the benefits of caffeine ingestion on cognitive function and skillful actions during sporting performance , especially in sports that are multifaceted in their physiological , skill , and cognitive dem and s. PURPOSE To examine the influence of caffeine on performance during simulated soccer activity . METHODS Twelve male soccer players completed two 90-min soccer-specific intermittent running trials interspersed with tests of soccer skill ( LSPT ) . The trials were separated by 7 days and adhered to a r and omized crossover design . On each occasion participants ingested 6 mg/kg body mass ( BM ) of caffeine ( CAF ) or a placebo ( PLA ) in a double-blind fashion 60 min before exercise . Movement time , penalties accrued , and total time were recorded for the LSPT . Physiological and performance markers were measured throughout the protocol . Water ( 3 ml/kg BM ) was ingested every 15 min . RESULTS Participants accrued significantly less penalty time in the CAF trial ( 9.7 + /- 6.6 s vs. PLA 11.6 + /- 7.4 s ; p = .02 ) , leading to a significantly lower total time in this trial ( CAF 51.6 + /- 7.7 s vs. PLA 53.9 + /- 8.5 s ; p = .02 ) . This decrease in penalty time was probably attributable to an increased passing accuracy in the CAF trial ( p = .06 ) . Jump height was 2.7 % ( + /- 1.1 % ) higher in the CAF trial ( 57.1 + /- 5.1 cm vs. PLA 55.6 + /- 5.1 cm ; p = .01 ) . CONCLUSIONS Caffeine ingestion before simulated soccer activity improved players ' passing accuracy and jump performance without any detrimental effects on other performance parameters PURPOSE To investigate the effects of mental fatigue on soccer-specific physical and technical performance . METHODS This investigation consisted of two separate studies . Study 1 assessed the soccer-specific physical performance of 12 moderately trained soccer players using the Yo-Yo Intermittent Recovery Test , Level 1 ( Yo-Yo IR1 ) . Study 2 assessed the soccer-specific technical performance of 14 experienced soccer players using the Loughborough Soccer Passing and Shooting Tests ( LSPT , LSST ) . Each test was performed on two occasions and preceded , in a r and omized , counterbalanced order , by 30 min of the Stroop task ( mentally fatiguing treatment ) or 30 min of reading magazines ( control treatment ) . Subjective ratings of mental fatigue were measured before and after treatment , and mental effort and motivation were measured after treatment . Distance run , heart rate , and ratings of perceived exertion were recorded during the Yo-Yo IR1 . LSPT performance time was calculated as original time plus penalty time . LSST performance was assessed using shot speed , shot accuracy , and shot sequence time . RESULTS Subjective ratings of mental fatigue and effort were higher after the Stroop task in both studies ( P < 0.001 ) , whereas motivation was similar between conditions . This mental fatigue significantly reduced running distance in the Yo-Yo IR1 ( P < 0.001 ) . No difference in heart rate existed between conditions , whereas ratings of perceived exertion were significantly higher at iso-time in the mental fatigue condition ( P < 0.01 ) . LSPT original time and performance time were not different between conditions ; however , penalty time significantly increased in the mental fatigue condition ( P = 0.015 ) . Mental fatigue also impaired shot speed ( P = 0.024 ) and accuracy ( P < 0.01 ) , whereas shot sequence time was similar between conditions . CONCLUSIONS Mental fatigue impairs soccer-specific running , passing , and shooting performance This study aim ed to investigate whether isolated or combined carbohydrate ( CHO ) and caffeine ( CAF ) supplementation have beneficial effects on performance during soccer-related tests performed after a previous training session . Eleven male , amateur soccer players completed 4 trials in a r and omized , double-blind , and crossover design . In the morning , participants performed the Loughborough Intermittent Shuttle Test ( LIST ) . Then , participants ingested ( i ) 1.2 g·kg(-1 ) body mass·h(-1 ) CHO in a 20 % CHO solution immediately after and 1 , 2 , and 3 h after the LIST ; ( ii ) CAF ( 6 mg·kg(-1 ) body mass ) 3 h after the LIST ; ( iii ) CHO combined with CAF ( CHO+CAF ) ; and ( iv ) placebo . All drinks were taste-matched and flavourless . After this 4-h recovery , participants performed a countermovement jump ( CMJ ) test , a Loughborough Soccer Passing Test ( LSPT ) , and a repeated-sprint test . There were no main effects of supplementation for CMJ , LSPT total time , or best sprint and total sprint time from the repeated-sprint test ( p>0.05 ) . There were also no main effects of supplementation for heart rate , plasma lactate concentration , rating of perceived exertion ( RPE ) , pleasure-displeasure , and perceived activation ( p>0.05 ) . However , there were significant time effects ( p<0.05 ) , with heart rate , plasma lactate concentration , RPE , and perceived activation increasing with time , and pleasure-displeasure decreasing with time . In conclusion , isolated and /or combined CHO and CAF supplementation is not able to improve soccer-related performance tests when performed after a previous training session Abstract The purpose of this study was to determine the recovery rate of football skill performance following resistance exercise of moderate or high intensity . Ten elite football players participated in three different trials : control , low-intensity resistance exercise ( 4 sets , 8–10 repetitions/set , 65–70 % 1 repetition maximum [ 1RM ] ) and high-intensity resistance exercise ( 4 sets , 4–6 repetitions/set , 85–90 % 1RM ) in a counterbalanced manner . In each experimental condition , participants were evaluated pre , post , and at 24 , 48 , 72 h post exercise time points . Football skill performance was assessed through the Loughborough Soccer Passing Test , long passing , dribbling , shooting and heading . Delayed onset muscle soreness , knee joint range of motion , and muscle strength ( 1RM ) in squat were considered as muscle damage markers . Blood sample s analysed for creatine kinase activity , C-reactive protein , and leukocyte count . Passing and shooting performance declined ( P < 0.05 ) post-exercise following resistance exercise . Strength declined post-exercise following high-intensity resistance exercise . Both trials induced only a mild muscle damage and inflammatory response in an intensity-dependent manner . These results indicate that football skill performance is minimally affected by acute resistance exercise independent of intensity suggesting that elite players may be able to participate in a football practice or match after only 24 h following a strength training session Abstract In this study , we examined the reliability and construct validity of new soccer skills tests . Twenty soccer players ( 10 professional and 10 recreational ) repeated trials of passing , shooting , and dribbling skills on different days . Passing and shooting skills required players to kick a moving ball , delivered at constant speed , towards one of four r and omly determined targets . Dribbling required players to negotiate seven cones over 20 m. Each trial consisted of 28 passes , 8 shots , and 10 dribbles . Ball speed , precision , and success were determined for all tests using video analysis . Systematic bias was small ( < 9 % in all measures ) and all outcome measures were similar between trials . Test – retest reliability statistics were as follows : ball speed ( passing , shooting , dribbling ; coefficient of variation [ CV ] : 6.5 % , 6.9 % , 2.4 % ; ratio limits of agreement [ RLOA ] : 0.958 ×/÷ 1.091 , 0.990 ×/÷ 1.107 , 0.993 ×/÷ 1.039 ) , precision ( passing , shooting , dribbling ; CV : 10.0 % , 23.5 % , 4.6 % ; RLOA : 0.956 ×/÷ 1.147 , 1.030 ×/÷ 1.356 , 1.000 ×/÷ 1.068 ) , and success ( passing , shooting , dribbling ; CV : 11.7 % , 14.4 % , 2.2 % ; RLOA : 1.017 ×/÷ 1.191 , 0.913 ×/÷ 1.265 , 0.996 ×/÷ 1.035 ) . Professional players performed better than recreational players in at least one outcome measure for all skills . These findings demonstrate the reliability and validity of new soccer skill protocol Abstract The aim of this study was to investigate the effect of ingesting a carbohydrate-electrolyte solution , during the 90-min Loughborough Intermittent Shuttle Test , on soccer skill performance . Seventeen male soccer players ingested either a 6.4 % carbohydrate-electrolyte solution or placebo solution equivalent to 8 ml · kg−1 body mass before exercise and 3 ml · kg−1 body mass after every 15 min of exercise , in a double-blind r and omized cross-over design , with the trials separated by 7 days . The evening before the main trial , the participants performed glycogen-reducing exercise on a cycle ergometer ( 80 min at 70%[Vdot]O2max ) and were then fed a low-carbohydrate meal . After a 12-h overnight fast , they performed The Loughborough Soccer Passing Test before and after every 15 min of exercise . Analysis of the combined skill test data showed a significant time effect ( P = 0.001 ) with differences between 0–45 and 75–90 min ( P < 0.05 ) . There was a 3 % reduction in skill performance from before to after exercise in the carbohydrate-electrolyte trial , whereas in the placebo trial the decrease was 14 % ( P = 0.07 ) . In conclusion , skill performance during the simulated soccer activity appeared to deteriorate in the last 15–30 min of exercise . However , providing 52 g · h−1 carbohydrate during exercise showed a tendency to better maintain soccer skill performance than a taste-matched placebo |
2,287 | 25,992,221 | We provide a critical , non- systematic review of gastric cancer and discuss the role of perioperative radiation therapy in its treatment | Gastric cancer is one of the most common neoplasms and a main cause of cancer-related mortality worldwide .
Surgery remains the mainstay for cure and is considered for all patients with potentially curable disease .
However , despite the fact that surgery alone usually leads to favorable outcomes in early stage disease , late diagnosis usually means a poor prognosis .
In these setting s , multimodal therapy has become the established treatment for locally advanced tumors , while the high risk of locoregional relapse has favored the inclusion of radiotherapy in the comprehensive therapeutic strategy . | PURPOSE The first planned interim analysis ( median follow-up , 3 years ) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival , the primary end point . The results were therefore opened at the recommendation of an independent data and safety monitoring committee . We report 5-year follow-up data on patients enrolled onto the ACTS-GC study . PATIENTS AND METHODS Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were r and omly assigned to receive S-1 after surgery or surgery only . S-1 ( 80 to 120 mg per day ) was given for 4 weeks , followed by 2 weeks of rest . This 6-week cycle was repeated for 1 year . The primary end point was overall survival , and the secondary end points were relapse-free survival and safety . RESULTS The overall survival rate at 5 years was 71.7 % in the S-1 group and 61.1 % in the surgery-only group ( hazard ratio [ HR ] , 0.669 ; 95 % CI , 0.540 to 0.828 ) . The relapse-free survival rate at 5 years was 65.4 % in the S-1 group and 53.1 % in the surgery-only group ( HR , 0.653 ; 95 % CI , 0.537 to 0.793 ) . Subgroup analyses according to principal demographic factors such as sex , age , disease stage , and histologic type showed no interaction between treatment and any characteristic . CONCLUSION On the basis of 5-year follow-up data , postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy Background Radical surgery is the cornerstone in the treatment of resectable gastric cancer . The Intergroup 0116 and MAGIC trials have shown benefit of postoperative chemoradiation and perioperative chemotherapy , respectively . Since these trials can not be compared directly , both regimens are evaluated prospect ively in the CRITICS trial . This study aims to obtain an improved overall survival for patients treated with preoperative chemotherapy and surgery by incorporating radiotherapy concurrently with chemotherapy postoperatively . Methods / design In this phase III multicentre study , patients with resectable gastric cancer are treated with three cycles of preoperative ECC ( epirubicin , cisplatin and capecitabine ) , followed by surgery with adequate lymph node dissection , and then either another three cycles of ECC or concurrent chemoradiation ( 45 Gy , cisplatin and capecitabine ) . Surgical , pathological , and radiotherapeutic quality control is performed . The primary endpoint is overall survival , secondary endpoints are disease-free survival ( DFS ) , toxicity , health-related quality of life ( HRQL ) , prediction of response , and recurrence risk assessed by genomic and expression profiling . Accrual for the CRITICS trial is from the Netherl and s , Sweden , and Denmark , and more countries are invited to participate . Conclusion Results of this study will demonstrate whether the combination of preoperative chemotherapy and postoperative chemoradiotherapy will improve the clinical outcome of the current European st and ard of perioperative chemotherapy , and will therefore play a key role in the future management of patients with resectable gastric cancer . Trial registration clinical trials.gov PURPOSE The Intergroup 0116 trial has demonstrated that postoperative chemoradiotherapy ( CRT ) improves survival in gastric cancer . We retrospectively compared survival and recurrence patterns in two phase I/II studies evaluating more intensified postoperative CRT with those from the Dutch Gastric Cancer Group Trial ( DGCT ) that r and omly assigned patients between D1 and D2 lymphadenectomy . PATIENTS AND METHODS Survival and recurrence patterns of 91 patients with adenocarcinoma of the stomach who had received surgery followed by radiotherapy combined with fluorouracil and leucovorin ( n = 5 ) , capecitabine ( n = 39 ) , or capecitabine and cisplatin ( n = 47 ) were analyzed and compared with survival and recurrence patterns of 694 patients from the DGCT ( D1 , n = 369 ; D2 , n = 325 ) . For both groups , the Maruyama Index of Unresected Disease ( MI ) was calculated and correlated with survival and recurrence patterns . RESULTS With a median follow-up of 19 months in the CRT group , local recurrence rate after 2 years was significantly higher in the surgery only ( DGCT ) group ( 17 % v 5 % ; P = .0015 ) . Separate analysis of CRT patients who underwent a D1 dissection ( n = 39 ) versus DGCT-D1 ( n = 369 ) showed fewer local recurrences after chemoradiotherapy ( 2 % v 8 % ; P = .001 ) , whereas comparison of CRT-D2 ( n = 25 ) versus DGCT-D2 ( n = 325 ) demonstrated no significant difference . CRT significantly improved survival after a microscopically irradical ( R1 ) resection . The MI was found to be a strong independent predictor of survival . CONCLUSION After D1 surgery , the addition of postoperative CRT had a major impact on local recurrence in resectable gastric cancer INTRODUCTION Worldwide , gastric cancer remains one of the most common malignancies . Discouraging survival rates after surgical treatment promote the study of adjuvant therapy . A prospect ively , r and omized , controlled clinical trial was performed in order to determine whether pre-operative and intraoperative radiotherapy improves treatment results of gastrectomy for stomach carcinoma . METHODS From 1993 to 1998 , 112 patients were r and omized and underwent exploratory laparotomy ; among them 78 satisfied protocol requirements and entered in the trial . Patients in the experimental group were treated with pre-operative radiotherapy ( 20 Gy/5 days ) , gastrectomy and intraoperative radiotherapy ( 20 Gy using 8 - 12 electrons ) . Patients in the control group underwent surgery alone . RESULTS Incidence and distribution of post-operative complications were similar in both groups except significantly higher incidence of pancreatitis after surgical treatment . No late radiation-related morbidity was registered . There was no significant difference in survival between the two treatment groups ( Chi(2)=1.026 , df=1 , P=0 . 311 ) as well as in N0 ( Chi(2)=0.0029 , df=1 , P=0.956 ) and T1 - 2 subgroups ( Chi(2)=0.1928 , df=1 , P=0.660 ) . In contrast , combined treatment had marked survival advantage in more advanced stages : in the case of lymph-node involvement ( Chi(2)=4.19 , df=1 , P=0.04 ) and extragastric tumour extension ( Chi(2)=4.118 , df=1 , P=0.042 ) . CONCLUSION The proposed intensive treatment programme is feasible , shows good acute and late tolerance and has the potential to improve survival in patients with locally advanced gastric cancer PURPOSE Preoperative chemotherapy is an accepted st and ard in the treatment of localized esophagogastric adenocarcinoma . Adding radiation therapy to preoperative chemotherapy appears promising , but its definitive value remains unknown . PATIENTS AND METHODS Patients with locally advanced ( uT3 - 4NXM0 ) adenocarcinoma of the lower esophagus or gastric cardia were r and omly allocated to one of two treatment groups : induction chemotherapy ( 15 weeks ) followed by surgery ( arm A ) ; or chemotherapy ( 12 weeks ) followed by chemoradiotherapy ( 3 weeks ) followed by surgery ( arm B ) . Primary outcome was overall survival time . A total of 354 patients were needed to detect a 10 % increase in 3-year survival from 25 % to 35 % by addition of radiation therapy . The study was prematurely closed due to low accrual . RESULTS The median observation time was 46 months . A total of 126 patients were r and omly assigned and 119 eligible patients were evaluated . The number of patients undergoing complete tumor resection was not different between treatment groups ( 69.5 % v 71.5 % ) . Patients in arm B had a significant higher probability of showing pathologic complete response ( 15.6 % v 2.0 % ) or tumor-free lymph nodes ( 64.4 % v 37.7 % ) at resection . Preoperative radiation therapy improved 3-year survival rate from 27.7 % to 47.4 % ( log-rank P = .07 , hazard ratio adjusted for r and omization strata variables 0.67 , 95 % CI , 0.41 to 1.07 ) . Postoperative mortality was nonsignificantly increased in the chemoradiotherapy group ( 10.2 % v 3.8 % ; P = .26 ) . CONCLUSION Although the study was closed early and statistical significance was not achieved , results point to a survival advantage for preoperative chemoradiotherapy compared with preoperative chemotherapy in adenocarcinomas of the esophagogastric junction BACKGROUND AND PURPOSE The role of postoperative chemoradiotherapy in the treatment of patients with gastric cancer with D2 lymph node curative dissection is not well established . In this study , we compared postoperative intensity-modulated radiotherapy plus chemotherapy ( IMRT-C ) with chemotherapy-only in this patient population . MATERIAL S AND METHODS We r and omly assigned patients with D2 lymph node dissection in gastric cancer to IMRT-C or chemotherapy-only groups . The adjuvant IMRT-C consisted of 400 mg of fluorouracil per square meter of body-surface area per day plus 20 mg of leucovorin per square meter of body-surface area per day for 5 days , followed by 45 Gy of IMRT for 5 weeks , with fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy . Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the completion of IMRT . Chemotherapy-only group was given the same chemotherapy regimens as IMRT-C group . RESULTS The median overall survival ( OS ) in the chemotherapy-only group was 48 months , as compared with 58 months in the IMRT-C group ; the hazard ratio for death was 1.24 ( 95 % confidence interval , 0.94 - 1.65 ; P=0.122 ) . IMRT-C was associated with increases in the median duration of recurrence-free survival ( RFS ) ( 36 months vs. 50 months ) , the hazard ratio for recurrence was 1.35 ( 95 % confidence interval , 1.03 - 1.78 ; P=0.029 ) . COX multivariate regression analysis showed that lymph node metastasis and TNM stage were both the independent prognostic factors . Rates of all grade adverse events were similar in the two treatment groups . CONCLUSIONS IMRT-C improved RFS , but did not significantly improve OS among patients with D2 lymph node dissection in gastric cancer . Using IMRT plus chemotherapy was feasible and well tolerated in patients with gastric cancer after D2 resection Sixty-two patients with resectable but poor-prognosis gastric carcinoma were r and omized to either no surgical adjuvant therapy or treatment with 5-fluorouracil ( 15 mg/kg by rapid intravenous injection X 3 ) plus radiation ( 3,750 rad in 24 fractions ) initiated 3 1/2 to six weeks postoperatively . Informed consent was obtained after r and omization and only from the 39 r and omized to treatment . Ten patients refused their treatment assignment . The five-year survival rate for patients r and omized to treatment was 23 % , and for those r and omized to no treatment , 4 % ( P less than .05 ) . Both the survival distributions and the alive-without-recurrence distributions were significantly different for the two groups ( P = .024 ) and favored treatment assignment . When the treatment assignment group was broken down to those patients actually receiving treatment and those refusing , five-year survival rates were : treated , 20 % ; treatment refusal , 30 % ; controls , 4 % ; the three survival distributions were not significantly different . Thirty-nine percent of patients actually treated had a local-regional component of first clinical recurrence compared with 54 % of those who received no treatment . This study does not establish 5-fluorouracil plus radiation as effective surgical adjuvant therapy for gastric cancer but suggests this approach as a possible fruitful area for continued research . This study also illustrates the potential problems that may be encountered in interpreting results when patients are r and omized to a study before consent is obtained BACKGROUND Adjuvant chemoradiotherapy does not represent the st and ard of care in patients with resected high-risk gastric cancer ; however , results from phase 2 and r and omized trials suggest improvement in overall survival . We assessed the feasibility and toxic effects of chemoradiotherapy as adjuvant treatment in locally advanced gastric cancer . DESIGN Pilot study . SETTING University hospital . PATIENTS Twenty-nine patients with T4N+ or any TN23 gastric cancer previously treated with potentially curative surgery were enrolled . All of the patients received combined adjuvant chemotherapy with FOLFOX-4 ( ie , a combination of folinic acid [ leucovorin ] , fluorouracil , and oxaliplatin [ Eloxatin ] ) for 8 cycles and concomitant radiotherapy ( 45 Gy in 25 daily fractions over 5 weeks ) . Radiotherapy was begun after the first 2 cycles of FOLFOX-4 , which was reduced by 25 % during the period of concomitant radiotherapy . MAIN OUTCOME MEASURES Treatment toxic effects according to the National Cancer Institute-Common Toxicity Criteria classification , overall and disease-free survival rates , and identification of prognostic indicators . RESULTS All of the patients completed treatment . Severe hematologic and gastrointestinal toxic effects occurred in 10 % and 33 % , respectively . No acute hepatic or renal toxic effects were observed ; 1 patient experienced severe neurotoxicity . Disease-free and overall survival rates at 1 , 2 , and 3 years were 79 % , 35 % , and 35 % and 85 % , 62.6 % , and 50.1 % , respectively , and were shown to be substantially better than those observed in untreated patients . Long-term outcome was related to TNM stage , basal serum tumor marker level , and , particularly , lymph node ratio . CONCLUSION A multimodal approach with FOLFOX-4 and radiotherapy is feasible and effective for the treatment of patients with resected high-risk gastric cancer The optimal adjuvant treatment for gastric cancer remains controversial . We compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen , in patients with high-risk gastric cancer , with that of the same chemotherapy plus radiation therapy ( RT ) . In addition , we evaluated the prognostic and /or predictive value of a panel of molecular markers . Patients with histologically proven , radically resected gastric cancer , stage ≥T3 and /or N+ were r and omized to 6 cycles of docetaxel with cisplatin , both at 75 mg/m2 every 3 weeks ( arm A ) or the same treatment with RT ( arm B ; 45 Gy ) . Due to excessive nausea and vomiting , cisplatin was substituted by carboplatin at AUC ( area under the curve ) of 5 after the first 45 patients ( 22 group A , 23 group B ) . The prognostic value of EGFR , ERCC1 , HER2 , MET/HGFR , MAP-Tau , and PTEN expression was also studied in a subset of 67 patients using immunohistochemistry on tissue microarrays ( TMAs ) . A total of 147 patients were r and omized . After a median follow-up of 53.7 months , no differences in overall ( OS ) and disease-free survival ( DFS ) were found between the two arms . The most common grade 3/4 toxicities for arms A and B ( excluding alopecia ) were non-febrile neutropenia ( 11 and 17 % , respectively ) , febrile neutropenia ( 9 and 7 % ) and diarrhea ( 7 and 4 % , respectively ) . Patients with ERCC1 positive tumors had significantly longer median DFS ( 33.1 vs. 11.8 months , Wald P = 0.016 ) and OS ( 63.2 vs. 18.8 months , Wald P = 0.046 ) . Our results indicate that the addition of RT to platinum/docetaxel adjuvant chemotherapy does not appear to improve survival in high-risk , radically resected gastric cancer . However , the possibility that a benefit by the addition of RT was not detected due to decreased power of the study should not be excluded A prospect i ve , r and omised controlled trial of surgery , surgery with adjuvant radiotherapy and surgery with adjuvant chemotherapy ( 5-fluorouracil , adriamycin and mitomycin C ) in operable gastric cancer is described . Four hundred and thirty-six patients were r and omly allocated to one of three treatment groups . With 12 months ' minimum follow-up , 334 patients have died , 292 from recurrent cancer . The median survival for all patients was 15 months . Neither form of adjuvant therapy provides any survival advantage . Surgery remains the principal treatment for operable gastric cancer . Care should be taken to st and ardise surgical treatment and any adjuvant treatments must be compared within the confines of controlled , r and omised trials PURPOSE An attempt was made to define the role of radiotherapy before operation for AGC . METHODS AND MATERIAL S From January 1978 to May 1989 , a prospect i ve r and omized trial on preoperative radiotherapy ( R+S ) vs. surgery alone ( S ) for AGC was carried out in 370 patients . Patients were r and omized into a combined group ( R+S , 171 patients ) or a surgery alone group ( S , 199 patients ) by the envelope method . 8-MV photon or telecobalt was used for the preoperative radiation therapy , using anterior-posterior opposing parallel fields to deliver 40 Gy to the cardia , lower segment of the esophagus , fundus , lesser curvature , and hepatogastric ligament . Surgery was performed after 2 to 4 weeks rest . RESULTS The 5- and 10-year survival rates of the R+S Group and the S Alone Group were 30.10 % and 19.75 % , 20.26 % and 13.30 % , respectively . The survival curves of these two groups diverged right from the beginning after the operation over the ninth year . Statistics by Kaplan-Meier log rank test proves that the difference is significant ( chi2 = 6.74 , p = 0.0094 ) . The immediate results were : resection rate 89.5 % and 79.4 % ( p < 0.01 ) ; pathologic stage after resection T2 12.9 % and 4.5 % ( p < 0.01 ) , T4 40.3 % and 51.3 % ( p < 0.05 ) , lymph node metastasis rates 64.3 % and 84.9 % ( p < 0.001 ) ; operative mortality rates 0.6 % and 2.5 % ; intrathoracic leak rates 1.8 % and 4.0 % , respectively . The causes of failure were : local uncontrol and recurrence 38.6 % vs. 51.7 % ( p < 0.025 ) , regional lymph node metastasis 38.6 % vs. 54.6 % ( p < 0.005 ) , distant metastasis 24.3 % vs. 24.7 % . CONCLUSION Preoperative radiation therapy is able to improve the results of surgery for adenocarcinoma of the gastric cardia PURPOSE Preoperative therapy for localized gastric cancer has considerable appeal . We hypothesized that , in a cooperative group setting , preoperative chemoradiotherapy would induce a 20 % pathologic complete response ( pathCR ) rate . Combined-modality therapy quality , survival , and safety were secondary end points . PATIENTS AND METHODS Patients with localized gastric adenocarcinoma were eligible . A negative laparoscopic evaluation was required . Patients received two cycles of induction fluorouracil , leucovorin , and cisplatin followed by concurrent radiation and chemotherapy ( infusional fluorouracil and weekly paclitaxel ) . Resection was attempted 5 to 6 weeks after chemoradiotherapy was completed . Quality of therapy was assessed with other end points . RESULTS Twenty institutions participated . Forty-nine patients were entered and 43 were assessable ( 12 % stage IB ; 37 % stage II ; and 52 % stage III ) . The pathCR and R0 resection rates were 26 % and 77 % , respectively . At 1 year , more patients with pathCR ( 82 % ) are living than those with less than pathCR ( 69 % ) . Grade 4 toxicity occurred in 21 % of patients . Chemotherapy , radiotherapy , and surgery per protocol ( including acceptable variations ) occurred in 98 % , 44 % , and 63 % of patients , respectively . A D2 dissection was performed in 50 % of patients . Of 18 major radiotherapy variations , 17 were due to the lack of inclusion of the L3 - 4 vertebral interphase as prespecified . CONCLUSION For localized gastric cancer , preoperative chemoradiotherapy strategy achieved a pathCR rate of more than 20 % in a cooperative group setting . The quality of surgery improved ( 50 % with D2 dissection ) possibly because surgery was part of this trial . With some refinements , this preoperative chemoradiotherapy strategy is poised for a r and omized comparison with postoperative adjuvant chemoradiotherapy in patients with gastric cancer PURPOSE Surgical resection of gastric cancer has produced suboptimal survival despite multiple r and omized trials that used postoperative chemotherapy or more aggressive surgical procedures . We performed a r and omized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure ( LRF ) following surgery . We originally reported results with 4-year median follow-up . This up date , with a more than 10-year median follow-up , presents data on failure patterns and second malignancies and explores selected subset analyses . PATIENTS AND METHODS In all , 559 patients with primaries ≥ T3 and /or node-positive gastric cancer were r and omly assigned to observation versus radiochemotherapy after R0 resection . Fluorouracil and leucovorin were administered before , during , and after radiotherapy . Radiotherapy was given to all LRF sites to a dose of 45 Gy . RESULTS Overall survival ( OS ) and relapse-free survival ( RFS ) data demonstrate continued strong benefit from postoperative radiochemotherapy . The hazard ratio ( HR ) for OS is 1.32 ( 95 % CI , 1.10 to 1.60 ; P = .0046 ) . The HR for RFS is 1.51 ( 95 % CI , 1.25 to 1.83 ; P < .001 ) . Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse . Second malignancies were observed in 21 patients with radiotherapy versus eight with observation ( P = .21 ) . Subset analyses show robust treatment benefit in most subsets , with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect . CONCLUSION Intergroup 0116 ( INT-0116 ) demonstrates strong persistent benefit from adjuvant radiochemotherapy . Toxicities , including second malignancies , appear acceptable , given the magnitude of RFS and OS improvement . LRF reduction may account for the majority of overall relapse reduction . Adjuvant radiochemotherapy remains a rational st and ard therapy for curatively resected gastric cancer with primaries T3 or greater and /or positive nodes PURPOSE The INT0116 study has established postoperative chemoradiotherapy as the st and ard of care for completely resected gastric adenocarcinoma . However , the optimal chemoradiation regimen remains to be defined . We conducted a prospect i ve , multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery . METHODS AND MATERIAL S Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible . Adjuvant therapy consisted of one cycle of epirubicin , cisplatin , and 5-FU ( ECF ) , followed by radiotherapy with concurrent infusional 5-FU , and then two additional cycles of ECF . Radiotherapy was delivered using precisely defined , multiple-field , three-dimensional conformal techniques . RESULTS A total of 54 assessable patients were enrolled from 19 institutions . The proportion of patients commencing Cycles 1 , 2 , and 3 of ECF chemotherapy were 100 % , 81 % , and 67 % respectively . In all , 94 % of patients who received radiotherapy completed treatment as planned . Grade 3/4 neutropenia occurred in 66 % of patients with 7.4 % developing febrile neutropenia . Most neutropenic episodes ( 83 % ) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF . Grade 3/4 gastrointestinal toxicity occurred in 28 % of patients . In all , 35 % of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended before commencement of treatment . At median follow-up of 36 months , the 3-year overall survival rate was estimated at 61.6 % . CONCLUSIONS This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting . A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored , r and omized Phase III trial PURPOSE The Intergroup 0116 ( INT 0116 ) trial demonstrated a survival benefit for a broad group of fully resected gastric cancer patients . This study examined the impact on survival of the release of this l and mark trial . METHODS AND MATERIAL S Patients with gastric carcinoma diagnosed between 1995 and 2004 were identified in the Surveillance , Epidemiology , and End Results ( SEER ) data base . Patients from the overall population as well as those potentially eligible for the INT 0116 trial were classified as having been diagnosed either before ( 1995 - 1999 ) or after ( 2000 - 2004 ) this trial . Both Kaplan-Meier survival analysis and Cox models were used to examine survival trends within these cohorts . RESULTS For the overall population of 22,982 patients , the use of radiotherapy ( RT ) significantly changed after the INT 0116 trial ( p < 0.0001 ) , with postoperative RT increasing from 6.5 % to 13.3 % . For the two periods of interest , overall survival significantly improved in recent years ( p = 0.00008 ) . A similar improvement was also seen for patients who were potentially eligible for the INT 0116 trial ( p = 0.004 ) , with 3-year survival rates improving from 32.2 % to 34.5 % . On both univariate and multivariate analysis , use of RT was associated with a significant survival improvement ( HR , 0.65 [ 0.48 - 0.88 ] ; p = 0.005 ) . CONCLUSION Use of postoperative RT for gastric cancer has significantly increased after the release of the INT 0116 trial , likely reflecting increased use of adjuvant chemoradiotherapy . This change has been associated with improved survival in gastric cancer patients , suggesting that the improved outcome seen in this trial has been successfully translated to the community The overall survival in patients with gastric cancer is low , even among those undergoing resection . It has been hoped that the development of adjuvant therapy might improve survival in patients following surgery when tumour burden was minimal and both chemotherapy and radiotherapy have been proposed as suitable for use in gastric cancer . Their value has been evaluated by the British Stomach Cancer Group Second adjuvant therapy trial . 436 patients entered a prospect i ve , r and omised , controlled trial of adjuvant radiotherapy or cytotoxic chemotherapy with mitomycin , doxorubicin , and fluorouracil after gastrectomy for adenocarcinoma . After at least 5 years , there have been 372 deaths of which 7 were due to surgical complications and 327 from recurrent cancer . Following stratified r and omisation , 145 patients were allocated to surgery alone , 153 to receive adjuvant radiotherapy , and 138 to adjuvant combination chemotherapy . The overall 2-year and 5-year survival were 33 % ( 95 % confidence interval 31 - 35 % ) and 17 % ( 13 - 21 % ) . No survival advantage has been shown for those patients receiving either adjuvant therapy compared to those undergoing surgery alone . The 5-year survival for surgery alone was 20 % , for surgery plus radiotherapy 12 % , and for surgery plus chemotherapy 19 % . Surgery , therefore , remains the st and ard treatment for this condition and the use of adjuvant treatments should be restricted to controlled trials 4003 Background : Following curative resection of gastric or GEJ adenocarcinoma , INT-0116 demonstrated superior survival for pts who received postoperative bolus 5-FU and leucovorin ( LV ) before and after concomitant 5-FU and RT compared to surgery alone . We assessed whether a postoperative chemoRT regimen that replaces 5-FU/LV with a potentially more active systemic therapy ( ECF ) improves overall survival ( OS ) . METHODS Patients with resected gastric or GEJ adenocarcinoma were r and omly assigned to either : Arm A : 1 cycle of 5-FU 425 mg/m2/day plus LV20 mg/m2/day for 5 days/month , followed by 45 Gy ( 1.8 Gy/day ) and concurrent 5-FU ( 200 mg/m2/day CI throughout RT ) , followed by 2 cyclesof 5-FU/LV ; or Arm B : 1 cycle of ECF ( E 50 mg/m2 day 1 , C 60 mg/m2 day 1 , and 5-FU 200 mg/m2/day CI days 1 - 21 ) followed by 45 Gy ( 1.8 Gy/day ) and concurrent 5-FU ( 200 mg/m2/day CI throughout RT ) , followed by 2 cycles of reduced dose of ECF ( E 40 mg/m2 day 1 , C 50 mg/m2 day 1 , and 5-FU 200 mg/m2/day CI days 1 - 21 ) . RESULTS Between 4/03 and 5/09 , 546 pts were enrolled . There were no significant differences between arms with regard to age , sex , race , performance status , T or N stage or extent of lymphadenectomy . Treatment related deaths occurred in 8 ( 3 % ) pts on Arm A ( 5-FU/LV ) and 1 ( < 1 % ) pt on Arm B ( ECF ) . Grade 4 toxicity : 40 % , Arm A v 26 % , Arm B ( p<0.001 ) . Major toxicities ( ≥ gr . 3 ) included : neutropenia ( 53 v 48 % ) , diarrhea ( 15 v 7 % ) , and mucositis ( 15 v 7 % ) for Arms A and B , respectively . With 242 deaths reported , median OS was 37 months in Arm A and 38 months in Arm B ( HR , 1.03 ; 95 % CI , 0.80 - 1.34 ; p=0.80 ) . 3yr-OS was 50 % in Arm A and 52 % in Arm B. Median disease-free survival ( DFS ) was 30 months in Arm A and 28 months in Arm B ( HR , 1.00 ; 95 % CI , 0.79 - 1.27 ; p=0.99 ) . 3yr-DFS was 46 % in Arm A and 47 % in Arm B. CONCLUSIONS Following curative resection of gastric or GEJ adenocarcinoma , postoperative chemoRT using ECF before and after 5-FU/RT does not improve survival when compared to bolus 5-FU/LV before and after 5-FU/RT PURPOSE To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0 ) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection . METHODS AND MATERIAL S The chemotherapy arm received 5 cycles of fluorouracil and leucovorin ( FL ) , and the chemoradiation therapy arm received 1 cycle of FL , then radiation therapy of 45 Gy concurrently with 2 cycles of FL , followed by 2 cycles of FL . Intent-to-treat analysis and per- protocol analyses were performed . RESULTS Between May 6 , 2002 and June 29 , 2006 , a total of 90 patients were enrolled . Forty-four were r and omly assigned to the chemotherapy arm and 46 to the chemoradiation therapy arm . Treatment was completed as planned by 93.2 % of patients in the chemotherapy arm and 87.0 % in the chemoradiation therapy arm . Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival ( LRRFS ) but not disease-free survival . In subgroup analysis for stage III , chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy ( 93.2 % vs 66.8 % , P=.014 ; 73.5 % vs 54.6 % , P=.056 , respectively ) . CONCLUSIONS Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection In order to evaluate the role of adjuvant IORT in the treatment of resectable gastric carcinoma , we carried out a r and omized trial comparing surgery and surgery+adjuvant IORT . The study included 115 patients within a 74-month period , 51 of them received a single application of 28 Gy to the celiac axis . Patients were comparable with regard to age , sex , tumor stage and operative morbidity . The difference in mean survival time ( IORT : 26.9 months vs. non-IORT , 30.8 months ) and tumor-related death in the long-term course ( mean follow-up period 29.2 months ) with 29.4 % ( 15/51 ) in the IORT-treated patients vs. 31.2 % ( 20/64 ) in non-irradiated patients did not reach significance BACKGROUND AND OBJECTIVES The role of radiation therapy in resectable gastric cancer is question able . To study the value of concentrated preoperative radiotherapy , a r and omized clinical trial had been carried out . METHODS From 1974 to 1978 , 152 patients were r and omized and underwent exploratory laparotomy ; in 50 patients curative surgery was not possible , while 102 patients satisfied protocol requirements and entered in the trial . Patients in the experimental group were treated with preoperative radiotherapy ( 20 Gy/5 days ) and subtotal or total gastrectomy . Patients in the control group underwent surgery alone . RESULTS Study showed acceptable tolerance of radiotherapy regime with no increase of postoperative mortality and morbidity . There was no significant difference in survival between the two treatment groups ( chi 2 = 0.349 , df = 1 , P = 0.555 ) . Subset analysis also failed to demonstrate significant survival advantages of the combined treatment ; however , some positive trends were seen in patients with locally advanced gastric cancer . CONCLUSIONS Concentrated preoperative radiotherapy in the dose of 20 Gy is safe and feasible , but seems to be insufficient to improve survival in gastric cancer patients . However , the results are promising in selected subgroups of patients , which encourages future trials with adjuvant radiation therapy OBJECTIVE In 1986 a prospect i ve multicenter observation trial in patients with resected gastric cancer was initiated in Germany . An analysis of prognostic factors based on the 10-year survival data is now presented . PATIENTS AND METHODS A total of 1654 patients treated for gastric cancer between 1986 and 1989 at 19 centers in Germany and Austria were included . The resected specimen were evaluated histopathologically according to a st and ardized protocol . The extent of lymphadenectomy was classified after surgery based on the number of removed lymph nodes on histopathologic assessment ( 25 or fewer removed nodes , D1 or st and ard lymphadenectomy ; > 25 removed nodes , D2 or extended lymphadenectomy ) . Endpoint of the study was death . Follow-up is complete for 97 % of the included patients ( median follow-up of the surviving patients is 8.4 years ) . Prognostic factors were assessed by multivariate analysis . RESULTS A complete macroscopic and microscopic tumor resection ( R0 resection according to the UICC 1997 ) could be achieved in 1182 of the 1654 patients ( 71.5 % ) . The calculated 10-year survival rate in the entire patient population was 26.3 % + /- 4.7 % ; it was 36.1 % + /- 1.6 % after an R0 resection . In the total patient population there was an independent prognostic effect of the ratio between invaded and removed lymph nodes , the residual tumor ( R ) category , the pT category , the presence of postsurgical complications , and the presence of distant metastases . Multivariate analysis in the subgroup of patients who had a UICC R0 resection confirmed the nodal status , the pT category , and the presence of postsurgical complications as the major independent prognostic factors . The extent of lymph node dissection had a significant and independent effect on the 10-year survival rate in patients with stage II tumors . This effect was present in the subgroups with ( pT2N1 ) and without ( pT3N0 ) lymph node metastases on st and ard histopathologic assessment . The beneficial effect of extended lymph node dissection for stage II tumors persisted when patients with insufficient lymph node dissection ( < 15 nodes ) were excluded from the analysis . There was no difference in the postsurgical morbidity and mortality rates between patients with st and ard and extended lymph node dissection . CONCLUSIONS Lymph node ratio and lymph node status are the most important prognostic factors in patients with resected gastric cancer . In experienced centers , extended lymph node dissection does not increase the mortality or morbidity rate of resection for gastric cancer but markedly improves long-term survival in patients with stage II tumors . This effect appears to be independent of the phenomenon of stage migration BACKGROUND A regimen of epirubicin , cisplatin , and infused fluorouracil ( ECF ) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma . We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer . METHODS We r and omly assigned patients with resectable adenocarcinoma of the stomach , esophagogastric junction , or lower esophagus to either perioperative chemotherapy and surgery ( 250 patients ) or surgery alone ( 253 patients ) . Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin ( 50 mg per square meter of body-surface area ) and cisplatin ( 60 mg per square meter ) on day 1 , and a continuous intravenous infusion of fluorouracil ( 200 mg per square meter per day ) for 21 days . The primary end point was overall survival . RESULTS ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer . Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group ( 46 percent and 45 percent , respectively ) , as were the numbers of deaths within 30 days after surgery . The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group . With a median follow-up of four years , 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died . As compared with the surgery group , the perioperative-chemotherapy group had a higher likelihood of overall survival ( hazard ratio for death , 0.75 ; 95 percent confidence interval , 0.60 to 0.93 ; P=0.009 ; five-year survival rate , 36 percent vs. 23 percent ) and of progression-free survival ( hazard ratio for progression , 0.66 ; 95 percent confidence interval , 0.53 to 0.81 ; P<0.001 ) . CONCLUSIONS In patients with operable gastric or lower esophageal adenocarcinomas , a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival . ( Current Controlled Trials number , IS RCT N93793971 [ controlled-trials.com ] . ) PURPOSE The ARTIST ( Adjuvant Chemoradiation Therapy in Stomach Cancer ) trial was the first study to our knowledge to investigate the role of postoperative chemoradiotherapy therapy in patients with curatively resected gastric cancer with D2 lymph node dissection . This trial was design ed to compare postoperative treatment with capecitabine plus cisplatin ( XP ) versus XP plus radiotherapy with capecitabine ( XP/XRT/XP ) . PATIENTS AND METHODS The XP arm received six cycles of XP ( capecitabine 2,000 mg/m2 per day on days 1 to 14 and cisplatin 60 mg/m2 on day 1 , repeated every 3 weeks ) chemotherapy . The XP/XRT/XP arm received two cycles of XP followed by 45-Gy XRT ( capecitabine 1,650 mg/m2 per day for 5 weeks ) and two cycles of XP . RESULTS Of 458 patients , 228 were r and omly assigned to the XP arm and 230 to the XP/XRT/XP arm . Treatment was completed as planned by 75.4 % of patients ( 172 of 228 ) in the XP arm and 81.7 % ( 188 of 230 ) in the XP/XRT/XP arm . Overall , the addition of XRT to XP chemotherapy did not significantly prolong disease-free survival ( DFS ; P = .0862 ) . However , in the subgroup of patients with pathologic lymph node metastasis at the time of surgery ( n = 396 ) , patients r and omly assigned to the XP/XRT/XP arm experienced superior DFS when compared with those who received XP alone ( P = .0365 ) , and the statistical significance was retained at multivariate analysis ( estimated hazard ratio , 0.6865 ; 95 % CI , 0.4735 to 0.9952 ; P = .0471 ) . CONCLUSION The addition of XRT to XP chemotherapy did not significantly reduce recurrence after curative resection and D2 lymph node dissection in gastric cancer . A subsequent trial ( ARTIST-II ) in patients with lymph node-positive gastric cancer is planned |
2,288 | 27,706,912 | Meta- analysis suggests that mindfulness-based interventions may be effective in significantly reducing state anxiety and depression at posttreatment and state anxiety and trait anxiety at follow-up .
Qualitative studies and uncontrolled studies shed light on benefits overlooked in RCTs , including improvements in the well-being of individuals ( e.g. inner state of calmness , awareness and enthusiasm ) and improved performance at work ( better communication with colleagues and patients , higher sensitivity to patients ' experiences , clearer analysis of complex situations and emotional regulation in stressful context s ) .
Mindfulness appeared to improve nurses ' mental health significantly .
It could be used in worksite health promotion programmes .
Only a few studies have explored the impact of mindfulness on nurses ' professional behaviours and their relationships with patients and colleagues . | AIM To review the effects of mindfulness-based interventions on Registered Nurses and nursing students .
BACKGROUND Work-related stress among nurses is estimated to be the biggest occupational health problem after musculoskeletal disorders . | The purpose of this project is to develop and evaluate a psycho-educational program that assists nurses to develop stress management plans . Discussion of nursing-specific risk factors , practice with relaxation techniques , and exploration via art are used as interventions . Quantitative and qualitative measures of stress and burnout are conducted pre- and postcourse using the Maslach Burnout Inventory , Draw-a-Person-in-the-Rain Art Assessment , and wellness plans . Descriptive statistics are used , and preliminary analysis indicates that the course is useful in impacting levels of emotional exhaustion . There are opportunities for evolving the program so that more enduring change in self-care is generated Highly stressed employees are subject to greater health risks , increased cost , and productivity losses than those with normal stress levels . To address this issue in an evidence -based manner , worksite stress management programs must be able to engage individuals as well as capture data on stress , health indices , work productivity , and health care costs . In this r and omized controlled pilot , our primary objective was to evaluate the viability and proof of concept for two mind-body workplace stress reduction programs ( one therapeutic yoga-based and the other mindfulness-based ) , in order to set the stage for larger cost-effectiveness trials . A second objective was to evaluate 2 delivery venues of the mindfulness-based intervention ( online vs. in-person ) . Intention-to-treat principles and 2 ( pre and post ) × 3 ( group ) repeated- measures analysis of covariance procedures examined group differences over time on perceived stress and secondary measures to clarify which variables to include in future studies : sleep quality , mood , pain levels , work productivity , mindfulness , blood pressure , breathing rate , and heart rate variability ( a measure of autonomic balance ) . Two hundred and thirty-nine employee volunteers were r and omized into a therapeutic yoga worksite stress reduction program , 1 of 2 mindfulness-based programs , or a control group that participated only in assessment . Compared with the control group , the mind-body interventions showed significantly greater improvements on perceived stress , sleep quality , and the heart rhythm coherence ratio of heart rate variability . The two delivery venues for the mindfulness program produced basically equivalent results . Both the mindfulness-based and therapeutic yoga programs may provide viable and effective interventions to target high stress levels , sleep quality , and autonomic balance in employees 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 Part III of the study on mindfulness-based stress reduction ( MBSR ) describes qualitative data and discusses the implication s of the findings . Study analysis revealed that nurses found MBSR helpful . Greater relaxation and self-care and improvement in work and family relationships were among reported benefits . Challenges included restlessness , physical pain , and dealing with difficult emotions Mindfulness-based stress reduction ( MBSR ) has produced behavioral , psychological , and physiological benefits , but these programs typically require a substantial time commitment from the participants . This study assessed the effects of a shortened ( low-dose [ ld ] ) work-site MBSR intervention ( MBSR-ld ) on indicators of stress in healthy working adults to determine if results similar to those obtained in traditional MBSR could be demonstrated . Participants were r and omized into MBSR-ld and wait-list control groups . Self-reported perceived stress , sleep quality , and mindfulness were measured at the beginning and end of the 6-week intervention . Salivary cortisol was assessed weekly . Significant reductions in perceived stress ( p = .0025 ) and increases in mindfulness ( p = .0149 ) were obtained for only the MBSR-ld group ( n = 22 ) . Scores on the global measure of sleep improved for the MBSR-ld group ( p = .0018 ) as well as for the control group ( p = .0072 ; n = 20 ) . Implication s and future research are discussed This article is the second in a series reporting on research exploring the effects of Mindfulness-based Stress Reduction on nurses and describes the quantitative data . The third article describes qualitative data . Treatment group participants reduced scores on 2 of 3 subscales of the Maslach Burnout Inventory significantly more than wait-list controls ; within-group comparisons for both groups pretreatment and posttreatment revealed similar findings . Changes were maintained as long as 3-month posttreatment . Implication s of these findings are discussed OBJECTIVE To assess the effect of a meditation training program , Mindfulness-Based Stress Reduction ( MBSR ) , on depressive symptoms , psychological status , and disease activity in patients with rheumatoid arthritis ( RA ) through a r and omized , waitlist-controlled pilot study . METHODS Participants were r and omized to either an MBSR group , where they attended an 8-week course and 4-month maintenance program , or to a waitlist control group , where they attended all assessment visits and received MBSR free of charge after study end . Participants received usual care from their rheumatologists throughout the trial . Self-report question naires were used to evaluate depressive symptoms , psychological distress , well-being , and mindfulness . Evaluation of RA disease activity ( by Disease Activity Score in 28 joints ) included examination by a physician masked to treatment status . Adjusted means and mean changes in outcomes were estimated in mixed model repeated measures analyses . RESULTS Sixty-three participants were r and omized : 31 to MBSR and 32 to control . At 2 months , there were no statistically significant differences between groups in any outcomes . At 6 months , there was significant improvement in psychological distress and well-being ( P = 0.04 and P = 0.03 , respectively ) , and marginally significant improvement in depressive symptoms and mindfulness ( P = 0.08 and P = 0.09 , respectively ) . There was a 35 % reduction in psychological distress among those treated . The intervention had no impact on RA disease activity . CONCLUSION An 8-week MBSR class was not associated with change in depressive symptoms or other outcomes at 2-month followup . Significant improvements in psychological distress and well-being were observed following MBSR plus a 4-month program of continued reinforcement . Mindfulness meditation may complement medical disease management by improving psychological distress and strengthening well-being in patients with RA This study sought to develop a stress management program based on the arousal-attribution stress model and to evaluate the effectiveness of the program in reducing anxiety and depression experienced by nursing students . Forty-two sophomore and 34 senior nursing students in a private , sectarian , liberal arts college were r and omly assigned to experimental and control groups . All subjects were given pre- and posttests consisting of the State form of the State-Trait Anxiety Inventory and the Institute for Personality and Ability Testing Depression Scale . Posttest analysis indicated that the experimental group had significantly lower anxiety and depression than the control group ( p less than .05 ) . These results support the use of the arousal-attribution stress model as a theoretical framework for stress management training This study examined the effectiveness of a stress coping program based on mindfulness meditation on the stress , anxiety , and depression experienced by nursing students in Korea . A nonequivalent , control group , pre-posttest design was used . A convenience sample of 41 nursing students were r and omly assigned to experimental ( n=21 ) and control groups ( n=20 ) . Stress was measured with the PWI-SF ( 5-point ) developed by Chang . Anxiety was measured with Spieberger 's state anxiety inventory . Depression was measured with the Beck depression inventory . The experimental group attended 90-min sessions for eight weeks . No intervention was administered to the control group . Nine participants were excluded from the analysis because they did not complete the study due to personal circumstances , result ing in 16 participants in each group for the final analysis . Results for the two groups showed ( 1 ) a significant difference in stress scores ( F=6.145 , p=0.020 ) , ( 2 ) a significant difference in anxiety scores ( F=6.985 , p=0.013 ) , and ( 3 ) no significant difference in depression scores ( t=1.986 , p=0.056 ) . A stress coping program based on mindfulness meditation was an effective intervention for nursing students to decrease their stress and anxiety , and could be used to manage stress in student nurses . In the future , long-term studies should be pursued to st and ardize and detail the program , with particular emphasis on studies to confirm the effects of the program in patients with diseases , such as cancer Mindfulness describes a state of consciousness in which individuals attend to ongoing events and experiences in a receptive and non-judgmental way . The present research investigated the idea that mindfulness reduces emotional exhaustion and improves job satisfaction . The authors further suggest that these associations are mediated by the emotion regulation strategy of surface acting . Study 1 was a 5-day diary study with 219 employees and revealed that mindfulness negatively related to emotional exhaustion and positively related to job satisfaction at both the within- and the between-person levels . Both relationships were mediated by surface acting at both levels of analysis . Study 2 was an experimental field study , in which participants ( N = 64 ) were r and omly assigned to a self-training mindfulness intervention group or a control group . Results revealed that participants in the mindfulness intervention group experienced significantly less emotional exhaustion and more job satisfaction than participants in the control group . The causal effect of mindfulness self-training on emotional exhaustion was mediated by surface acting . Implication s for using mindfulness and mindfulness training interventions in organizational research and practice are discussed in conclusion This study implemented an innovative new model of delivering a Mindfulness-Based Stress Reduction ( MBSR ) program that replaces six of the eight traditional in-person sessions with group telephonic sessions ( tMBSR ) and measured the program 's impact on the health and well-being of nurses employed within a large health care organization . As part of a nonr and omized pre – post intervention study , 36 nurses completed measures of health , stress , burnout , self-compassion , serenity , and empathy at three points in time . Between baseline ( Time 1 ) and the end of the 8-week tMBSR intervention ( Time 2 ) , participants showed improvement in general health , t(37 ) = 2.8 , p < .01 , decreased stress , t(37 ) = 6.8 , p < .001 , decreased work burnout , t(37 ) = 4.0 , p < .001 , and improvement in several other areas . Improvements were sustained 4 months later ( Time 3 ) , and individuals who continued their MBSR practice after the program demonstrated better outcomes than those that did not . Findings suggest that the tMBSR program can be a low cost , feasible , and scalable intervention that shows positive impact on health and well-being , and could allow MBSR to be delivered to employees who are otherwise unable to access traditional , on-site programs This qualitative study assesses the experience of an intervention that provided spiritually based self-management tools to hospital-based nurses . Drawing on wisdom traditions of the major world religions , the eight point program can be practice d by adherents to any religious faith , or those outside of all traditions . Five of eight program points were perceived as directly useful in improving the nurses ’ workplace interactions and enhancing fulfillment of compassionate caregiving missions . The findings suggest that this program can be an effective intervention among nurses in dealing with the dem and s of the healthcare environment and may be a re source for continuing education curricula Background . Nursing students experiencing debilitating test anxiety may be unable to demonstrate their knowledge and have potential for poor academic performance . Method . A biofeedback‐assisted relaxation training program was created to reduce test anxiety . Anxiety was measured using Spielberger 's Test Anxiety Inventory and monitoring peripheral skin temperature , pulse , and respiration rates during the training . Participants were introduced to diaphragmatic breathing , progressive muscle relaxation , and autogenic training . Results . Statistically significant changes occurred in respiratory rates and skin temperatures during the diaphragmatic breathing session ; respiratory rates and peripheral skin temperatures during progressive muscle relaxation session ; respiratory and pulse rates , and peripheral skin temperatures during the autogenic sessions . No statistically significant difference was noted between the first and second TAI . Subjective test anxiety scores of the students did not decrease by the end of training . Conclusion . Autogenic training session was most effective in showing a statistically significant change in decreased respiratory and pulse rates and increased peripheral skin temperature AIM This paper reports a study to determine the effectiveness of autogenic training in reducing anxiety in nursing students . BACKGROUND Nursing is stressful , and nursing students also have the additional pressures and uncertainties shared with all academic students . Autogenic training is a relaxation technique consisting of six mental exercises and is aim ed at relieving tension , anger and stress . Meta- analysis has found large effect sizes for autogenic trainings intervention comparisons , medium effect sizes against control groups , and no effects when compared with other psychological therapies . A controlled trial with 50 nursing students found that the number of certified days off sick was reduced by autogenic training compared with no treatment , and a second trial with only 18 students reported greater improvement in Trait Anxiety , but not State Anxiety , compared with untreated controls . METHODS A r and omized controlled trial with three parallel arms was completed in 1998 with 93 nursing students aged 19 - 49 years . The setting was a university college in the United Kingdom . The treatment group received eight weekly sessions of autogenic training , the attention control group received eight weekly sessions of laughter therapy , and the time control group received no intervention . The outcome measures were the State-Trait Anxiety Inventory , the Maslach Burnout Inventory , blood pressure and pulse rate completed at baseline , 2 months ( end of treatment ) , and 5 , 8 , and 11 months from r and omization . RESULTS There was a statistically significantly greater reduction of State ( P<0.001 ) and Trait ( P<0.001 ) Anxiety in the autogenic training group than in both other groups immediately after treatment . There were no differences between the groups for the Maslach Burnout Inventory . The autogenic training group also showed statistically significantly greater reduction immediately after treatment in systolic ( P<0.01 ) and diastolic ( P<0.05 ) blood pressure , and pulse rate ( P<0.002 ) , than the other two groups . CONCLUSION . Autogenic training has at least a short-term effect in alleviating stress in nursing students Summary The impact of learning one relaxation technique , RGI , was assessed as it affected six stress-related variables : anxiety , depression , physical complaints , pulse , blood pressure , and perceived level of tension . Inpatient cancer nurses and home care nurses were r and omly assigned to a training group ( n = 12 ) and a waiting list control group ( n = 11 ) . Only depression showed a significant improvement in the experimental group . A number of questions were raised regarding the changes observed , the lack of significance found , and the differences noted between and within groups . The most intriguing observation was that poor copers ( using Weisman 's heirarchy of coping behaviors ) showed the greatest improvement The purpose of this pilot study was to explore whether co-meditation , shared or cross-breathing , could reduce anxiety and enhance relaxation in a nursing school setting . The specific outcomes to be assessed in the quantitative component were blood pressure , pulse , respirations , and anxiety , both state and trait . A qualitative component explored participants ’ experiences with co-meditation following 1 month of practice . Rogers ’s Science of Unitary Human Beings formed the theoretical basis for this study . The study employed a pretest/posttest design with participants as their own controls . Quantitative data were collected from a convenience sample of 26 students , faculty , and staff aged 19 to 51 years , male and female . Fourteen participants returned for the qualitative component . Findings suggest that co-meditation may be useful in reducing anxiety , as measured by vital signs and the anxiety inventory forms . Participants reported feeling calmer and more relaxed , balanced , and centered following 1 month of practice . Findings suggest that co-meditation has potential to help transform a nursing educational environment from one that is potentially anxiety provoking to a calmer , more caring one Nurse managers are under increased stress because of excessive workloads and hospitals ' restructuring which is affecting their work tasks . High levels of stress could affect their mental health . Yet , few stress management training programmes are provided for this population . The purpose of this study was to apply stretch-release relaxation and cognitive relaxation training to enhance the mental health for nurse managers . A total of 65 nurse managers in Hong Kong were r and omly assigned to stretch-release relaxation ( n = 17 ) , cognitive relaxation ( n = 18 ) , and a test control group ( n = 35 ) . Mental health status was assessed using the Chinese version of State-Trait Anxiety Inventory and the Chinese version of the General Health Question naire . Participants were assessed at the pretreatment session , the fourth posttreatment session , and at the 1-month follow-up session . The results revealed both the stretch-release and cognitive relaxation training enhanced mental health in nurse managers in Hong Kong . The application of relaxation training in enhancing mental health status for nurses and health professionals is discussed The purpose of this study was to investigate the effects of a 5-week stress management program for 40 junior baccalaureate nursing students . A quasi-experimental pretest-posttest control group design was used . The stress management group included training sessions using cognitive modification techniques and Stroebel 's Quieting Response ( QR ) augmented with biofeedback techniques for self-relaxation . A significant reduction of state anxiety ( P < .001 ) was reported on the State-Trait Anxiety Inventory ( STAI ) by the experimental groups , while the state anxiety of the control groups remained relatively unchanged . There were no significant changes in trait anxiety scores . Urinary potassium excretion was measured as an index of the adrenal stress response . Findings revealed no statistically significant correlation between potassium excretion and scores on the STAI . These results support the benefits of integrating a stress management program into curricula for nursing students CONTEXT Abnormal cortisol levels are a key pathophysiological indicator of post-traumatic stress disorder ( PTSD ) . Endogenous normalization of cortisol concentration through exercise may be associated with PTSD symptom reduction . OBJECTIVE The aim of the study was to determine whether mindfulness-based stretching and deep breathing exercise ( MBX ) normalizes cortisol levels and reduces PTSD symptom severity among individuals with sub clinical features of PTSD . DESIGN AND SETTING A r and omized controlled trial was conducted at the University of New Mexico Health Sciences Center . PARTICIPANTS Twenty-nine nurses ( 28 female ) aged 45 - 66 years participated in the study . INTERVENTION Sixty-minute MBX sessions were conducted semiweekly for 8 weeks . MAIN OUTCOME MEASURES Serum cortisol was measured , and the PTSD Checklist-Civilian version ( PCL-C ) was performed at baseline and weeks 4 , 8 , and 16 . RESULTS Twenty-nine participants completed the study procedures , 22 ( 79 % ) with PTSD symptoms ( MBX , n = 11 ; control , n = 11 ) , and 7 ( 21 % ) without PTSD ( BASE group ) . Eight-week outcomes for the MBX group were superior to those for the control group ( mean difference for PCL-C scores , -13.6 ; 95 % confidence interval [ CI ] , -25.6 , -1.6 ; P = .01 ; mean difference for serum cortisol , 5.8 ; 95 % CI , 0.83 , 10.8 ; P = .01 ) . No significant differences were identified between groups in any other items . The changes in the MBX group were maintained at the 16-week follow-up ( P = .85 for PCL-C ; P = .21 for cortisol ) . Our data show that improved PTSD scores were associated with normalization of cortisol levels ( P < .05 ) . CONCLUSIONS The results suggest that MBX appears to reduce the prevalence of PTSD-like symptoms in individuals exhibiting sub clinical features of PTSD OBJECTIVE To assess whether a self-directed , computer-guided meditation training program is useful for stress reduction in hospital nurses . DESIGN We prospect ively evaluated participants before and after a month-long meditation program . The meditation program consisted of 15 computer sessions that used biofeedback to reinforce training . Participants were instructed to practice the intervention for 30 minutes per session , four times a week , for four weeks . Visual analogue scales were used to measure stress , anxiety , and quality of life ( assessment s were performed using Linear Analogue Self- Assessment [ LASA ] , State Trait Anxiety Inventory [ STAI ] , and Short-Form 36 [ SF-36 ] question naires ) . Differences in scores from baseline to the study 's end were compared using the paired t test . RESULTS Eleven registered nurses not previously engaged in meditation were enrolled ; eight completed the study . Intent-to-treat analysis showed significant improvement in stress management , as measured by SF-36 vitality subscale ( P = .04 ) , STAI ( P = .03 ) , LASA stress ( P = .01 ) , and LASA anxiety ( P = .01 ) . Nurses were highly satisfied with the meditation program , rating it 8.6 out of 10 . CONCLUSIONS The results of this pilot study suggest the feasibility and efficacy of a biofeedback-assisted , self-directed , meditation training program to help hospital nurses reduce their stress and anxiety . Optimal frequency of use of the program , as well as the duration of effects , should be addressed in future studies |
2,289 | 21,861,870 | Conclusion The " smoker 's paradox " was observed in some studies of AMI patients in the pre-thrombolytic and thrombolytic era , whereas no studies of a contemporary population with acute coronary syndrome have found evidence for such a paradox | Background Smokers have been shown to have lower mortality after acute coronary syndrome than non-smokers .
This has been attributed to the younger age , lower co-morbidity , more aggressive treatment and lower risk profile of the smoker .
Some studies , however , have used multivariate analyses to show a residual survival benefit for smokers ; that is , the " smoker 's paradox " .
The aim of this study was , therefore , to perform a systematic review of the literature and evidence surrounding the existence of the " smoker 's paradox " . | BACKGROUND Treatment with angiotensin-converting-enzyme ( ACE ) inhibitors reduces mortality among survivors of acute myocardial infa rct ion , but whether to use ACE inhibitors in all patients or only in selected patients is uncertain . METHODS We screened 6676 consecutive patients with 7001 myocardial infa rct ions confirmed by enzyme studies . A total of 2606 patients had echocardiographic evidence of left ventricular systolic dysfunction ( ejection fraction , < or = 35 percent ) . On days 3 to 7 after infa rct ion , 1749 patients were r and omly assigned to receive oral tr and olapril ( 876 patients ) or placebo ( 873 patients ) . The duration of follow-up was 24 to 50 months . RESULTS During the study period , 304 patients ( 34.7 percent ) in the tr and olapril group died , as compared with 369 ( 42.3 percent ) in the placebo group ( P = 0.001 ) . The relative risk of death in the tr and olapril group , as compared with the placebo group , was 0.78 ( 95 percent confidence interval , 0.67 to 0.91 ) . Tr and olapril also reduced the risk of death from cardiovascular causes ( relative risk , 0.75 ; 95 percent confidence interval , 0.63 to 0.89 ; P = 0.001 ) and sudden death ( relative risk , 0.76 ; 95 percent confidence interval , 0.59 to 0.98 ; P = 0.03 ) . Progression to severe heart failure was less frequent in the tr and olapril group ( relative risk , 0.71 ; 95 percent confidence interval , 0.56 to 0.89 ; P = 0.003 ) . In contrast , the risk of recurrent myocardial infa rct ion ( fatal or nonfatal ) was not significantly reduced ( relative risk , 0.86 ; 95 percent confidence interval , 0.66 to 1.13 ; P = 0.29 ) . CONCLUSIONS Long-term treatment with tr and olapril in patients with reduced left ventricular function soon after myocardial infa rct ion significantly reduced the risk of overall mortality , mortality from cardiovascular causes , sudden death , and the development of severe heart failure . That mortality was reduced in a r and omized study enrolling 25 percent of consecutive patients screened should encourage the selective use of ACE inhibition after myocardial infa rct ion Background The aim of the present study was to investigate whether a previously shown survival benefit result ing from routine early invasive management of unselected patients with acute non-ST-segment elevation myocardial infa rct ion ( NSTEMI ) may differ according to smoking status and age . Methods Post-hoc analysis of a prospect i ve observational cohort study of consecutive patients admitted for NSTEMI in 2003 ( conservative strategy cohort [ CS ] ; n = 185 ) and 2006 ( invasive strategy cohort [ IS ] ; n = 200 ) . A strategy for transfer to a high-volume invasive center and routine early invasive management was implemented in 2005 . Patients were subdivided into current smokers and non-smokers ( including ex-smokers ) on admission . Results The one-year mortality rate of smokers was reduced from 37 % in the CS to 6 % in the IS ( p < 0.001 ) , and from 30 % to 23 % for non-smokers ( p = 0.18 ) . Non-smokers were considerably older than smokers ( median age 80 vs. 63 years , p < 0.001 ) . The percentage of smokers who underwent revascularization ( angioplasty or coronary artery bypass grafting ) within 7 days increased from 9 % in the CS to 53 % in the IS ( p < 0.001 ) . The corresponding numbers for non-smokers were 5 % and 27 % ( p < 0.001 ) . There was no interaction between strategy and age ( p = 0.25 ) , as opposed to a significant interaction between strategy and smoking status ( p = 0.024 ) . Current smoking was an independent predictor of one-year mortality ( hazard ratio 2.61 , 95 % confidence interval 1.43 - 4.79 , p = 0.002 ) . Conclusions The treatment effect of an early invasive strategy in unselected patients with NSTEMI was more pronounced among smokers than non-smokers . The benefit for smokers was not entirely explained by differences in baseline confounders , such as their younger age OBJECTIVES This study sought to compare the relation between smoking and the 30-day and 6-month outcome after acute myocardial infa rct ion in an Israeli nationwide survey . BACKGROUND Studies before and during the thrombolytic era reported similar or lower early mortality after acute myocardial infa rct ion in smokers than in nonsmokers . This finding is intriguing and may be misleading because numerous epidemiologic studies have clearly shown that smoking is an independent risk factor for atherosclerosis , myocardial infa rct ion and death . METHODS The study cohort comprised 999 consecutive patients with an acute myocardial infa rct ion from a prospect i ve nationwide survey conducted during January and February 1994 in all coronary care units operating in Israel . The prognosis of 367 patients ( 37 % ) who were smokers ( current smokers and those who smoked up to 1 month before admission ) was compared with that of 632 nonsmokers ( past smokers or those who never smoked ) . RESULTS Smokers were on average 10 years younger and were more frequently men and patients with a family history of coronary heart disease and inferior infa rct ion and less frequently patients with a previous infa rct ion or a history of angina , hypertension and diabetes than nonsmokers . Smokers also had a lower incidence of congestive heart failure on admission or during the hospital period . Thrombolytic therapy ( 49 % vs. 40 % , p < 0.01 ) and aspirin ( 89 % vs. 80 % , p < 0.001 ) were administered more frequently in smokers than nonsmokers . The crude 30-day ( 6.0 % vs. 15.7 % ) and cumulative 6-month ( 7.9 % vs. 21.5 % ) mortality rates were significantly lower ( p < 0.0001 for both ) in smokers than nonsmokers , respectively . However , after adjustment for age , baseline characteristics , thrombolytic therapy and invasive coronary procedures , the lower 30-day ( odds ratio [ OR ] 0.75 , 95 % confidence interval [ CI ] 0.43 to 1.29 , p = 0.30 ) and 6-month ( hazard ratio 0.84 , 95 % CI 0.54 to 1.30 , p = 0.42 ) mortality rates in smokers and nonsmokers were not significantly different . The model had a power of 0.80 for OR 0.50 , with alpha 0.1 . CONCLUSIONS In our nationwide survey , the seemingly better prognosis of smokers early after acute myocardial infa rct ion was no longer evident after adjustment for baseline and clinical variables and may be explained by their younger age and a more favorable risk profile . Smokers develop acute myocardial infa rct ion a decade earlier than nonsmokers . Efforts to lower the prevalence of smoking should continue OBJECTIVES Our purpose was to evaluate the relation between smoking and the outcomes of patients receiving thrombolysis for acute myocardial infa rct ion . BACKGROUND A paradoxic beneficial effect has been observed in smokers with a myocardial infa rct ion . We analyzed outcomes and baseline characteristics of 11,975 nonsmokers , 11,117 ex-smokers and 17,507 current smokers in a multinational trial of thrombolysis for acute myocardial infa rct ion . METHODS Patients were r and omized to one of four thrombolytic protocol s. An angiographic sub study in 2,431 patients evaluated reperfusion , reocclusion and ventricular function . Effects of smoking were evaluated by logistic regression analysis after adjustment for age and gender . A mortality model evaluated the simultaneous effect of baseline characteristics on the prognostic importance of smoking . These processes were performed with data from both the main trial and the angiographic sub study ; then angiographic factors ( coronary anatomy , patency and ejection fraction ) were added to the model . RESULTS Smokers were significantly younger by a mean of 11 years ) and had less comorbidity or severe coronary artery disease than nonsmokers . Nonsmokers had significantly higher hospital and 30-day mortality rates ( 9.9 % and 10.3 % , respectively ) than smokers ( 3.7 % vs. 4 % , respectively , both p < 0.001 ) and more in-hospital complications . The unadjusted odds ratio for 30-day mortality in nonsmokers was 3.36 ( 95 % confidence interval [ CI ] 2.08 to 5.41 ) , 1.21 ( 95 % CI 0.71 to 2.08 ) after adjustment for age and gender and 1.08 ( 95 % CI 0.59 to 1.96 ) after adjustment for all clinical baseline characteristics . CONCLUSIONS Smokers receiving thrombolysis for acute myocardial infa rct ion presented 11 years earlier than nonsmokers , which generally accounted for their better outcome . When other differences in clinical and angiographic baseline factors and therapeutic responses were evaluated , no significant difference in mortality was seen between smokers and nonsmokers BACKGROUND Despite advances in pharmacologic therapy and invasive management strategies for patients with non-ST-segment elevation acute coronary syndromes ( NSTE ACS ) , these patients still suffer substantial morbidity and mortality . OBJECTIVE The objective of this study was to analyze independent predictors of 1-year mortality in patients with high-risk NSTE ACS . DESIGN AND PARTICIPANTS A total of 9,978 patients were assigned to receive enoxaparin or unfractionated heparin ( UFH ) in this prospect i ve , r and omized , open-label , international trial . MEASUREMENTS Vital status at 1 year was collected . Univariable and multivariable predictors of 1-year mortality were identified . Three different multivariable regression models were constructed to identify : ( 1 ) predictors of 30-day mortality ; ( 2 ) predictors of 1-year mortality ; ( 3 ) predictors of 1-year mortality in 30-day survivors . The last model is the focus of this paper . RESULTS Overall , 9,922 ( 99.4 % ) of patients had 1-year follow-up . Of the 56 patients ( 37 UFH-assigned and 19 enoxaparin-assigned ) without 1-year data , 11 patients were excluded because of withdrawal of consent , and 45 could not be located . One-year mortality was 7.5 % ( 7.7 % enoxaparin-assigned patients ; 7.3 % UFH-assigned patients ; P = 0.4 ) . In patients surviving 30 days after enrollment , independent predictors of 1-year mortality included factors known at baseline such as increased age , male sex , decreased weight , having ever smoked , decreased creatinine clearance , ST-segment depression , history of diabetes , history of angina , congestive heart failure , coronary artery bypass grafting , increased heart rate , rales , increased hematocrit , lowered hemoglobin , and higher platelet count . Factors predictive of mortality during the hospitalization and 30-day follow-up period were decreased weight at 30 days from baseline , atrial fibrillation , decreased nadir platelet , no use of beta-blockers and statins up to 30 days , and not receiving an intervention ( c-index = 0.82 ) . CONCLUSIONS Easily determined baseline clinical characteristics can be used to predict 1-year mortality with reasonable discriminative power . These models corroborate prior work in a contemporary aggressively managed population . A model to predict 1-year mortality in patients surviving at least 30 days may be quite helpful to healthcare providers in setting expectations and goals with patients after ACS BACKGROUND Smoking is known to be a strong risk factor for premature atherosclerosis , myocardial infa rct ion , and sudden cardiac death . Unexpectedly , in the reperfusion era , investigators have reported that patients who smoke have a more favorable prognosis after thrombolysis compared with non-smokers . Since smoking is associated with a relatively hyper-coagulable state , we hypothesized that the coronary occlusion responsible for infa rct ion may be primarily thrombotic , with improved outcome relating to enhanced patency or the absence of a residual stenosis after thrombolytic therapy . METHODS AND RESULTS To examine this issue , we evaluated 1619 patients treated with TPA , urokinase , or both in six consecutive myocardial infa rct ion trials , of whom 878 ( 54 % ) were currently smoking . Patients underwent 90-minute and predischarge catheterizations , which were quantified blinded to the patients ' smoking status . As expected , baseline fibrinogen ( 2.8 [ 2.5,3.6 ] versus 2.7 [ 2.4,3.5 ] g/dL , P = .003 ) and hematocrit ( 44 % [ 41 % , 47 % ] versus 43 % [ 40 % , 45 % ] , P = .0001 ) levels were greater in smokers . Although there were no differences between smokers and nonsmokers with regard to 90-minute patency ( 73 % versus 74 % ) , smokers were more likely to have TIMI-3 flow ( 41.1 % versus 34.6 % , P = .034 ) , with a larger minimum lumen diameter of the infa rct stenosis both acutely ( 0.82 [ 0.51 , 1.11 ] versus 0.72 [ 0.43 , 1.04 ] mm , P = .0432 ) and at follow-up ( 1.2 [ 0.8 , 1.74 ] versus 1.0 [ 0.7 , 1.5 ] , P = .002 ) . Although smokers tended to have reduced in-hospital mortality compared with nonsmokers in univariate analysis ( 4.0 % versus 8.9 % , P = .0001 ) , after adjustment for baseline differences between smokers and nonsmokers in age ( 54 [ 47 , 62 ] versus 60 [ 54 , 68 ] years , P < .0001 ) , inferior infa rct location ( 60 % versus 53 % , P < .0001 ) , three-vessel disease ( 16 % versus 22 % , P < .001 ) , and baseline ejection fraction ( 53 % [ 44 % , 60 % ] versus 50 % [ 42 % , 58 % ] , P = .0069 ) , smoking history was of no independent prognostic significance . CONCLUSIONS Therefore , smokers have a relatively hypercoagulable state , documented by increased hematocrit and fibrinogen levels . Quantitative coronary angiographic analysis suggests that the mechanism of infa rct ion in smokers is more often thrombosis of a less critical atherosclerotic lesion compared with nonsmokers . Enhanced perfusion status , as well as favorable baseline clinical and angiographic characteristics , may be responsible for the more benign prognosis of current smokers OBJECTIVES The aim of this study was to examine the interaction between cigarette smoking and the clinical efficacy of clopidogrel in ST-segment elevation myocardial infa rct ion ( STEMI ) . BACKGROUND Cigarette smoking induces cytochrome P450 (CYP)1A2 , which converts clopidogrel into its active metabolite , and prior studies suggest greater inhibition of platelet aggregation by clopidogrel in smokers of > or = 10 cigarettes/day . METHODS The effect of clopidogrel compared with placebo on angiographic and clinical outcomes was examined in 3,429 STEMI patients in the CLARITY-TIMI 28 ( Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infa rct ion 28 ) r and omized trial stratified by smoking intensity as follows : not current smokers ( n = 1,732 ) , and smokers of 1 to 9 ( n = 206 ) , 10 to 19 ( n = 354 ) , 20 to 29 ( n = 715 ) , and > or = 30 cigarettes/day ( n = 422 ) . Logistic regression was used to adjust for other baseline characteristics and interaction terms to test for effect modification . RESULTS Although clopidogrel reduced the rate of the primary end point of a closed infa rct -related artery or death/myocardial infa rct ion before angiography in the CLARITY-TIMI 28 trial , the benefit was especially marked among those who smoked > or = 10 cigarettes/day ( adjusted odds ratio [ OR ] : 0.49 , 95 % confidence interval [ CI ] : 0.37 to 0.66 ; p < 0.0001 ) compared with those who did not ( adjusted OR : 0.72 , 95 % CI : 0.57 to 0.91 ; p = 0.006 ; p(interaction ) = 0.04 ) . Similarly , clopidogrel was significantly more effective at reducing the rate of cardiovascular death , myocardial infa rct ion , or urgent revascularization through 30 days among those who smoked > or = 10 cigarettes/day ( adjusted OR : 0.54 , 95 % CI : 0.38 to 0.76 ; p = 0.0004 ) compared with those who did not ( adjusted OR : 0.98 ; 95 % CI : 0.75 to 1.28 ; p = 0.87 ; p(interaction ) = 0.006 ) . CONCLUSIONS Cigarette smoking seems to positively modify the beneficial effect of clopidogrel on angiographic and clinical outcomes . This study demonstrates that common clinical factors that influence the metabolism of clopidogrel might impact its clinical effectiveness CONTEXT Enoxaparin has demonstrated advantages over unfractionated heparin in low- to moderate-risk patients with non-ST-segment elevation acute coronary syndromes ( ACS ) treated with a conservative strategy . OBJECTIVES To compare the outcomes of patients treated with enoxaparin vs unfractionated heparin and to define the role of enoxaparin in patients with non-ST-segment elevation ACS at high risk for ischemic cardiac complications managed with an early invasive approach . DESIGN , SETTING , AND PARTICIPANTS The Superior Yield of the New Strategy of Enoxaparin , Revascularization and Glycoprotein IIb/IIIa Inhibitors ( SYNERGY ) trial was a prospect i ve , r and omized , open-label , multicenter , international trial conducted between August 2001 and December 2003 . A total of 10 027 high-risk patients with non-ST-segment elevation ACS to be treated with an intended early invasive strategy were recruited . INTERVENTIONS Subcutaneous enoxaparin ( n = 4993 ) or intravenous unfractionated heparin ( n = 4985 ) was to be administered immediately after enrollment and continued until the patient required no further anticoagulation , as judged by the treating physician . MAIN OUTCOME MEASURES The primary efficacy outcome was the composite clinical end point of all-cause death or nonfatal myocardial infa rct ion during the first 30 days after r and omization . The primary safety outcome was major bleeding or stroke . RESULTS The primary end point occurred in 14.0 % ( 696/4993 ) of patients assigned to enoxaparin and 14.5 % ( 722/4985 ) of patients assigned to unfractionated heparin ( odds ratio [ OR ] , 0.96 ; 95 % confidence interval [ CI ] , 0.86 - 1.06 ) . No differences in ischemic events during percutaneous coronary intervention ( PCI ) were observed between enoxaparin and unfractionated heparin groups , respectively , including similar rates of abrupt closure ( 31/2321 [ 1.3 % ] vs 40/2364 [ 1.7 % ] ) , threatened abrupt closure ( 25/2321 [ 1.1 % ] vs 24/2363 [ 1.0 % ] ) , unsuccessful PCI ( 81/2281 [ 3.6 % ] vs 79/2328 [ 3.4 % ] ) , or emergency coronary artery bypass graft surgery ( 6/2323 [ 0.3 % ] vs 8/2363 [ 0.3 % ] ) . More bleeding was observed with enoxaparin , with a statistically significant increase in TIMI ( Thrombolysis in Myocardial Infa rct ion ) major bleeding ( 9.1 % vs 7.6 % , P = .008 ) but nonsignificant excess in GUSTO ( Global Utilization of Streptokinase and t-PA for Occluded Arteries ) severe bleeding ( 2.7 % vs 2.2 % , P = .08 ) and transfusions ( 17.0 % vs 16.0 % , P = .16 ) . CONCLUSIONS Enoxaparin was not superior to unfractionated heparin but was noninferior for the treatment of high-risk patients with non-ST-segment elevation ACS . Enoxaparin is a safe and effective alternative to unfractionated heparin and the advantages of convenience should be balanced with the modest excess of major bleeding OBJECTIVES We sought to determine the relationship between cigarette smoking and outcomes after mechanical reperfusion therapy in acute myocardial infa rct ion ( AMI ) . BACKGROUND Prior studies have found that smokers with AMI have lower mortality rates and a more favorable response to fibrinolytic therapy than nonsmokers . The impact of cigarette smoking in patients undergoing primary percutaneous coronary intervention has not been examined . METHODS In the CADILLAC trial , 2082 patients with AMI were r and omized to percutaneous transluminal coronary angioplasty + /- abciximab versus stenting + /- abciximab . Data on smoking status were prospect ively collected and follow-up continued for 1 year . RESULTS At the time of presentation , 638 ( 31 % ) patients had never smoked , 546 ( 26 % ) were former smokers , and 898 ( 45 % ) were currently smoking . In comparison to nonsmokers , current smokers were younger , more often men , and less frequently had diabetes , hypertension , prior AMI , and triple-vessel coronary disease . Procedural success rates were unrelated to smoking status . Mortality was lowest in current smokers , intermediate in former smokers , and highest in nonsmokers at 30 days ( 1.3 % vs 1.7 % vs 3.5 % , respectively , P = .02 ) and 1 year ( 2.9 % vs 3.7 % vs 6.6 % , P = .0008 ) . After multivariate correction for differences in baseline variables , however , current smoking status was no longer protective from late mortality ( hazard ratio 0.96 , 95 % CI 0.52 - 1.76 , P = .89 ) . CONCLUSIONS The " smoker 's paradox " extends to patients undergoing primary PCI for AMI , with increased survival seen in current smokers , an effect entirely explained by differences in baseline risk and not smoking status per se . The deleterious effects of smoking are expressed in the occurrence of AMI nearly a decade earlier than in nonsmokers , with similar age-adjusted risk , m and ating intensive primary and secondary cigarette-cessation efforts The aim of the present study was to investigate whether the implementation of an early invasive strategy for unselected patients with acute myocardial infa rct ion ( AMI ) would be associated with reduced long-term mortality compared to a conservative approach . In this prospect i ve observational cohort study of consecutive patients admitted for AMI in 2003 ( conservative cohort , n = 311 ) and 2006 ( invasive cohort [ IC ] , n = 307 ) , an 11 % absolute and 41 % relative reduction in 1-year mortality was found for patients with AMI in the IC compared to the conservative cohort ( p = 0.001 ) . These findings were consistent after adjustment for age , gender , previous AMI , previous stroke , diabetes , smoking status , previous left ventricular systolic dysfunction , and serum creatinine at admission ( hazard ratio 0.54 , 95 % confidence interval 0.38 to 0.78 ) and Global Registry of Acute Coronary Events risk score ( hazard ratio 0.67 , 95 % confidence interval 0.46 to 0.97 ) . More patients with ST-segment elevation myocardial infa rct ion received primary percutaneous coronary intervention in the IC ( 57 % vs 3 % , p < 0.001 ) , and a sixfold ( 25 % vs 4 % , p < 0.001 ) increase in early percutaneous coronary intervention ( < 72 hours ) for patients with non-ST-segment elevation myocardial infa rct ion was observed . A greater proportion of patients in the IC received clopidogrel , aspirin , and statins during follow-up ; otherwise , the secondary prevention measures were similar in the 2 cohorts . In conclusion , the introduction of a strategy for routine transfer to a high-volume percutaneous coronary intervention center for early invasive therapy was accompanied by a substantial reduction in mortality among unselected patients with AMI . Differences in unmeasured confounders might have accounted for a part of the difference in outcome |
2,290 | 10,488,364 | the benefit of corticosteroids clearly outweighs their potential harmful effects . | A systematic review of the literature has been undertaken with regard to the use of corticosteroids in women with preterm premature rupture of membranes ( PPROM ) . | A double-blind study was design ed to investigate the effects of antenatal glucocorticoids on the incidence of respiratory distress syndrome ( RDS ) in 128 premature human infants . There was a significant reduction ( P<0.05 ) in the incidence of RDS in the betamethasone-treated infants to 8.7 % compared to an incidence of 22.6 % in the saline-treated controls and 25.0 % in infants whose mothers received methylprednisolone . The effectiveness of betamethasone in reducing RDS was limited to premature infants delivered to mothers with intact fetal membranes and with an initial L/S ratio less than 2.0 . The time between administration of the glucocorticoid and delivery did not significantly affect the incidence of RDS in this study . The failure of methylprednisolone to reduce the development of RDS in premature infants suggests its potential use in maternal therapy during pregnancy with minimal effects on fetal maturation A prospect i ve double-blind r and omized clinical trial was carried out to determine whether glucocorticoid treatment reduces the risk of respiratory distress syndrome ( RDS ) in prematurely born infants . There were 127 infants born to 122 mothers who received either steroid ( dexamethasone phosphate ) or placebo . No differences between groups occurred in risk factors for RDS ( eg , prepartum asphyxia , male sex , cesarean section ) . When those who received a full course of dexamethasone therapy were compared with those who received placebo , a significant reduction was found in risk , severity , and deaths due to RDS . An increased incidence of infection in mothers treated with steroid was evident , particularly after premature rupture of membranes . We conclude that steroids are effective in reducing risk of RDS , but safer and more efficacious approaches for the prevention of RDS should be sought One hundred forty-six pregnant women were enrolled in a prospect i ve double-blind study to assess the effectiveness and side-effects of antenatal administration of betamethasone in the prevention of respiratory distress syndrome ( RDS ) in potentially premature infants . On admission to the study , the women were given , at r and om , either 12 mg of betamethasone or placebo . The same dose was repeated 24 hours later and then weekly up to 34 weeks of gestation . Gestational age of the infants ranged from 25 to 34 weeks , and birth weights ranged between 730 and 2,650 gm . Statistically significant differences in favor of the infants in the betamethasone group were found in the incidence of RDS , 20.7 % in the betamethasone group compared with 59.5 % in the control group ( P less than .005 ) ; in the severity of RDS ( P less than .05 ) ; and in the death rate ( P less than .05 ) . A higher incidence of hypoglycemia was found among infants in the betamethasone group ( P less than .05 ) . Prolonged rupture of the membranes played no protective role against RDS , and the incidence of infection was similar in both groups A r and omized study was conducted to investigate the effects of antenatal corticosteroids and ampicillin in the management of preterm pregnancies under 34 weeks complicated by premature rupture of membranes . Patients with documented lecithin/sphingomyelin ( L/S ) ratios of less than 2.0 and a singleton gestation were eligible to participate in the study . One hundred sixty-five patients qualified and were r and omized , using sealed envelopes , to four study groups . All patients were followed expectantly . Group I ( 41 patients ) received neither ampicillin nor corticosteroids . Group II ( 43 patients ) received 24 mg of antenatal betamethasone . Group III ( 37 patients ) received 2 g of intravenous ampicillin every 6 hours , with discontinuation of antibiotic therapy if cultures were negative for pathogenic bacteria . Group IV ( 44 patients ) received both corticosteroids and ampicillin as described for groups II and III , respectively . Compared with patients not receiving corticosteroids , those administered antenatal corticosteroids experienced a reduction in the incidences of respiratory distress syndrome ( 53 versus 26 % ) , bronchopulmonary dysplasia ( 23 versus 9 % ) , severe grade s of intracranial hemorrhage ( 15 versus 3 % ) , and patent ductus arteriosus ( 18 versus 6 % ) , with no difference in the incidence of maternal or neonatal infection . Compared with patients not receiving antenatal antibiotics , the group of patients treated with ampicillin on admission had a lower incidence of clinical chorioamnionitis ( 4 versus 26 % ) and neonatal sepsis ( 5 versus 10 % ) . This reduction in infectious morbidity by antenatal ampicillin was restricted to those patients ( 28.4 % of the study population ) colonized with group B streptococci . This r and omized study suggests that the outcome of preterm pregnancies with premature rupture of membranes and an L/S ratio less than 2.0 can be improved by the concurrent use of corticosteroids and ampicillin A prospect i ve , r and omized study was conducted comparing the use of betamethasone and early delivery , early delivery alone , and expectant management in patients in the 28th to 34th week of pregnancy with premature rupture of the membranes ( PROM ) . Tocolytic drugs were used to delay delivery until 24 hours had elapsed after the first dose of steroid or 24 to 48 hours of latent period had elapsed in the second group . There were ho significant differences in maternal age , gestation at PROM , maximum maternal temperature , birth weights , maternal hospital days , respiratory distress , maternal sepsis , or delivery routes in the three groups . Comparisons with one other similar prospect i ve , r and omized study support the concept that expectant management offers less risk from tocolytic side effects A prospect i ve r and omized study involving patients with premature rupture of the membranes between the twenty-eighth week and the thirty-fourth week of pregnancy was conducted . Patients with chorioamnionitis , advanced labor , and fetal distress , as well as those with mature lecithin/sphingomyelin ratios and /or Gram stains positive for bacteria , were delivered immediately . The remaining patients were r and omized . One group received betamethasone . Tocolytic agents were used in this group when necessary . After 48 hours all patients given corticosteroids ( CS group ) were delivered ) . The second group was managed expectantly ( EM group ) and were delivered only when spontaneous labor or infection occurred . A total of 160 patients were r and omized , 80 in each group . Maternal outcome , including chorioamnionitis and cesarean section rates , was not different ; however , the endometritis rate was significantly higher in the CS group ( p less than 0.05 ) . Neonatal outcome did not differ in mean birth weights , perinatal death rates , neonatal infections , or incidences of respiratory distress . The frequency of prolonged hospital stay ( greater than 4 weeks ) was higher in the neonates in the CS group ( p less than 0.01 ) . The conclusion is that corticosteroids and active management in patients with premature rupture of the membranes and premature gestations do not decrease the incidence of respiratory distress syndrome or perinatal mortality and may aggravate certain infectious complications OBJECTIVE To assess whether administration of dexamethasone in women with preterm premature rupture of membranes ( PPROM ) has an effect on the prevalence of maternal sepsis , neonatal respiratory distress syndrome ( RDS ) , perinatal mortality and neonatal sepsis in a developing country . SETTING Six public hospitals in South Africa that deal mainly with indigent women . METHOD A multicentre , double-blind , placebo-controlled , r and omised trial was performed on women with PPROM and fetuses of 28 - 34 weeks ' gestation or clinical ly estimated fetal weight between 1,000 and 2,000 g if the gestational age was unknown . Women were r and omised to receive either dexamethasone 24 mg intramuscularly or placebo in two divided doses 24 hours apart . All women received amoxycillin and metronidazole and were managed expectantly . Hexoprenaline was administered if contractions occurred within the first 24 hours after admission to the trial . OUTCOME MEASURES The maternal outcome measures were clinical chorio-amnionitis and postpartum sepsis . The outcome measures for infants were perinatal death , RDS , mechanical ventilation , necrotising enterocolitis , and neonatal infection within 72 hours . RESULTS One hundred and two women who delivered 105 babies were r and omised to the dexamethasone group and 102 women who delivered 103 babies , to the placebo group . The groups were well balanced with regard to clinical features . There was a trend towards fewer perinatal deaths in the dexamethasone group : 4 compared with 10 ( P = 0.16 , odds ratio 0.37 , 95 % confidence intervals 0.09 - 1.34 ) . A sub analysis of mothers who delivered more than 24 hours after admission to the study and their infants revealed a significant reduction in perinatal deaths ; 1 death in the dexamethasone group and 7 in the placebo group , P = 0.047 ( Fisher 's exact test ) . No woman in either group developed severe sepsis , and the incidence of sepsis in the women did not differ significantly . Eleven infants in each group developed sepsis . CONCLUSION This is the first r and omised trial in women with PPROM to compare the effects of the use of corticosteroids with placebo , where all women received prophylactic antibiotics concomitantly with the corticosteroids . A trend towards an improved perinatal outcome was demonstrated in the women who received dexamethasone . There was no increased risk of infection in the women or their infants where dexamethasone was administered . Administration of corticosteroids to women with PPROM has more advantages than disadvantages in developing countries The use of hydrocortisone and timed delivery was compared to expectant management of pregnancies complicated by preterm prematurely ruptured membranes in a prospect i ve r and omized trial of 73 patients . The incidence of maternal and neonatal complications was compared . There was no significant difference in the incidence of respiratory distress syndrome . Steroid-treated mothers had an increased incidence of postpartum febrile morbidity . We conclude that treatment of women with preterm prematurely ruptured membranes with hydrocortisone and timed delivery offers no advantage over expectant management |
2,291 | 23,486,894 | A black box combination of interventions was rigorously evaluated and showed moderate impact on patient care .
This finding suggests that multi method and multiphased CPD has potential for the greatest impact . | This study is based on a systematic review of studies using a r and omized controlled trial or quasi-experimental design in order to synthesize existing evidence evaluating the effectiveness of continuing professional development ( CPD ) interventions in dentistry on learning gains , behavior change , or patient outcomes . | Aim The aim of this study was to determine whether an educational intervention delivered by a computer aided learning package improved the sensitivity and specificity of dentists ' restorative treatment decisions Method The study was a r and omised controlled study using a Solomon three-group design . Ninety-five dentists were r and omly allocated to the three study groups . One group of dentists read the radiographs pre and post an educational intervention , a second group read the radiographs once , after the intervention , and a third group read the radiographs twice , but received no intervention . On each occasion the dentists read 24 surfaces on each of 15 radiographs and made 360 decisions on how certain they were about restoring the tooth surface . Comparisons of mean sensitivity , specificity and areas under ROC curves were made within and between the study groups . Kappa values were used to assess changes in the level of agreement between dentists . Results There were no significant changes in sensitivity , specificity or area under ROC curves caused by the intervention . There was no evidence that the level of agreement between the dentists improved after the intervention . Conclusion A computer aided learning package had no effect on dentists ' treatment decision-making behaviour Objective To investigate the effectiveness and cost-effectiveness of different guideline implementation strategies , using the Scottish Intercollegiate Guidelines Network ( SIGN ) Guideline 42 ' Management of unerupted and impacted third molar teeth ' ( published 2000 ) as a model . Design A pragmatic , cluster RCT ( 2 × 2 factorial design ) .Subjects Sixty-three dental practice s across Scotl and . Clinical records of all 16—24-year-old patients over two , four-month periods in 1999 ( pre-intervention ) and 2000 ( post-intervention ) were search ed by a clinical research er blind to the intervention group . Data were also gathered on the costs of the interventions . Interventions Group 1 received a copy of SIGN 42 Guideline and had an opportunity to attend a postgraduate education course ( PGEC ) . In addition to this , group 2 received audit and feedback ( A and F ) . Group 3 received a computer aided learning ( CAL ) package . Group 4 received A and F and CAL.Principal outcome measurement The proportion of patients whose treatment complied with the guideline . Results The weighted t-test for A and F versus no A and F ( P=0.62 ) and CAL versus no CAL ( P=0.76 ) were not statistically significant . Given the effectiveness results ( no difference ) the cost effectiveness calculation became a cost-minimisation calculation . The minimum cost intervention in the trial consisted of providing general dental practitioners ( GDPs ) with guidelines and the option of attending PGEC courses . Routine data which subsequently became available showed a Scotl and -wide fall in extraction s prior to data collection . Conclusion In an environment in which pre-intervention compliance was unexpectedly high , neither CAL nor A and F increased the dentists ' compliance with the SIGN guideline compared with mailing of the guideline and the opportunity to attend a postgraduate course . The cost of the CAL arm of the trial was greater than the A and F arm . Further work is required to underst and dental professionals ' behaviour in response to guideline implementation strategies Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials Objective To assess the effect of educational outreach visits on antibiotic prescribing for acute dental pain in primary care . Study design R and omised controlled trial ( RCT ) . Setting General dental practice s in four health authority areas in Wales . Subjects and methods General dental practitioners were recruited to the study and r and omly allocated to one of the three study groups ( control group , guideline group or intervention group ) . Following the intervention , practitioners completed a st and ardised question naire for each patient that presented with acute dental pain . Interventions The control group received no intervention . The guideline group received educational material by post . The intervention group received educational material by post and an academic detailing visit by a trained pharmacist . The educational material included evidence -based guidelines on prescribing for acute dental pain and patient information leaflets . Main outcome measures The number of antibiotic prescriptions issued to patients presenting with dental pain and the number of ' inappropriate ' antibiotic prescriptions . Antibiotics were considered to be inappropriate if the patient did not have symptoms indicative of spreading infection . Results A total of 1,497 completed question naires were received from 23 , 20 and 27 general dental practitioners in the control , guideline and intervention group respectively . Patients in the intervention group received significantly fewer antibiotic prescriptions than patients in the control group ( OR ( 95 % CI ) 0.63 ( 0.41 , 0.95 ) ) and significantly fewer inappropriate antibiotic prescriptions ( OR ( 95 % CI ) 0.33 ( 0.21 , 0.54 ) ) . However , antibiotic and inappropriate antibiotic prescribing were not significantly different in the guideline group compared to the control group ( OR ( 95 % CI ) 0.83 ( 0.55 , 1.21 ) and OR ( 95 % CI ) 0.82 ( 0.53 , 1.29 ) respectively ) . Conclusions Strategies based upon educational outreach visits may be successfully employed to rationalise antibiotic prescribing by dental practitioners Background Routine oral examination ( ROE ) refers to periodic monitoring of the general and oral health status of patients . In most developed Western countries a decreasing prevalence of oral diseases underpins the need for a more individualised approach in assigning individualised recall intervals for regular attendees instead of systematic fixed intervals . From a quality -of-care perspective , the effectiveness of the widespread prophylactic removal of m and ibular impacted asymptomatic third molars ( MIM ) in adolescents and adults is also question able . Data on the effectiveness of appropriate interventions to tackle such problems , and for promoting continuing professional development in oral health care are rare . Methods / design This study is a cluster r and omised controlled trial with groups of GDPs as the unit of r and omisation . The aim is to determine the effectiveness and efficiency of small group quality improvement on professional decision-making of general dental practitioners ( GDPs ) in daily practice . Six peer groups ( ' IQual-groups ' ) shall be r and omised either to the intervention arm I or arm II . Groups of GDPs allocated to either of these arms act as each other 's control group . An IQual peer group consists of eight to ten GDPs who meet in monthly structured sessions scheduled for discussion on practice -related topics . GDPs in both trial arms receive recently developed evidence -based clinical practice guidelines ( CPG ) on ROE or MIM . The implementation strategy consists of one interactive IQual group meeting of two to three hours . In addition , both groups of GDPs receive feedback on personal and group characteristics , and are invited to make use of web-based patient risk vignettes for further individual training on risk assessment policy . Reminders ( flow charts ) will be sent by mail several weeks after the meeting . The main outcome measure for the ROE intervention arm is the use and appropriateness of individualised risk assessment in assigning recall intervals , and for the MIM-intervention group the use and appropriateness of individualised m and ibular impacted third molar risk management . Both groups act as each other 's control . Pre-intervention data will be collected in study months one through three . Post-intervention data collection will be performed after nine months AIM To test the hypothesis that an increased utilization of nickel-titanium rotary instrumentation ( NTRI ) by general dental practitioners will lead to an increased frequency of good quality root fillings . A second aim was to determine whether the educational format would exert influence on the quality . METHODOLOGY Dentists were assigned at r and om to three intervention groups : a 4-h lecture ( L-group , n = 40 ) ; a 4-h lecture plus a full day h and s-on course ( LH-group , n = 40 ) ; or a control group receiving no instruction ( n = 68 ) . The control group received education later on in the study . Radiographs of two root filled molar teeth per dentist were selected at r and om before the start of the education program and after a 6-month clinical learning period . Using length , seal and shape of root-fillings a 5-level variable was created . RESULTS The rate of good quality root fillings increased after the introduction of NTRI . Calculated over all types of roots the frequency of excellent ( score 1 ) root fillings increased from 31 % to 51 % ( P = 0.006 ) in the L-group and from 27 % to 47 % ( P = 0.016 ) in the LH-group . The frequency of low quality root-fillings ( score 5 ) dropped in the L-group from 22 % to 16 % ( P = 0.29 ) and in the LH-group from 13 % to 9 % ( P = 0.48 ) . No statistically significant difference was seen among the controls . CONCLUSIONS When NTRI technology replaced manual stainless steel techniques the rate of good quality root fillings increased . A significant drop in the rate of low quality root fillings was not found The objective of this study was twofold , namely to evaluate the effectiveness of a dental clinical practice guideline on the management of asymptomatic impacted lower third molars ( i ) on referral rates and ( ii ) on dentists ' change in knowledge . A two-arm cluster r and omized controlled trial , with pre- and post-test assessment s , was conducted . A guideline was implemented by multifaceted interventions ( i.e. feedback , reminders , and an interactive meeting ) . The effect was evaluated after 1 yr by repeating the baseline question naire and by monitoring the number of patients who were referred for removal of their asymptomatic impacted m and ibular third molars . Instruments were question naires for detecting changes in knowledge , patient records , and panoramic radiographs . The knowledge of dentists regarding asymptomatic m and ibular third molar management was found to increase significantly in the intervention group as compared to the control group . There was no statistically significant difference between the groups in guideline -consistent patient referral rates at the post-test assessment . It was concluded that the methodology employed for dissemination and implementation of a clinical practice guideline on asymptomatic m and ibular third molar management improves dentists ' knowledge on this topic and is effective in improving decision-making in simulated cases ; however , no clinical effect was demonstrated BACKGROUND Continuing education is incumbent upon dentists as health professionals , but its promotion may be required , particularly in order to ensure regular professional updating . Continuing professional development may be delivered in a variety of ways , and new strategies and techniques must be evaluated for effectiveness . AIM To evaluate the effectiveness of two interventions utilizing the philosophies and techniques of the discipline of Quality Improvement . METHOD A self- assessment instrument ( a manual ) for quality dental practice was developed using the Delphi technique . A r and omized , controlled trial of the interventions was conducted under field conditions for dental practice in Victoria , Australia . Dentists in Test Groups 1 and 2 completed the self- assessment manual , and received relevant references and their own scores for the manual in comparison with empirical st and ards . Dentists in Test Group 1 also attended a continuing education course on Quality Improvement . Dentists in Control Group 1 completed the manual only and received feedback of their scores . Dentists in Test Groups 1 and 2 , and in Control Group 1 completed the manual again after 1 year as a post-intervention follow-up . Dentists in Control Group 2 completed the manual only at 1 year . RESULTS The intervention involving self- assessment , receipt of scores and references for the manual result ed in modest improvements in total scores for dentists after 1 year , although a response bias was apparent . CONCLUSION An effective method of facilitating change in quality dental practice was identified . Assessment of strategies and techniques for professional development of dentists should include observation of patterns of participation This study evaluated the effects of three modes of education on dentists ' knowledge , attitudes , and use of pit and fissure sealants . A r and omly selected group of dentists was invited to participate in a sealant education initiative . During a 12-month period , a total of 662 dentists either ( 1 ) attended continuing education courses , ( 2 ) received written material s and videotapes by mail , or ( 3 ) received only written material s by mail . A comparison group ( n = 337 ) received no material s until after the education phase and evaluation had been completed . Pre- and postintervention surveys were used to measure changes in knowledge , attitudes , and sealant use . Response rates to the two surveys were 62 percent and 76 percent , respectively . Preintervention values for knowledge scores , an attitude scale , and sealant use were similar among the four groups . At followup , the three education groups had significantly higher knowledge scores than the comparison group . Attitude values for all but one group were not significantly different , and sealant use by all groups was identical . The numbers of respondents not using sealants declined slightly between surveys in the three education groups while rising slightly in the No-Education Group . Because program outcomes were similar to those of another sealant initiative , it can probably be concluded that continuing education will increase dentists ' knowledge about sealants , but have little effect upon their attitudes or their use of the technique . The changes observed in this investigation may be due to the particular capacity for cognitive and affective changes of participants , characteristics of the technology being promoted , and external forces in the professional environment Background Interventions to enhance the implementation of evidence -based practice have a varied success rate . This may be due to a lack of underst and ing of the mechanism by which interventions achieve results . Purpose Use psychological models to further an underst and ing of trial effects by piggy-backing on a r and omised controlled trial testing 2 interventions ( Audit & Feedback and Computer-aided Learning ) in relation to evidence -based third molar management . Method All participants of the parent trial ( 64 General Dental Practitioners across Scotl and ) , regardless of intervention group , were invited to complete a question naire assessing knowledge and predictive measures from Theory of Planned Behaviour and Social Cognitive Theory . The main outcome was evidence -based extracting behaviour derived from patient records . Results Neither intervention significantly influenced behaviour in the parent trial . This study revealed that the interventions did enhance knowledge , but knowledge did not predict extraction behaviour . However , the interventions did not influence variables that did predict extraction behaviour ( attitude , perceived behavioural control , self-efficacy ) . Results suggest both interventions failed because neither influenced possible mediating beliefs for the target behavior . Conclusion Using psychology models eluci date d intervention effects and allowed the identification of factors associated with evidence based practice , providing the basis for improving future intervention design In Western European countries , dentists use st and ardized procedures , rather than individualized risk assessment , for routine oral examinations . The predictive hypothesis was that guideline implementation strategies based on multifaceted interventions would be more effective in patient care than the dissemination of guidelines only . A cluster-r and omized trial was conducted , with groups of general dental practitioners ( GDPs ) as the unit of r and omization . Patients were clustered within practice s and prospect ively enrolled in the trial . Patient data were collected from registration forms . The primary outcome measure was guideline -adherent recall assignment , and a secondary outcome measure was guideline -adherent bitewing frequency . The interventions consisted of online training , guideline dissemination , and educational sessions . For low-risk patients , guideline -adherent recall increased in the intervention group ( + 8 % ) , which differed from the control group ( −6.1 % ) ( p = 0.01 ) . Guideline -adherent bitewings showed mixed results . We conclude that multifaceted intervention had a moderate but relevant effect on the performance of GDPs , which is consistent with other findings in primary care |
2,292 | 19,816,459 | A generalisation on dental prophylaxis before PATF can not be applied to adolescents and adults .
Available evidence ( two other studies ) fails to demonstrate any benefit in the prevention of gingivitis from further dental prophylaxis at interval used for recall examinations .
Dental prophylaxis at intervals of four months or more is not justified for the prevention of gingivitis in the general population | Background The purpose of this systematic review was to assess the efficacy of routine dental prophylaxis applied before professionally applied topical fluoride ( PATF ) or at a regular recall visit in the prevention of caries or gingivitis . | AIM To evaluate , in young adults , the effect of different preventive programmes on oral hygiene and to determine whether the variables investigated are predictors of gingival health . MATERIAL AND METHODS This r and omized , blinded , parallel , controlled clinical study examined the effectiveness of three dental health programmes . Four hundred subjects aged 20 - 27 years , 211 males and 189 females , participated in the study . They were recruited from a Public Dental Service clinic and from a private dental practice in Jönköping , Sweden . The effect of the programmes on plaque and gingivitis was evaluated over a 3-year period . The programmes included activities that were adapted for individuals as well as for groups . The plaque indices ( PLI ) and gingival indices ( GI ) were used to evaluate the programmes . RESULTS All programmes result ed in a decrease in PLI and GI . The greatest decrease was found in the group that was followed-up every 2 months . Professional tooth cleaning was non-significant for the clinical result . Gingival health at baseline , participation in any of the test programmes , and knowledge of the dental diseases caries , gingivitis or periodontitis were significant predictors of good gingival health . CONCLUSIONS The study confirms the efficacy of three different preventive programmes in reducing supragingival plaque and gingival inflammation . Professional tooth cleaning provided no clinical benefit beyond that derived from individual and group-based health education The present report describes the result of a clinical trial in which a group of adults have been maintained on a proper oral hygiene st and ard over a 6-year period . In 1971 - -72 , 375 individuals were recruited to a test group and 180 to a control group . During the 6 years of trial , 65 persons from the test group and 34 controls were lost . The patients were divided into three age groups ; I less than 35 years , II 36 - -50 years , III greater than 50 years . The members of the test and control groups were first subjected to a Baseline examination which included assessment s of oral hygiene , gingivitis , periodontal disease and caries . Following this examination all caries lesions were treated and ill-fitting dental restorations adjusted . Each patient was also given a detailed case presentation and a dental prophylaxis . The control group patients were not involved in any further dental health programs during the subsequent 6-year period . Once a year , however , they were recalled to a public dental health clinic for examination and received symptomatic dental treatment . The test group participants , on the other h and , were given a preventive treatment , repeated once every 2 - 3 months which included ( 1 ) instruction and practice in oral hygiene techniques and ( 2 ) meticulous prophylaxis . The patients were re-examined 3 and 6 years after the baseline examination . At the Follow-up examinations the parameters studied at the Baseline examination were recorded again . The findings demonstrated that a preventive program which stimulates individuals to adopt proper oral hygiene habits may resolve gingivitis and prevent progression of periodontal disease and caries . Traditional dental care , on the other h and , did not prevent the progression of caries and periodontitis in adults 69 adults ranging in age from 20 to 73 ( mean age : 37 ) were r and omly assigned to a control ( C ) and a test ( T ) group . Of these , 61 completed the 3-year longitudinal study . All subjects had varying degrees of gingivitis at the start , but no overt periodontitis . Following a base line examination for P1I , GI , probing depth ( PD ) and recession , a differential darkfield microscopic ( DDFM ) count of subgingival bacterial morphotypes was carried out on a pooled sample originating from one tooth surface in each sextant with the greatest probing depth . Examinations were repeated every 6 months for 3 years . The C group received regular prophylaxes every 6 months . The T subjects received prophylaxes according to a previously described schedule , and on the basis of the DDFM test outcome . Recall intervals at the end of the study for the T group ranged from 1 to 24 months ( mean : 15.7 months ) . Of 30 subjects in the T group at the end of the study , one half had not had their teeth cleaned for periods of 18 to 36 months without any detectable deterioration in their periodontal status by comparison with the other T subjects or the patients in the C group . Both C and T subjects exhibited increased mean P1I and GI scores as compared to base line during the first half of the study . However , mean PD measurements remained unchanged . Increases in PD from base line of 3 mm or more were observed only in approximately 1 out of a 1000 individual tooth surface comparisons , a frequency comparable to that expected to occur by chance alone . This observation indicates that in this population , little if any pocket formation occurred during the study period . GI score increases of 2 units or more occurred in relatively few subjects . 2 of 31 C patients accounted for 42 % of the affected dental units , while 5 out of 30 T subjects accounted for 40.8 % of the affected dental units in that group . These observations suggest that despite the relatively high prevalence and incidence of gingivitis , the subjects were relatively resistant to periodontitis . Neither preventive schedule was effective in eliminating gingivitis . The lack of significant destructive disease in this population prevented any meaningful comparison of the relative effectiveness of the two preventive maintenance regimens in preventing recurrences of periodontitis The beneficial effects of comprehensive dental prophylaxis programs are well recognized . In order to study the factors determining the effectiveness of these programs , 28 periodontal recall patients were subjected to monthly professional mechanical tooth cleanings . Experimental and control teeth were r and omly selected according to a splitmouth cross-over method . The Plaque and Gingival indices were recorded 1 month prior to the study , at the start , and at 4 , 8 , and 12 months . One month prior to the study calculus and bacterial plaque were thoroughly removed from all teeth . During the study period only the experimental teeth were cleaned . Efforts were made not to influence the oral hygiene of the participants by any other means . Following the initial tooth cleaning and during the preexperimental period the Plaque and Gingival indices decreased to a low level on both the experimental and control teeth ( mean P1I = 0.4 , mean GI = 0.3 ) . This high st and ard of oral hygiene and gingival health was maintained throughout the study period , and no differences could be observed between experimental and control teeth . This indicates that factors other than the mechanical professional cleaning were responsible for the maintenance of gingival health . It is suggested that participation in the program in itself may have motivated the patients to improve their oral home care The twice yearly application to children 's teeth of acidulated phosphate fluoride ( APF ) gel in dental trays preceded by a professionally rendered ' dental prophylaxis ' has become the st and ard and most commonly used dental chairside procedure for prevention of dental caries . This study was a r and omized , 3-year , community-based clinical trial of professionally applied APF gel involving the use and non-use of a prior dental prophylaxis and annual and biannual APF applications for children in age groups 6 - 7 ( n = 176 ) and 10 - 11 ( n = 153 ) years initially , who are likely at high risk of future dental caries . The 3-year results of this study show no significant effect on dental caries reduction of either a prior prophylaxis or annual versus biannual APF gel applications . A significant reduction in the frequency of provision of these dental services , limited to high caries risk patients only , is recommended |
2,293 | 24,173,606 | AUTHORS ' CONCLUSIONS Prophylactic oxytocin at any dose decreases both PPH greater than 500 mL and the need for therapeutic uterotonics compared to placebo alone .
If IV delivery is not possible , IM delivery may be used as this route of delivery did show a benefit to prevent PPH greater than 500 mL and there was a trend to decrease the need for therapeutic uterotonics , albeit not statistically significant .
Prophylactic oxytocin was superior to ergot alkaloids in preventing PPH greater than 500 mL ; however , in subgroup analysis this benefit did not persist when only r and omised trials with low risk of method ologic bias were analysed .
Based on this , there is limited high- quality evidence supporting a benefit of prophylactic oxytocin over ergot alkaloids .
Importantly , there is no evidence to suggest that prophylactic oxytocin increases the risk of retained placenta when compared to placebo or ergot alkaloids . | BACKGROUND Active management of the third stage of labour has been shown to reduce the risk of postpartum haemorrhage ( PPH ) greater than 1000 mL. One aspect of the active management protocol is the administration of prophylactic uterotonics , however , the type of uterotonic , dose , and route of administration vary across the globe and may have an impact on maternal outcomes .
OBJECTIVES To determine the effectiveness of prophylactic oxytocin at any dose to prevent PPH and other adverse maternal outcomes related to the third stage of labour . | Oxytocin was administered in a r and omized fashion via either the umbilical or maternal intravenous route . Women who received intraumbilical oxytocin had significantly greater calculated blood loss compared with those who received peripheral administration ( P = .01 ) . This greater blood loss was confirmed by a decrease in hematocrit and hemoglobin concentrations after delivery . There was no difference between the groups in the length of the third stage of labor . The incidence of fetomaternal transfusion was higher in the intraumbilical group ( P = .07 ) . We conclude that intraumbilical oxytocin is no more beneficial than peripheral administration Objective To compare intravenous oxytocin administration ( Partocon ® 10 IU ) with saline solution in the management of postpartum haemorrhage in the third stage of labour OBJECTIVE --To compare the effects on fetal and maternal morbidity of routine active management of third stage of labour and expectant ( physiological ) management , in particular to determine whether active management reduced incidence of postpartum haemorrhage . DESIGN --R and omised trial of active versus physiological management . Women entered trial on admission to labour ward with allocation revealed just before vaginal delivery . Five months into trial high rate of postpartum haemorrhage in physiological group ( 16.5 % v 3.8 % ) prompted modification of protocol to exclude more women and allow those allocated to physiological group who needed some active management to be switched to fully active management . Sample size of 3900 was planned , but even after protocol modification a planned interim analysis after first 1500 deliveries showed continuing high postpartum haemorrhage rate in physiological group and study was stopped . SETTING --Maternity hospital . PARTICIPANTS --Of 4709 women delivered from 1 January 1986 to 31 January 1987 , 1695 were admitted to trial and allocated r and omly to physiological ( 849 ) or active ( 846 ) management . Reasons for exclusion were : refusal , antepartum haemorrhage , cardiac disease , breech presentation , multiple pregnancy , intrauterine death , and , after May 1986 , ritodrine given two hours before delivery , anticoagulant treatment , and any condition needing a particular management of third stage . INTERVENTIONS --All but six women allocated to active management actually received it , having prophylactic oxytocic , cord clamping before placental delivery , and cord traction ; whereas just under half those allocated to physiological management achieved it . A fifth of physiological group received prophylactic oxytocic , two fifths underwent cord traction and just over half clamping of the cord before placental delivery . ENDPOINT -- Reduction in incidence of postpartum haemorrhage from 7.5 % under physiological management to 5.0 % under active management . MEASUREMENTS AND MAIN RESULTS --Incidence of postpartum haemorrhage was 5.9 % in active management group and 17.9 % in physiological group ( odds ratio 3.13 ; 95 % confidence interval 2.3 to 4.2 ) , a contrast reflected in other indices of blood loss . In physiological group third stage was longer ( median 15 min v 5 min ) and more women needed therapeutic oxytocics ( 29.7 % v 6.4 % ) . Apgar scores at one and five minutes and incidence of neonatal respiratory problems were not significantly different between groups . Babies in physiological group weighed mean of 85 g more than those in active group . When women allocated to and receiving active management ( 840 ) were compared with those who actually received physiological management ( 403 ) active management still produced lower rate of postpartum haemorrhage ( odds ratio 2.4;95 % CI1.6 to 3.7 ) . CONCLUSIONS --Policy of active management practised in this trial reduces incidence of postpartum haemorrhage , shortens third stage , and results in reduced neonatal packed cell volume The authors analysed the effect of the i.v . oxytocin induced third stage of labour in a controlled trial concerning 1000 patients . The appliance of such an policy in a unit that already had a fairly active management of delivery was very encouraging . The incidence of post-partum haemorrhage ( greater than 500 ml ) is significantly ( P less than 0.001 ) less than in the control group ; and the same for severe haemorrhage . The third stage is significantly ( P less than 0.001 ) shorter in the oxytocin-injected group than in the control group . Moreover , there is no significant difference between the two groups for retained placenta . The economy of blood transfusion , which is a major concern nowadays , could be the real interest of this active management of the third stage of labour Cynthia Stanton and colleagues conducted a cluster-r and omized controlled trial in rural Ghana to assess whether oxytocin given by injection by community health officers at home births was a feasible and safe option in preventing postpartum hemorrhage . Please see later in the article for the Editors ' Background Hemorrhage is the leading direct cause of maternal death globally . While oxytocin is the drug of choice for postpartum hemorrhage prevention , its use has generally been limited to health facilities . This trial assesses the effectiveness , safety , and feasibility of exp and ing the use of prophylactic intramuscular oxytocin to peripheral health care providers at home births in four predominantly rural districts in central Ghana . Methods This study is design ed as a community-based cluster-r and omized trial in which Community Health Officers are r and omized to provide ( or not provide ) an injection of oxytocin 10 IU via the UnijectTM injection system within one minute of delivery of the baby to women who request their presence at home at the onset of labor . The primary aim is to determine if administration of prophylactic oxytocin via Uniject ™ by this cadre will reduce the risk of postpartum hemorrhage by 50 % relative to deliveries which do not receive the prophylactic intervention . Postpartum hemorrhage is examined under three sequential definitions : 1 ) blood loss ≥500 ml ( BL ) ; 2 ) treatment for bleeding ( TX ) and /or BL ; 3 ) hospital referral for bleeding and /or TX and /or BL . Secondary outcomes address safety and feasibility of the intervention and include adverse maternal and fetal outcomes and logistical concerns regarding assistance at home births and the storage and h and ling of oxytocin , respectively . Discussion Results from this trial will build evidence for the effectiveness of exp and ing the delivery of this established prophylactic intervention to peripheral setting s. Complementary data on safety and logistical issues related to this intervention will assist policymakers in low-income countries in selecting both the best uterotonic and service delivery strategy for postpartum hemorrhage prevention . Results of this trial are expected in mid-2013 . The trial is registered at Clinical Trials.gov : NCT01108289 Background There are two approaches to care during the third stage of labour : Active management includes three components : administration of a prophylactic uterotonic drug , cord clamping and controlled cord traction . For physiological care , intervention occurs only if there is clinical need . Evidence to guide care during the third stage is limited and there is variation in recommendations which may contribute to differences in practice . This paper describes current UK practice during the third stage of labour . Methods A postal survey of 2230 fellows and members of the Royal College of Obstetricians and Gynaecologists ( RCOG ) and 2400 members of the Royal College of Midwives was undertaken . Respondents were asked about care during the third stage of labour , for vaginal and caesarean births and their views on the need for more evidence to guide care in the third stage . The data were analysed in Excel and presented as descriptive statistics . Results 1189 ( 53 % ) fellows and members of the RCOG and 1702 ( 71 % ) midwives responded , of whom 926 ( 78 % ) and 1297 ( 76 % ) respectively had conducted or supervised births in the last year . 93 % ( 863/926 ) of obstetricians and 73 % ( 942/1297 ) of midwives report ' always or usually ' using active management . 66 % ( 611/926 ) of obstetricians and 33 % ( 430/1297 ) of midwives give the uterotonic drug with delivery of the anterior shoulder ; this was intramuscular Syntometrine ® for 79 % ( 728/926 ) and 86 % ( 1118/1293 ) respectively . For term births , 74 % ( 682/926 ) of obstetricians and 41 % ( 526/1297 ) of midwives clamp the cord within 20 seconds , as do 57 % ( 523/926 ) and 55 % ( 707/1297 ) for preterm births . Controlled cord traction was used by 94 % of both obstetricians and midwives . For caesarean births , intravenous oxytocin was the uterotonic used by 90 % ( 837/926 ) of obstetricians ; 79 % ( 726/926 ) clamp the cord within 20 seconds for term births as do 63 % ( 576/926 ) for preterm births . Physiological management was used ' always or usually ' by 2 % ( 21/926 ) of obstetricians and 9 % ( 121/1297 ) of midwives . 81 % ( 747/926 ) of obstetricians and 89 % ( 1151/1297 ) of midwives thought more evidence from r and omised trials was needed ; the most popular question was when is best to clamp the cord . Conclusions Active management of the third stage of labour is widely used by both obstetricians and midwives in the UK . Syntometrine ® is usually used for vaginal births and oxytocin for caesarean births ; when this is given and when the cord is clamped varies OBJECTIVE Comparison of 3 regimens for third-stage management after second-trimester intravaginal misoprostol termination . STUDY DESIGN Prospect i ve r and omized trial . Three third-stage management strategies were compared : 10 units of intramuscular oxytocin ( group 1 ) , 600 microg oral misoprostol ( group 2 ) , or no additional medication ( group 3 ) after fetal expulsion . Primary study outcome was the incidence of placental retention . RESULTS Two hundred fifty-one women were r and omly assigned to the groups . There was a significant difference in placental retention rates : group 1 , 8 of 83 ( 10 % ) vs group 2 , 24 of 83 ( 29 % ) vs group 3 , 26 of 85 ( 31 % ) ; P = .002 . Blood loss was significantly lower in group 1 , 100 mL ( interquartile ranges , 50 - 200 ) vs group 2 , 200 mL ( interquartile ranges , 100 - 370 ) vs group 3 , 200 mL ( interquartile ranges , 100 - 375 ) ; P < .001 . Requirement for blood transfusion : group 1 , 1 of 83 ( 1 % ) vs group 2 , 1 of 83 ( 1 % ) vs group 3 , 5 of 85 ( 6 % ) ; P = .103 . CONCLUSION Intramuscular oxytocin administered after fetal delivery after second-trimester medical termination significantly increases placental expulsion rates and decreases short-term postpartum blood loss Background . The single most common direct obstetric disorder accounting for 25 % of all maternal deaths globally is severe hemorrhage , generally occurring postpartum . Nearly all these deaths occur in the developing world . The role of oxytocic drugs in the management of the third stage of labor as a strategy to reduce maternal mortality has been emphasized . However , the adverse effects of these oxytocic agents , in particular ergometrine , have not been properly evaluated in our environment . Objectives . To evaluate the effect of ergometrine and oxytocin on the cardiovascular system when used for active management of the third stage of labor . Study design . A double-blind , r and omized controlled study was carried out at the Federal Medical Centre , Makurdi over 24 months . Five hundred and ten patients were r and omized to treatment with either 0.5 mg of intramuscular ergometrine or 10 IU of intravenous oxytocin , respectively , as single injections . Their effects on the cardiovascular system were observed using blood pressure as a marker . Results . Ergometrine unlike oxytocin was observed to cause a significant rise in blood pressure , and this effect was most marked in the first 24 hours of the puerperium . Conclusions . These results suggest that ergometrine may be safe in normotensive parturients but hazardous in hypertensive parturients in whom oxytocin would be a safer option The incidences of postpartum haemorrhage and retained placenta have decreased with the use of synthetic oxytocin and controlled cord traction . Whether such treatment is valuable is open to question because of the lack of clinical and physiological studies . The physiological effects of synthetic oxytocin on plasma concentrations of oxytocin and events during delivery were assessed . Plasma oxytocin concentration was determined in serial sample s during the late second stage and throughout the third stage of labour in 25 women . Ten women received combined ergotamine and synthetic oxytocin intramuscularly and 15 were not treated . The geometric mean plasma oxytocin concentration significantly increased in the women given oxytocin when measured before and after delivery of the fetal anterior shoulder ( 3.1 ( SD 2.0 ) pmol/l before and 15.9 ( 2.7 ) pmol/l after ) . Six of the women who did not receive treatment showed a significant increase in geometric mean plasma oxytocin concentration before and after delivery of the fetal shoulder ( 3.2 ( 2.0 ) pmol/l before and 6.4 ( 2.0 ) pmol/l after ) and nine did not show an increase ( geometric mean 2.4 ( 3.1 ) pmol/l before and 2.2 ( 2.2 ) pmol/l after ) . Of these nine women , two had an abnormal third stage of delivery ; one woman had a postpartum haemorrhage and one required manual removal of the placenta . As it is impossible to predict which women will show a rise in the plasma concentration of endogenous oxytocin , intramuscular oxytocin should be given routinely Objective To compare the effect of intramuscular Syntometrine and Syntocinon in the management of the third stage of labour OBJECTIVES Our purpose was to compare the controlled cord traction technique with the minimal intervention technique for delivery of the placenta . The primary outcome was the incidence of postpartum hemorrhage . Secondary outcomes included duration of third stage of labor , frequency of retained placenta , hemorrhagic shock , the need for blood transfusion , and the need for uterotonic agents to control postpartum hemorrhage . STUDY DESIGN A total of 1648 women who were delivered vaginally were r and omly allocated during labor to the controlled cord traction group ( n = 827 ) or the minimal intervention group ( n = 821 ) . In the controlled cord traction group women received oxytocin , 10 units intramuscularly , with delivery of the baby 's anterior shoulder , after which the placenta was delivered actively by controlled cord traction ( Br and t- And rews method ) . In the minimal intervention group the placenta was delivered by maternal pushing . Continuous intravenous oxytocin was given after delivery of the placenta . Odds ratios with 95 % confidence intervals were calculated for each variable . RESULTS The overall incidence of postpartum hemorrhage was significantly lower in the controlled cord traction group ( 5.8 % vs 11 % ; odds ratio 0.50 , 95 % confidence interval 0.34 to 0.73 ) . The incidence of retained placenta ( > or = 30 minutes ) was 1.6 % in the controlled cord traction group and 4.5 % in the minimal intervention group ( odds ratio 0.31 , 95 % confidence interval 0.15 to 0.63 ) . Significantly more patients in the minimal intervention group required additional uterotonic agents to control hemorrhage ( 5.1 % vs 2.3 % ; odds ratio 0.44 , 95 % confidence interval 0.24 to 0.78 ) . CONCLUSION The controlled cord traction technique for delivery of the placenta results in a significantly lower incidence of postpartum hemorrhage and retained placenta , as well as less need for uterotonic agents , compared with the minimal intervention technique OBJECTIVE To compare the effect of prophylactic use of oxytocin and ergometrine in management of the third stage of labor . METHODS A prospect i ve r and omized study of 600 women assigned to receive either oxytocin or ergometrine in the third stage of labor . Outcome measures were the predelivery and 48-hour postdelivery hematocrit , duration of the third stage , specific side effects , and incidence of postpartum hemorrhage . Statistical analyses were done using the t test for continuous variables and chi2 test for categorical variables . The level of significance was set at P<0.05 . RESULTS There were no significant differences between the 2 groups in maternal age , gestational age , duration of third stage , birth weights , risk for retained placenta , manual removal of placenta , or need for additional oxytocics . Patients in the ergometrine group were at significant risk for nausea , vomiting , headaches , and elevated blood pressure ( P=0.0001 ) . CONCLUSION Oxytocin is as effective as ergometrine at reducing the incidence of postpartum hemorrhage , but without the undesirable side effects of nausea , vomiting , and elevated blood pressure associated with ergometrine Postpartum hemorrhage ( PPH ) is the most common serious maternal complication of childbirth and the prophylactic use of uterotonic drugs is generally recommended to prevent this complication . Between February and March 2005 a prospect i ve r and omized clinical trial was conducted at the Gynecologic and Obstetric Department of F. Hached Hospital Sousse Tunisia to determine whether the use of oxytocin in the third stage of labor significantly reduced the postpartum blood loss . All women with singleton pregnancies at term who were expected to be delivered vaginally were included . Patients with placenta praevia antepartum hemorrhage noncephalic presentation intrauterine death parity greater than five uterine fibroids anticoagulation therapy and a history of PPH or cesarean delivery were excluded . The women were r and omly allocated to an active management or an expectant management group . In the active management group the women received an intravenous flash injection of 5 I of oxytocin at the time of delivery of the anterior shoulder . The third stage of labor was managed in the same way for all women : immediate clamping and cutting of the cord and delivery of the placenta by controlled cord traction with gentle fundal pressure when signs of placental separation appeared . Manual removal of placenta was used if hemorrhaging occurred and /or if the placenta was not delivered within 30 min of birth . ( excerpt OBJECTIVE To determine the effectiveness of sustained uterine massage started before delivery of the placenta in reducing postpartum hemorrhage . METHODS A r and omized controlled trial conducted in Egypt and South Africa between September 2006 and February 2009 . A total of 1964 pregnant women were r and omly allocated to 1 of 3 treatment groups : intramuscular oxytocin , sustained uterine massage , or both treatments . Blood loss within 30 minutes of delivery was recorded . RESULTS The incidence of blood loss of 300 mL or more within 30 minutes of delivery was significantly higher in the massage group than in the massage plus oxytocin ( RR 1.88 ; 95 % CI , 1.29 - 2.74 in Assiut , and RR 1.3 ; 95 % CI , 1.00 - 1.68 in SA ) and the oxytocin only group ( RR 1.7 ; 95 % CI , 1.11 - 2.61 in Assiut , and RR 2.24 ; 95 % CI , 1.54 - 3.27 in SA ) . In both centers , use of additional uterotonics was significantly higher in the uterine massage group compared with the other 2 groups . CONCLUSION Uterine massage was less effective than oxytocin for reducing blood loss after delivery . When oxytocin was used , there was no additional benefit from uterine massage . The effectiveness of uterine massage in the absence of oxytocin was not studied . ACTRN : 12609000372280 OBJECTIVE To determine the most efficient route and timing of oxytocin administration for active management of the third stage of labor . METHODS A prospect i ve r and omized study was done at one center in Ankara , Turkey , between January and October 2010 . Women with a singleton pregnancy ( > 37 weeks ) who had a live vaginal birth were r and omly allocated to four groups : iv-A ( intravenous oxytocin after delivery of the fetus ) , iv-B ( when anterior shoulder seen ) , im-A ( intramuscular oxytocin after delivery ) , and im-B ( when anterior shoulder seen ) . Postpartum blood loss within the first hour , hemoglobin , hematocrit , and duration of the third stage were compared . RESULTS A total of 600 eligible women were recruited ; 150 were assigned to each group . Postpartum blood loss , prepartum and postpartum hemoglobin and hematocrit , and need for additional uterotonics were similar among groups ( P>0.05 ) . The duration of the third stage of labor and changes in hemoglobin and hematocrit were significantly reduced in group iv-B ( P<0.05 ) . Among women not exposed to oxytocin before delivery , postpartum blood loss was significantly lower in group iv-B ( P=0.019 ) . Labor augmentation was related to significantly increased postpartum blood loss in all groups except iv-A. CONCLUSION Although postpartum blood loss was similar in all groups , early intravenous administration seemed to have beneficial effects . Clinical Trials.gov : NCT01954186 OBJECTIVE To determine the effect of nipple stimulation on uterine activity during the third stage of labor . METHODS R and omized controlled study comparing ; ( i ) 15 min of nipple stimulation ( n = 6 ) , ( ii ) routine syntometrine injection ( n = 3 ) , ( iii ) no action/control ( N = 5 ) . Uterine activity was continuously measured using the placenta as an in-situ hydrostatic bag connected to a pressure transducer . RESULTS Compared to controls uterine pressure was higher during nipple stimulation ( 103 mmHg vs. 70.8 mmHg , P = 0.04 ) . The duration of the third stage and blood loss tended to be reduced with nipple stimulation compared to controls ( 20.3 vs. 12.3 min ) and ( 257 vs. 166 ml ) respectively but was not significant . Similar differences were observed between syntometrine and control groups . CONCLUSIONS For women in developing countries where parenteral oxytocics are not available , nipple stimulation might reduce the incidence of postpartum hemorrhage . A larger trial now seems warranted OBJECTIVE The objective of the study was to compare visually estimated blood loss ( vEBL ) with calculated estimated blood loss ( cEBL ) according to mode of delivery and degree of perineal laceration . STUDY DESIGN Pre- and postdelivery hematocrit ( HCT ) and other variables including vEBL were prospect ively recorded into an obstetrical data base between January and September 2005 . The cEBL was derived by multiplying the calculated pregnancy blood volume ( 0.75 x { [ maternal height ( inches ) x 50 ] + [ maternal weight in pounds x 25 ] } ) by percent of blood volume lost ( { predelivery HCT - postdelivery HCT}/predelivery HCT ) . cEBL and vEBL were compared according to mode of delivery and degree of perineal laceration . RESULTS There were 677 subjects with complete data . vEBL was statistically different from cEBL between each degree of laceration and between all modes of delivery , demonstrating an underestimation of vEBL with increasing cEBL . CONCLUSION Improved methods for calculating blood loss include the use of a modified version of the formula used for pregnancy blood volume calculation OBJECTIVE We sought to identify risk factors for uterine atony or hemorrhage . STUDY DESIGN We conducted a secondary analysis of a 3-arm double-blind r and omized trial of different dose regimens of oxytocin to prevent uterine atony after vaginal delivery . The primary outcome was uterine atony or hemorrhage requiring treatment . In all , 21 potential risk factors were evaluated . Logistic regression was used to identify independent risk factors using 2 complementary predefined model selection strategies . RESULTS Among 1798 women r and omized to 10 , 40 , or 80 U of prophylactic oxytocin after vaginal delivery , treated uterine atony occurred in 7 % . Hispanic ( odds ratio [ OR ] , 2.1 ; 95 % confidence interval [ CI ] , 1.3 - 3.4 ) , non-Hispanic white ( OR , 1.6 ; 95 % CI , 1.0 - 2.5 ) , preeclampsia ( OR , 3.2 ; 95 % CI , 2.0 - 4.9 ) , and chorioamnionitis ( OR , 2.8 ; 95 % CI , 1.6 - 5.0 ) were consistent independent risk factors . Other risk factors based on the specified selection strategies were obesity , induction/augmentation of labor , twins , hydramnios , anemia , and arrest of descent . Amnioinfusion appeared to be protective against uterine atony ( OR , 0.53 ; 95 % CI , 0.29 - 0.98 ) . CONCLUSION Independent risk factors for uterine atony requiring treatment include Hispanic and non-Hispanic white ethnicity , preeclampsia , and chorioamnionitis OBJECTIVE To compare rectally administered misoprostol to intravenously administered oxytocin for the management of third-stage labor . STUDY DESIGN Subjects were r and omized to receive two , 200-microg misoprostol tablets rectally ( study medication ) plus 2 mL saline in Ringer 's lactate intravenously or two lactose tablets rectally plus 20 units oxytocin in Ringer 's lactate intravenously ( control medication ) . Blood loss was determined by estimation , measurement , and change in hematocrit values from admission to postpartum day 1 . Subjects were excluded if cesarean delivery was required . RESULTS A total of 325 women underwent analysis . By estimation , 21 % of subjects and 15 % of controls had postpartum hemorrhage ( P = .17 ) . By using measured blood loss , we determined that 70 of 154 ( 46 % ) study subjects and 61 of 161 ( 38 % ) control subjects had postpartum hemorrhage ( P = .17 ) . For 36 ( 23 % ) misoprostol subjects and 18 ( 11 % ) oxytocin subjects at least one additional agent was required to control bleeding ( P = .004 ) . CONCLUSION Rectal misoprostol ( 400 microg ) was no more effective than intravenous oxytocin in preventing postpartum hemorrhage OBJECTIVES To compare the efficacy of a single 100 micro g intramuscular ( IM ) carbetocin injection , a long-acting oxytocin agonist , to a 2-hour 10 IU oxytocin intravenous ( IV ) infusion , in reducing the incidence and severity of postpartum hemorrhage ( PPH ) in women at risk for this condition . METHODS A r and omized , double-blind , placebo-controlled study was conducted at 2 hospital centres , including 160 women with at least 1 risk factor for PPH . Eighty-three women received 100 microg carbetocin IM and an IV placebo immediately after placental delivery , while 77 women received placebo IM and oxytocin IV infusion . Complete blood count was collected at entry and 24 hours postpartum . All outcome measures , including the need for additional uterotonic agents or uterine massage , blood loss , and drop in hemoglobin and hematocrit , were analyzed using chi-square , Fisher exact , and Student t tests . RESULTS Population profile and risk factors for PPH were similar for each group . No significant difference was observed in the number of women requiring additional uterotonic medication ( 12 in each group ) . However , in the carbetocin group , 36 of the 83 women ( 43.4 % ) required at least 1 uterine massage compared to 48 of the 77 women ( 62.3 % ) in the oxytocin group ( P < .02 ) . Overall , uterotonic intervention was clinical ly indicated in 37 of the women ( 44.6 % ) receiving carbetocin compared to 49 of the women ( 63.6 % ) given an IV oxytocin infusion ( P < .02 ) . There were no differences in laboratory PPH indicators between the 2 groups Purpose One of the major problems in international literature is how to measure postpartum blood loss with accuracy . We aim ed in this research to assess the accuracy of visual estimation of postpartum blood loss ( by each of two main health-care providers ) compared with the gravimetric calculation method . Methods We carried out a prospect i ve cohort study at King Abdulaziz Medical City , Riyadh , Saudi Arabia between 1 November 2009 and 31 December 2009 . All women who were admitted to labor and delivery suite and delivered vaginally were included in the study . Postpartum blood loss was visually estimated by the attending physician and obstetrics nurse and then objective ly calculated by a gravimetric machine . Comparison between the three methods of blood loss calculation was carried out . Results A total of 150 patients were included in this study . There was a significant difference between the gravimetric calculated blood loss and both health-care providers ’ estimation with a tendency to underestimate the loss by about 30 % . The background and seniority of the assessing health-care provider did not affect the accuracy of the estimation . The corrected incidence of postpartum hemorrhage in Saudi Arabia was found to be 1.47 % . Conclusion Health-care providers tend to underestimate the volume of postpartum blood loss by about 30 % . Training and continuous auditing of the diagnosis of postpartum hemorrhage is needed to avoid missing cases and thus preventing associated morbidity and mortality Objective : The objective of this study was to compare the administration of oxytocin at the beginning and end of the third stage of labor for the prevention of postpartum hemorrhage . Methods : Patients with documented singleton pregnancies were r and omly assigned to two groups . The first received 10 units of oxytocin intramuscularly at delivery of the anterior shoulder of the fetus and an identical appearing placebo injection following delivery of the placenta . The second received the opposite medication sequence . The study was double blinded . Blood loss was measured by weighing all fluids collected , visual estimation , and serial blood counts . Results : 27 women received oxytocin at the delivery of the fetal shoulder and 24 after the placenta . Oxytocin given after placenta delivery result ed in lower blood loss ( 345 vs. 400 ml , p = 0.28 ) , lower collection bag weight ( 763 vs. 833 g , p = 0.55 ) , lower change in HgB ( –1.26 vs. –1.32 g , p = 0.86 ) , lower ΔHCT ( –3.43 vs. –3.64 % , p = 0.85 ) , and a shorter third stage of labor duration ( 8.6 vs. 9.2 min , p = 0.75 ) . The incidence of postpartum hemorrhage , defined as estimated blood loss > 500 ml ( 0 vs. 14.8 % ) was significantly lowered with oxytocin following placental delivery ( p = 0.049 ) . Conclusions : In our study , postpartum hemorrhage was less frequent when oxytocin administration was delayed until after placenta delivery Blood loss and the incidence of emetic sequelae were assessed in 148 patients undergoing midcavity forceps delivery under continuous lumbar extradural analgesia . Five units of oxytocin i.v . was found to be as effective as ergometrine 0.5 mg i.v . in reducing blood loss at delivery . Nausea , retching or vomiting occurred in 35 ( 46 % ) of the mothers who received ergometrine and in none of those who received i.v . oxytocin . The cardiovascular side-effects of ergometrine and oxytocin are review ed and compared with special reference to patients with hypertension and heart disease . It is suggested that 5 units of oxytocin i.v . should be preferred in these high-risk patients . Because of the absence of an emetic action , i.v . oxytocin is preferable to i.v . ergometrine for patients receiving extradural analgesia AIM To compare the efficacy and safety of intramuscular oxytocin with intramuscular ergometrine in the management of postpartum hemorrhage during the third stage of labor . METHODS Women who had been pregnant for more than 35 weeks and delivered cephalic singletons vaginally without predelivery administration of oxytocics were included . The cases considered to be at high risk were excluded , such as those who had uterine fibroids , a previous cesarean section , previous postpartum hemorrhage , or severe anemia . Five units of oxytocin or 0.2 mg of methylergometrine were administered intramuscularly immediately after delivery of the baby . RESULTS Compared with intramuscular ergometrine , the use of intramuscular oxytocin was associated with a significant reduction in mean total postpartum blood loss ( 288.16 g vs 354.42 g , P = 0.004 ) , frequency of postpartum hemorrhage ( > or=500 mL : 10.9 % vs 20.32 % , relative risk [ RR ] = 0.54 , 95 % confidence interval [ CI ] = 0.32 - 0.91 ) , and need for therapeutic oxytocics ( 5.13 % vs 12.3 % , RR = 0.42 , 95 % CI = 0.19 - 0.91 ) . There were no differences between the groups in terms of the mean duration of the third stage , the mean level of hemoglobin on the second postpartum day , and the frequency of postpartum hemorrhage ( > or = 1000 mL ) , or manual removal of placenta . Few side-effects were found , with no significant differences between the groups . CONCLUSIONS The routine use of intramuscular oxytocin is more effective than the use of intramuscular ergometrine for prevention of postpartum hemorrhage in the third stage of labor OBJECTIVE To determine if the timing of the administration of prophylactic oxytocin influences the incidence of postpartum hemorrhage caused by uterine atony , retained placenta , and third-stage duration . STUDY DESIGN Parturients who presented for vaginal delivery were r and omized in a double-blinded fashion to receive oxytocin , 20 units in a 500-mL crystalloid intravenous bolus , beginning upon delivery of either the fetal anterior shoulder or placenta . For all patients , the third stage of labor was managed with controlled cord traction until placental expulsion , followed by at least 15 seconds of fundal massage . Patients were excluded if they had a previous cesarean section , multiple gestation , antepartum hemorrhage , or bleeding disorder . RESULTS A total of 1486 patients were enrolled : 745 in the before-placenta group and 741 in the after-placenta group . The groups were similar with respect to gestational age , fetal weight , labor duration , maternal age , parity , and ethnicity . The incidence of postpartum hemorrhage did not differ significantly between the two groups ( 5.4 % vs 5.8 % ; crude OR , 0.92 ; 95 % CI , 0.59 to 1.43 ) . There were no significant differences between the two groups with respect to incidence of retained placenta ( 2.4 % vs 1.6 % ; OR , 1.49 ; 95 % CI , 0.72 to 3.08 ) , or third-stage duration ( 7.7 minutes vs 8.1 minutes ; P = .23 ) . CONCLUSIONS The administration of prophylactic oxytocin before placental delivery does not reduce the incidence of postpartum hemorrhage or third-stage duration , when compared with giving oxytocin after placental delivery . Early administration , however , does not increase the incidence of retained placenta OBJECTIVE : Higher-dose oxytocin is more effective than lower-dose regimens to prevent postpartum hemorrhage after cesarean delivery . We compared two higher-dose regimens ( 80 units and 40 units ) to our routine regimen ( 10 units ) among women who delivered vaginally . METHODS : In a double-masked r and omized trial , oxytocin ( 80 units , 40 units , or 10 units ) was administered in 500 mL over 1 hour after placental delivery . The primary outcome was a composite of any treatment of uterine atony or hemorrhage . Prespecified secondary outcomes included outcomes in the primary composite and a decline of 6 % or more in hematocrit . A sample size of 600 per group ( N=1,800 ) was planned to compare each of the 80-unit and 40-unit groups to the 10-unit group . At planned interim review ( n=1,201 ) , enrollment in the 40-unit group was stopped for futility and enrollment continued in the other groups . RESULTS : Of 2,869 women , 1,798 were r and omized as follows : 658 to 80 units ; 481 to 40 units ; and 659 to 10 units . Most characteristics were similar across groups . The risk of the primary outcome in the 80-unit group ( 6 % ; relative risk [ RR ] 0.93 , 95 % confidence interval [ CI ] 0.62–1.40 ) or the 40-unit group ( 6 % ; RR 0.94 , 95 % CI 0.61–1.47 ) was not different compared with the 10-unit group ( 7 % ) . Treatment with additional oxytocin after the first hour was less frequent with 80 units compared with 10 units ( RR 0.41 , 95 % CI 0.19–0.88 ) , as was a 6 % or more decline in hematocrit ( RR 0.83 , 95 % CI 0.69–0.99 ) ; both outcomes declined with increasing oxytocin dose . Outcomes were similar between the 40-unit and 10-unit groups . CONCLUSION : Compared with 10 units , 80 units or 40 units of prophylactic oxytocin did not reduce overall postpartum hemorrhage treatment when administered in 500 mL over 1 hour for vaginal delivery . Eighty units decreased the need for additional oxytocin and the risk of a decline in hematocrit of 6 % or more . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00790062 . LEVEL OF EVIDENCE : OBJECTIVES A double blind r and omized controlled trial was performed at the tertiary hospital in Harare , Zimbabwe to compare oral misoprostol with intramuscular oxytocin in the management of third stage of labor . METHODS A total of 499 women were r and omized to receive either 400 microg misoprostol orally or 10 IU oxytocin intramuscularly . The incidences of postpartum hemorrhage and side effects were examined . RESULTS The demographic and labor characteristics were comparable . Postpartum hemorrhage occurred in 15.2 % of women given misoprostol and in 13.3 % of those given oxytocin ( P=0.534 ) . Measured blood loss of more than 1000 ml occurred in 3.7 % of the misoprostol group compared with 2 % in the oxytocin group ( P=0.237 ) . There was no significant difference in the need for additional oxytocic drugs or blood transfusion in women given misoprostol ( P values 0.137 and 0.600 , respectively ) . Significant side effects of misoprostol were shivering [ RR=1.32 ( 95 % CI 1.11 - 1.58 ) ; P=0.002 ) and a rise in temperature [ RR=2.02 ( 95 % CI 1.75 - 2.33 ) ; P<0.001 ] . CONCLUSIONS Oral misoprostol is as effective as intramuscular oxytocin in the prevention of PPH . Shivering and transient pyrexia were specific side effects of misoprostol . Misoprostol has potential in reducing the high incidence of PPH in developing countries The objective of this trial was to investigate whether 500 ug oraJ misoprostol given immediately after delivery of the neonate at Caesarean section is as effective as a bolus intravenous injection of 10 iu Syntocinon in stimulating uterine contractions and thereby reducing blood loss OBJECTIVE To compare the efficacy and adverse effects of sublingual misoprostol , intravenous oxytocin , and intravenous methylergometrine in active management of the third stage of labor ( AMTSL ) . METHODS A double-blind r and omized trial of 300 women with a healthy singleton pregnancy allocated into 4 groups to receive either : 400 microg or 600 microg of sublingual misoprostol , 5 IU of intravenous oxytocin , or 200 microg of intravenous methylergometrine . The primary outcome measure was blood loss in the third and fourth stage of labor ; secondary measures were duration of the third stage of labor , changes in hemoglobin levels , and adverse effects . RESULTS Patients who received 600 microg of misoprostol had the lowest blood loss ( 96.05+/-21.1 mL ) , followed by 400 microg of misoprostol ( 126.24+/-49.3 mL ) , oxytocin ( 154.7+/-45.7 mL ) , and methylergometrine ( 223.4+/-73.7 mL ) ( P<0.01 ) . Shortest mean duration of the third stage of labor ( 5.74 minutes ) was with 600 microg of misoprostol , while methylergometrine had the longest ( 6.83 minutes ) ( P<0.05 ) . Pyrexia was observed in the misoprostol groups , and raised blood pressure in the methylergometrine group ( P<0.001 ) . The 24-hour postpartum hemoglobin level was similar among the groups ( P>0.05 ) . CONCLUSION Administration of 600 microg of sublingual misoprostol was more effective than 400 microg of misoprostol , intravenous oxytocin , and intravenous methylergometrine for AMTSL |
2,294 | 27,519,676 | Conclusion : These data suggest that healthy athletes who have no risk factors for degenerative joint disease may present fleeting quantitative alterations after running .
No irreversible , qualitative harmful effects seemed to occur , with the exception of persistent T1ρ elevation representing a proteoglycan depletion . | Background : Various studies have investigated structural knee changes after running , with conflicting results .
Purpose : To perform a systematic review of acute changes in knee structures as detected by magnetic resonance imaging ( MRI ) after running and assess the reversibility of these changes . | OBJECTIVE To assess differences in magnetic resonance imaging (MRI)-based compositional ( T2 ) and morphometric ( volume and thickness ) parameters of the tibio-femoral joint cartilage in subjects with and without osteoarthritis ( OA ) and compare these with clinical assessment tools during a 1-year follow-up . METHOD Three Tesla MRI of the knee joint was performed in eight female patients ( body mass index [ BMI ] > 30 ) with early OA and 10 age-matched female controls ( BMI < 30 ) at baseline ( BL ) and after 3 , 6 and 12 months . Cartilage T2 maps , volume and average thickness were calculated in five compartments ( medial/lateral femoral condyle , medial/lateral tibia and trochlea ) . These data were correlated with changes in clinical parameters and joint space width determined in st and ardized knee radiographs using a mixed r and om effects model . RESULTS At BL , T2 was significantly higher ( P<0.05 ) across the cartilage in patients ( 45.68+/-5.17ms ) compared to controls ( 41.75+/-4.33ms ) . Patients had significantly ( P<0.05 ) less cartilage volume and less average cartilage thickness in the tibia than controls ( 2.10+/-0.53cm(3 ) vs 2.91+/-0.49cm(3 ) and 1.59+/-0.24 mm vs 1.90+/-0.29 mm , respectively ) . A significant change in clinical parameters of OA , cartilage T2 values or a decrease of volume and average thickness could not be demonstrated within both groups . CONCLUSION Significant differences between the groups indicate that both T2 and morphometric parameters may be useful in quantifying early OA related changes . In a 12-month follow-up , however , no significant alterations of the studied parameters were found , which may be due to the length of the observation interval Purpose To prospect ively evaluate changes in T1rho and T2 relaxation time in the meniscus using 3.0 T MRI in asymptomatic knees of marathon runners and to compare these findings with those of age-matched healthy subjects . Material and methods Thirteen marathon runners underwent 3.0 T MRI including T1rho and T2 mapping sequences before , 48–72 h after , and 3 months after competition . Ten controls were examined at baseline and after 3 months . All images were analyzed by two musculoskeletal radiologists identifying and grading cartilage , meniscal , ligamentous . and other knee abnormalities with WORMS scores . Meniscal segmentation was performed to generate T1rho and T2 maps in six compartments . Results No differences in morphological knee abnormalities were found before and after the marathon . However , all marathon runners showed a significant increase in T1rho and T2 values after competition in all meniscus compartments ( p < 0.0001 ) , which may indicate changes in the biochemical composition of meniscal tissue . While T2 values decreased after 3 months T1rho values remained at a high level , indicating persisting changes in the meniscal matrix composition after a marathon . Conclusion T2 values in menisci have the potential to be used as biomarkers for identifying reversible meniscus matrix changes indicating potential tissue damage . T1rho values need further study , but may be a valuable marker for diagnosing early , degenerative changes in the menisci following exercise OBJECTIVE To longitudinally estimate the change in glycosaminoglycan content of knee cartilage in asymptomatic untrained female novice runners participating in a Start To Run program ( STR ) compared to sedentary controls . METHOD Nine females enrolling in a 10-week STR and 10 sedentary controls participated voluntarily . Prior to and after the 10-week period , both groups were subjected to dGEMRIC imaging . dGEMRIC indices of knee cartilage were determined at baseline and for the change after the 10-week period in both groups . Based on a self-reported weekly log , physical activity change during the study was depicted as decreased , unchanged or increased . The Mann-Whitney U and Kruskal-Wallis tests were applied to test the hypotheses that dGEMRIC changes occurred between groups and according to physical activity changes respectively . RESULTS No significant differences were established between groups for dGEMRIC indices at baseline ( P=0.541 ) . A significant positive change of the median dGEMRIC index in the runners group was demonstrated when compared to the controls [ + 11.66ms ( 95 % CI : -25.29 , 44.43 ) vs -9.56ms ( 95 % CI : -29.55 , 5.83 ) , P=0.006 ] . The change in dGEMRIC index differed significantly according to physical activity change ( P=0.014 ) , showing an increase in dGEMRIC index with increasing physical activity . CONCLUSION Since cartilage appears to positively respond to moderate running when compared to a sedentary lifestyle , this running scheme might be considered a valuable tool in osteoarthritis prevention strategies . Caution is warranted when applying these results to a wider population and to longer training periods OBJECTIVE To detect by magnetic resonance imaging ( MRI ) the presence and type of knee injuries in non-professional runners after running an ultra-marathon , and to determine whether ultra-marathon running exacerbates pre-existing knee injuries or results in new permanent injuries . DESIGN A prospect i ve MRI study of one knee of 10 r and omly selected participants who completed the Comrades Marathon between 1997 and 2002 . Their knees were scanned 48 hours before the race , and 48 hours and 1 month after the race . SETTING All scans were performed at the Radiology Department , Wentworth Hospital , Durban , and the University of KwaZulu-Natal . MAIN OUTCOME MEASURES Scores of all knee injuries detected on MRI scans immediately before the race , compared with the scores after the race . RESULTS All scanned knees demonstrated an abnormal amount of joint fluid before the race ; this increased immediately after the race in 5 runners and remained unchanged in another 5 . At 1 month , 5 knees showed decreased joint fluid and 5 remained unchanged , but these were not the same runners as in the post-race groups . There was increased signal intensity in the distal patellar and quadriceps tendons in 4 runners before the race , which increased or remained the same on post-race scans in 6 knees . There was a decrease in signal intensity on scans taken 1 month later in 3 runners , with complete resolution in 2 and no change in 1 . Old injuries to ligaments , tendons or other knee structures were unaffected by the race . No bone bruising , cartilage defects or meniscal abnormalities were observed . There was no significant difference in the pre- and post-race or 1-month scan scores . CONCLUSIONS The race appears to have had a detrimental effect on runners who started the ultra-marathon with tendinopathy , which worsened post-race by MRI criteria . One month after the race , the scan appearance of the overuse injury had either improved or resolved completely . Bone bruising or meniscal damage did not appear to occur , and the presence of increased joint fluid probably relates to stress or injury RATIONALE AND OBJECTIVES The authors performed this study to ( a ) measure changes in T2 relaxation rates , signal-to-noise ratio ( SNR ) , and contrast with sequential depletion of proteoglycan in cartilage ; ( b ) determine whether there is a relationship between the T2 relaxation rate and proteoglycan in cartilage ; and ( c ) compare the T2 mapping method with the spin-lattice relaxation time in the rotating frame ( T1rho ) mapping method in the quantification of proteoglycan-induced changes . MATERIAL S AND METHODS T2- and T1rho-weighted magnetic resonance ( MR ) images were obtained in five bovine patellae . All images were obtained with a 4-T whole-body MR unit and a 10-cm-diameter transmit-receive quadrature birdcage coil tuned to 170 MHz . T2 and T1rho maps were computed . RESULTS The SNR and contrast on the T2-weighted images were , on average , about 43 % lower than those on the corresponding T1rho-weighted images . The T2 relaxation rates varied r and omly without any particular trend , which yielded a poor correlation with sequential depletion of proteoglycan ( R2 = 0.008 , P < .70 ) . There was excellent linear correlation between the percentage of proteoglycan in the tissue and the T1rho relaxation rate ( R2 = 0.85 , P < .0001 ) . CONCLUSION T2-weighted imaging neither yields quantitative information about the changes in proteoglycan distribution in cartilage nor can be used for longitudinal studies to quantify proteoglycan-induced changes . T1rho-weighted imaging , however , is sensitive to sequential depletion of proteoglycan in bovine cartilage and can be used to quantify proteoglycan-induced changes Background Articular cartilage contributes to transferring enormous loads as uniformly as possible from one skeletal segment to the next . Whether it manages this task when subjected to the high repetitive loading cycles occurring during long-distance running and can remain intact is still the topic of controversy . Purpose To investigate the changes in cartilaginous volumes of the tibia , patella , and medial and lateral menisci after extreme dynamic loading as occurs in long-distance runners . Study Design Controlled laboratory study . Methods Forty-eight knees of male athletes were studied ( 38 ± 14 years ) . The subjects ran around a predetermined and precisely measured course ( 5 , 10 , 20 km ) , the beginning and end of the run being in the magnetic resonance imaging investigation room . The scan protocol was 60-minute rest period , first measurement , run , 3-minute delay , and second measurement . Results Overall , there were significant reductions in volume ( P < .05 ) for the patella , tibia , and menisci . There was evidence of significant change after a running distance of 5 km . A further statistical reduction of the volume could only be demonstrated for the medial meniscus after 10 and 20 km . Conclusion Tibial , patellar , and meniscal cartilaginous volumes show not only load-dependent volume changes but also an asymptotic curve . This is the first time that meniscal volume changes due to loading have been used as an indicator of the important mechanical contribution that the menisci make to sustaining the knee during repetitive loading . Clinical Relevance On the basis of the results of this study , the authors assume that the cartilage is able to adapt well to the loads caused by running Long distance running has become a fashionable recreational activity . This study investigated the effects of external impact loading on bone and cartilage introduced by performing a marathon race . Seven beginners were compared to six experienced recreational long distance runners and two professional athletes . All participants underwent magnetic resonance imaging of the hip and knee before and after a marathon run . Coronal T1 weighted and STIR sequences were used . The pre MRI served as a baseline investigation and monitored the training effect . All athletes demonstrated normal findings in the pre run scan . All but one athlete in the beginner group demonstrated joint effusions after the race . The experienced and professional runners failed to demonstrate pathology in the post run scans . Recreational and professional long distance runners tolerate high impact forces well . Beginners demonstrate significant changes on the post run scans . Whether those findings are a result of inadequate training ( miles and duration ) warrant further studies . We conclude that adequate endurance training results in adaptation mechanisms that allow the athlete to compensate for the stresses introduced by long distance running and do not predispose to the onset of osteoarthritis . Significant malalignment of the lower extremity may cause increased focal loading of joint and cartilage This prospect i ve study evaluated regular physical activity and self-reported physician-diagnosed osteoarthritis of the knee and /or hip joints among 16,961 people , ages 20 - 87 , examined at the Cooper Clinic between 1970 and 1995 . Among those aged 50 years and older , osteoarthritis incidence was higher among women ( 7.0 per 1000 person-years ) than among men ( 4.9 per 1000 person-years , P = 0.001 ) , while among those under 50 years of age , osteoarthritis incidence was similar between men ( 2.6 ) and women ( 2.7 ) . High levels of physical activity ( running 20 or more miles per week ) were associated with osteoarthritis among men under age 50 after controlling for body mass index , smoking , and use of alcohol or caffeine ( hazard ratio = 2.4 , 95 % CI : 1.5 , 3.9 ) , while no relationship was suggested among women or older men . These findings support the conclusion that high levels of physical activity may be a risk factor for symptomatic osteoarthritis among men under age 50 |
2,295 | 29,887,256 | It is concluded that there is support for paradoxical intention and cognitive therapy .
There are also other cognitive interventions that appears promising , such as cognitive refocusing and behavioral experiments .
We conclude that several cognitive treatment components and therapies can be viewed as efficacious or promising interventions for patients with insomnia disorder . | Since the beginning of the twenty-first century , there has been an increased focus on developing and testing cognitive components and therapies for insomnia disorder .
The aim of the current review was thus to describe and review the efficacy of cognitive components and therapies for insomnia . | Patients with primary insomnia overestimate their sleep onset latency ( SOL ) and underestimate their total sleep time ( TST ) . The present study aim ed to test the utility of a novel behavioural experiment design ed to correct distorted perception of sleep among patients diagnosed with primary insomnia . Individuals with primary insomnia were asked to wear an actigraph and keep a sleep diary for three nights . On the following day , half were shown the discrepancy between the data recorded on the actigraph and their sleep diary ( Shown-Discrepancy Group ) , the other half were not shown the discrepancy ( No-Demonstration Group ) . Participants were then asked to wear the actigraph and keep a sleep diary for three further nights . Following the behavioural experiment , the Shown-Discrepancy Group estimated their SOL more accurately and reported less anxiety and preoccupation about sleep compared to the No-Demonstration Group . The theoretical and clinical implication s of these findings are 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 Abstract Recent research in the treatment of insomnia by paradoxical intention has utilized two different methods of instruction . Studies utilizing the r and om assignment of subjects to treatment groups employ a procedure in which clients are provided with a straight-forward explanation based on the present authors ' underst and ing of the use of paradoxical intention with insomnia ( type A administration ) . In contrast , controlled case studies have employed reframing , a procedure which explains the need for the paradoxical intention in a manner which best suits the specific underst and ing of the individual client ( type B administration ) . The present study employed the type B method in a design employing the r and om assignment of clients to groups . Three additional groups ( type A administration , placebo control , no-treatment control ) completed the design . The results indicated that the type A method was superior to the type B procedure when the same method for administering paradoxical intention was applied to a r and omized group of individuals This investigation assessed the efficacy of a technique specifically design ed to change the style and content of presleep thoughts in order to reduce nighttime cognitive arousal and decrease insomnia severity . This investigation , termed " cognitive refocusing treatment for insomnia " ( CRT-I ) , previously improved sleep in a small sample of veterans with primary insomnia . In this investigation , university students with poor sleep were r and omly assigned to attend either one session of CRT-I and sleep hygiene education ( SH : n=27 ) or one session of only SH ( n=24 ) . Insomnia severity ( assessed by the Insomnia Severity Index ) and nighttime arousal ( assessed by the Pre-Sleep Arousal Scale ) were measured at baseline and 1month posttreatment . A significant Group × Time interaction for insomnia severity suggested more improved sleep over time for those receiving CRT-I+SH . A trend for a Group × Time interaction showed decreased cognitive arousal over time among those receiving CRT-I. These findings provide preliminary support for the efficacy of CRT-I for insomnia treatment among college students . Continued study of CRT-I in a community-based sample appears warranted It seems sensible to tailor treatments of insomnia in relation to the presenting characteristics of the sleeper and of the complaint . This report describes the first study formally to examine the comparative effectiveness of tailored and untailored ( r and omly allocated ) treatments . We developed a question naire to facilitate the design ing of individualized programmes . Results indicated that statistical analysis may underestimate the benefits of tailoring . Measures of clinical ly significant change , however , suggested that tailored treatment though it may be highly effective , is no more so than stimulus control therapy We describe the development of a cognitive therapy intervention for chronic insomnia . The therapy is based on a cognitive model which suggests that the processes that maintain insomnia include : ( 1 ) worry and rumination , ( 2 ) attentional bias and monitoring for sleep-related threat , ( 3 ) unhelpful beliefs about sleep , ( 4 ) misperception of sleep and daytime deficits and ( 5 ) the use of safety behaviors that maintain unhelpful beliefs . The aim of cognitive therapy for insomnia is to reverse all five maintaining processes during both the night and the day . In an open trial 19 patients meeting diagnostic criteria for primary insomnia were treated with cognitive therapy for insomnia . Assessment s were completed pretreatment , posttreatment and at 3- , 6- and 12-month followup . The significant improvement in both nighttime and daytime impairment evident at the posttreatment assessment was retained up to the 12 month followup Objective : To examine the mediators and the potential of treatment matching to improve outcome for cognitive behavior therapy ( CBT ) for insomnia . Method : Participants were 188 adults ( 117 women ; Mage = 47.4 years , SD = 12.6 ) meeting the Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ; text rev . ; DSM – IV – TR ; American Psychiatric Association [ APA ] , 2000 ) diagnostic criteria for chronic insomnia ( M duration : 14.5 years , SD : 12.8 ) . Participants were r and omized to behavior therapy ( BT ; n = 63 ) , cognitive therapy ( CT ; n = 65 ) , or CBT ( n = 60 ) . The outcome measure was the Insomnia Severity Index ( ISI ) . Hypothesized BT mediators were sleep-incompatible behaviors , bedtime variability ( BTv ) , risetime variability ( RTv ) and time in bed ( TIB ) . Hypothesized CT mediators were worry , unhelpful beliefs , and monitoring for sleep-related threat . Results : The behavioral processes mediated outcome for BT but not CT . The cognitive processes mediated outcome in both BT and CT . The subgroup scoring high on both behavioral and cognitive processes had a marginally significant better outcome if they received CBT relative to BT or CT . The subgroup scoring relatively high on behavioral but low on cognitive processes and received BT or CBT did not differ from those who received CT . The subgroup scoring relatively high on cognitive but low on behavioral processes and received CT or CBT did not differ from those who received BT . Conclusion : The behavioral mediators were specific to BT relative to CT . The cognitive mediators were significant for both BT and CT outcomes . Patients exhibiting high levels of both behavioral and cognitive processes achieve better outcome if they receive CBT relative to BT or CT alone Insomniacs commonly complain that they are unable to get to sleep at night due to unwanted thoughts , worries and concerns . The present study investigated whether brief training in identifying and elaborating an interesting and engaging imagery task for use during the pre-sleep period can reduce unwanted pre-sleep cognitive activity and sleep onset latency . Forty one people with insomnia were given one of three instructional sets to follow on the experimental night ; instructions to distract using imagery , general instructions to distract , or no instructions . Based on previous findings reported by Salkovskis & Campbell ( 1994 ) ' Behaviour Research and Therapy 32 ( 1994 ) 1 ' and ironic control theory ( Wegner , 1994 ) ' Psychological Review 101 ( 1994 ) 34 ' , it was predicted that ( 1 ) " imagery distraction " would be associated with shorter sleep onset latency and less frequent and distressing pre-sleep cognitive activity compared to the " no instruction " group and that ( 2 ) " general distraction " would be associated with longer sleep onset latency and more frequent and distressing pre-sleep cognitive activity compared to the " no instruction " group . Support was found for the first but not the second prediction . The success of the " imagery distraction " task is attributed to it occupying sufficient " cognitive space " to keep the individual from re-engaging with thoughts , worries , and concerns during the pre-sleep period . In addition , " imagery distraction " involved a very specific alternative cognitive task hence the operating process was given a feature positive search , conditions where mental control is likely to be achieved This study considers the role of pre-sleep cognitive arousal , worry , and inhibition in sleep onset difficulties . The Pennebaker writing task , which promotes emotional processing by asking people to write about their thoughts , worries , and emotions , has proven effective in several areas of health . Here , the paradigm 's ability to reduce pre-sleep cognitive arousal ( PSCA ) and sleep onset latency ( SOL ) in people with insomnia was tested . Twenty-eight people with insomnia were r and omized to three nights of Pennebaker writing or a control condition , following a one-night baseline . The outcomes of change over baseline at Day 4 in pre-sleep cognitive arousal and SOL were compared . Writing significantly reduced pre-sleep cognitive arousal on one out of two measures , but did not significantly reduce SOL A new cognitive therapy ( CT ) program was compared with an established behavioral treatment . Sixty-two patients meeting Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ; American Psychiatric Association , 1994 ) criteria for social phobia were r and omly assigned to CT , exposure plus applied relaxation ( EXP = AR ) , or wait-list ( WAIT ) . CT and EXP = AR were superior to WAIT on all measures . On measures of social phobia , CT led to greater improvement than did EXP = AR . Percentages of patients who no longer met diagnostic criteria for social phobia at posttreatment-wait were as follows : 84 % in CT , 42 % in EXP = AR , and 0 % in WAIT . At the 1-year follow-up , differences in outcome persisted . In addition , patients in EXP = AR were more likely to have sought additional treatment . Therapist effects were small and nonsignificant . CT appears to be superior to EXP = AR in the treatment of social phobia STUDY OBJECTIVES To compare the efficacy of problem-solving therapy ( PST ) combined with behavioral sleep strategies to st and ard cognitive therapy ( CT ) combined with behavioral sleep strategies in the treatment of insomnia . DESIGN A six-week r and omized controlled trial with one month follow-up . SETTING The Australian National University Psychology Clinic , Canberra , Australia . PARTICIPANTS Forty-seven adults aged 18 - 60 years recruited from the community meeting the Research Diagnostic Criteria for insomnia . INTERVENTIONS Participants received 6 weeks of treatment including one group session ( sleep education and hygiene , stimulus control instructions and progressive muscle relaxation ) followed by 5 weeks of individual treatment of PST or CT . MEASUREMENTS AND RESULTS Primary outcomes included sleep efficiency ( SE ) from sleep diaries , the Insomnia Severity Index ( ISI ) , and the Pittsburgh Sleep Quality Index ( PSQI ) . Secondary measures assessed dysfunctional sleep beliefs , problem-solving skills and orientations , and worry . Both treatments produced significant post therapy improvements in sleep which were maintained at 1 month follow-up ( on SE Cohen d = 1.42 , 95 % CI 1.02 - 1.87 for PST ; d = 1.26 , 95 % CI 0.81 - 1.65 for CT ; on ISI d = 1.46 , 95 % CI 1.03 - 1.88 for PST ; d = 1.95 , 95 % CI 0.52 - 2.38 for CT ; for PSQI d = 0.97 , 95 % CI 0.55 - 1.40 for PST and d = 1.34 , 95 % CI 0.90 - 1.79 for the CT ) . There were no differences in PST and CT in the size or rate of improvement in sleep although CT produced a significant faster rate of decline in negative beliefs about sleep than PST and there was a trend ( P = 0.08 ) for PST to produce a faster rate of improvement in negative problem orientation than CT . CONCLUSIONS The results provide preliminary support for problem solving treatment as an equally efficacious alternative component to cognitive therapy in psychological interventions for insomnia This study compared the effectiveness of paradoxical intention , stimulus control , information and a control group on severe sleep onset insomnia . Results showed that paradoxical intention and stimulus control were equally effective but significantly better than the information and control groups . It is suggested that treatment be adapted for each individual according to data collected from the intensive behavioral analysis of each case Patients with insomnia commonly complain that they are unable to get to sleep because of unwanted thoughts and worries . One account given of this excess cognitive activity is that it results from the incomplete processing of daytime stressors and hassles . Previous research has demonstrated the benefits of writing about emotional experiences as a method to facilitate emotional processing . This pilot study tested the hypothesis that writing about worries and concerns , with an emphasis on the expression and processing of emotion , will reduce sleep onset latency among an analogue sample of poor sleepers . Forty-two poor sleepers were r and omly allocated to 1 of 3 groups for 3 nights ; the instructions for the " problems " writing group emphasized the expression and processing of worries and concerns , the instructions for the " hobbies " writing group emphasized distraction from worries and concerns by writing about hobbies and interests , the " no writing " group were not given a writing task . The " problems " writing group reported shorter sleep onset latency compared to the " no writing " group . The results of this pilot study highlight the potential of research exploring the utility of a Pennebaker-style writing intervention for improving sleep Abstract A study by Turner and Ascher ( 1978 ) compared the efficacy of progressive relaxation , stimulus control , and paradoxical intention in ameliorating sleep onset insomnia . Results indicated that the three were equally effective . The present study is a partial replication of Turner and Ascher ( 1978 ) and focuses on the use of paradoxical intention in reducing sleep difficulties . Twenty-five individuals complaining of sleep discomfort were r and omly assigned to three groups : paradoxical intention , placebo control , no treatment control . Clients in the paradoxical intention group were instructed to remain awake while lying in bed in a darkened room . The complete rationale for such a prescription was provided . Those in the placebo group received a pseudo systematic desensitization program . Results indicated that subjects exposed to the paradoxical intention procedure reported significant improvement on several measures of sleep behavior when compared with reports of subjects in either placebo or no-treatment control groups BACKGROUND The usefulness of any diagnostic scheme is directly related to its ability to provide clinical ly useful information on need for care . In this study , the clinical usefulness of dimensional and categorical representations of psychotic psychopathology were compared . METHOD A total of 706 patients aged 16 - 65 years with chronic psychosis were recruited . Psychopathology was measured with the Comprehensive Psychopathological Rating Scale ( CPRS ) . Lifetime RDC , DSM-III-R , and ICD-10 diagnoses and ratings of lifetime psychopathology were made using OPCRIT . Other clinical measures included : ( i ) need for care ; ( ii ) quality of life ; ( iii ) social disability ; ( iv ) satisfaction with services ; ( v ) abnormal movements ; ( vi ) brief neuropsychological screen ; and ( vii ) over the last 2 years -- illness course , symptom severity , employment , medication use , self-harm , time in hospital and living independently . RESULTS Principal component factor analysis of the 65 CPRS items on cross-sectional psychopathology yielded four dimensions of positive , negative , depressive and manic symptoms . Regression models comparing the relative contributions of dimensional and categorical representations of psychopathology with clinical measures consistently indicated strong and significant effects of psychopathological dimensions over and above any effect of their categorical counterparts , whereas the reverse did not hold . The effect of psychopathological dimensions was mostly cumulative : high ratings on more than one dimension increased the contribution to the clinical measures in a dose-response fashion . Similar results were obtained with psychopathological dimensions derived from lifetime psychopathology ratings using the OCCPI . CONCLUSIONS A dimensional approach towards classification of psychotic illness offers important clinical advantages A sample of physician-referred chronic insomniacs was r and omly allocated to either progressive relaxation , stimulus control , paradoxical intention , placebo or no treatment conditions . Treatment process and outcome were investigated in terms of mean and st and ard deviation ( night to night variability ) measures of sleep pattern and sleep quality . Only active treatments were associated with significant improvement , but the nature of treatment gains varied . In particular , stimulus control improved sleep pattern , whereas relaxation affected perception of sleep quality . All improvements were maintained at 17 month follow-up . Results are discussed with reference to previous research and guidelines are given for clinical practice Abstract The importance of differences in pre-sleep cognitive intrusions in the treatment of sleep-onset insomnia were investigated . Twenty-four patients suffering from persistent psychophysiological insomnia were assessed on a pre-sleep cognitive intrusion inventory and divided into high and low scorers . Within these groups Ss were r and omly assigned to either a cognitively focused program ( cognitive restructuring . paradoxical instructions and thought stopping ) or a psychophysiologically focused method , EMG-biofeedback training . Patients were treated individually for 6 sessions . Within-group comparisons showed that both treatments yielded significant improvement in latency to falling asleep , pre-sleep tension , hours of sleep and sleep quality . Between-group comparisons showed a greater reduction of pre-sleep intrusions in patients treated by the cognitive method and of pre-sleep tension in patients trained in biofeedback , but no differential results were found in outcome variables either after treatments or at 3- and 12-month follow-ups . The results indicate that the use of differential treatments added little to the outcome of therapy , and do not support the hypothesis that greater benefits are gained when the treatment matches the patient 's cl aims of cognitive hyperarousal |
2,296 | 30,326,903 | Meta-regression showed that cohort study design , studies conducted in China , and publication before 2012 may be important influencing factors . | Background Low health literacy often has an association with poor health outcomes such as low levels of self-efficacy , increased mortality , poor health status and reduced quality of life ( QOL ) .
The aim of the study was to quantitatively evaluate the relationship between health literacy ( HL ) and QOL based on a systematic review and meta- analysis . | Background Although health literacy and quality of life are important concepts in health care , the link between them is unclear , especially for a population of frequent users of health care services with chronic diseases . Low health literacy is a common problem that has been linked to several negative health outcomes . Quality of life is an important health outcome in patient-centered care . Frequent users of health care services are a vulnerable population that deserves attention due to high costs and negative outcomes such as lower quality of life and higher mortality . The objective of this study was to examine the relationship between health literacy and the physical and mental components of quality of life among frequent users of health care services with chronic diseases . Methods This study presents the cross-sectional analysis of data collected through the V1SAGES project , a r and omized controlled trial on the effectiveness of a case management intervention in primary care in Quebec , Canada . Participants ( n = 247 ) were frequent users of health care services presenting at least one chronic condition . Health literacy was measured by the Newest Vital Sign ( NVS ) , and the physical and mental components of quality of life were evaluated by the Short Form Health Survey Version 2 ( SF-12v2 ) . The association between health literacy ( independent variable ) and the physical and mental components of quality of life was examined using biserial correlation . Results No association was found between health literacy and quality of life ( physical component : r = 0.108 , ρ = 0.11 ; mental component : r = 0.147 , ρ = 0.15 ) . Conclusion This study suggests that there is no relationship between health literacy and the physical and mental components of quality of life among frequent users of health care services . Trial registration NCT01719991 . Registered October 25 , 2012 Purpose The levels of health literacy in patients with long-term conditions ( LTCs ) are critical for better disease management and quality of life ( QoL ) . However , the impact of health literacy on QoL in older adults with LTCs is unclear . This study examined the association between health literacy and domains of QoL in older people with LTCs , investigating key socio-demographic and clinical variables , as confounders . Methods A prospect i ve cohort study was conducted on older adults ( n = 4278 ; aged 65 years and over ) with at least one LTC , registered in general practice s in Salford , UK . Participants completed measures of health literacy , QoL , multi-morbidity , depression , social support , and socio-demographic characteristics . Multivariate linear regressions were performed to examine the effects of health literacy on four QoL domains at baseline , and then changes in QoL over 12 months . Results At baseline , poor health literacy was associated with lower scores in all four QoL domains ( physical , psychological , social relationships and environment ) , after adjusting for the effects of multi-morbidity , depression , social support and socio-demographic factors . At 12-month follow-up , low health literacy significantly predicted declines in the physical , psychological and environment domains of QoL , but not in social relationships QoL. Conclusions This is the largest , most complete assessment of the effects of health literacy on QoL in older adults with LTCs . Low health literacy is an independent indicator of poor QoL older patients with LTCs . Interventions to improve health literacy in older people with LTCs are encouraged by these findings Background Limited evidence exists regarding the relationship between health literacy and health-related quality of life ( HRQoL ) in Australian patients from primary care . The objective of this study was to investigate the impact of health literacy on HRQoL in a large sample of patients without known vascular disease or diabetes and to examine whether the difference in HRQoL between low and high health literacy groups was clinical ly significant . Methods This was a cross-sectional study of baseline data from a cluster r and omised trial . The study included 739 patients from 30 general practice s across four Australian states conducted in 2012 and 2013 using the st and ard Short Form Health Survey ( SF-12 ) version 2 . SF-12 physical component score ( PCS-12 ) and mental component score ( MCS-12 ) are derived using the st and ard US algorithm . Health literacy was measured using the Health Literacy Management Scale ( HeLMS ) . Multilevel regression analysis ( patients at level 1 and general practice s at level 2 ) was applied to relate PCS-12 and MCS-12 to patient reported life style risk behaviours including health literacy and demographic factors . Results Low health literacy patients were more likely to be smokers ( 12 % vs 6 % , P = 0.005 ) , do insufficient physical activity ( 63 % vs 47 % , P < 0.001 ) , be overweight ( 68 % vs 52 % , P < 0.001 ) , and have lower physical health and lower mental health with large clinical ly significant effect sizes of 0.56 ( B ( regression coefficient ) = −5.4 , P < 0.001 ) and 0.78(B = -6.4 , P < 0.001 ) respectively after adjustment for confounding factors . Patients with insufficient physical activity were likely to have a lower physical health score ( effect size = 0.42 , B = −3.1 , P < 0.001 ) and lower mental health ( effect size = 0.37 , B = −2.6 , P < 0.001 ) . Being overweight tended to be related to a lower PCS-12 ( effect size = 0.41 , B = −1.8 , P < 0.05 ) . Less well-educated , unemployed and smoking patients with low health literacy reported worse physical health . Health literacy accounted for 45 and 70 % of the total between patient variance explained in PCS-12 and MCS-12 respectively . Conclusions Addressing health literacy related barriers to preventive care may help reduce some of the disparities in HRQoL. Recognising and tailoring health related communication to those with low health literacy may improve health outcomes including HRQoL in general practice OBJECTIVE To measure the level of functional health literacy ( FHL ) in an Australian population , and to explore the level of risk associated with level of FHL . DESIGN , SETTING AND PARTICIPANTS Cross-sectional , r and om population survey administered to 2824 South Australians aged > or=15 years , September-October 2008 . MAIN OUTCOME MEASURES Newest Vital Sign as a measure of FHL , self-reported general health status , and use of health services . RESULTS 24 % of respondents were at risk of limited FHL , and 21 % had a high likelihood of inadequate FHL ; this increased with age ( > or=65 years , 50 % v 25 - 44 years , 11 % ) . In multiple logistic regression models , a high likelihood of inadequate FHL was significantly more common among those with lower education ( left school < or=15 years of age , odds ratio [ OR ] , 8.1 ; 95 % CI , 4.8 - 13.6 ) ; with lower annual income ( < $ 20 000 , OR , 4.1 ; 95 % CI , 2.3 - 7.4 ) ; who were born in countries other than Australia , New Zeal and , the United Kingdom and Irel and ; and with poorer health status ( OR , 1.6 ; 95 % CI , 1.2 - 2.2 ) . Inadequate FHL was significantly less common among females ( OR , 0.6 ; 95 % CI , 0.5 - 0.8 ) . People with inadequate or at-risk FHL were significantly more likely to report having diabetes , cardiac disease or stroke , and significantly less likely to have recently attended a doctor . Respondents aged > or=65 years with inadequate FHL were more likely to have been admitted to hospital ( OR , 2.2 ; 95 % CI , 1.1 - 4.5 ) . CONCLUSION Many Australians are likely to have limited health literacy , and this is a risk to effective health care delivery and health improvement across the community Background Hypertension is a common and frequently occurring chronic disease of the cardiovascular system . Besides the pathological factors , the occurrence and exacerbation of hypertension are also associated with many factors of lifestyle and behaviors . Thus hypertensive patients ’ Health-related quality of life ( HRQL ) is not only influenced by the disease itself but also by many subjective factors such as health literacy and self-management efficacy , especially in the deeper part of southwestern China and thus is less developed compared to the other places . The purpose of this study was to examine the association between the HRQL of hypertensive patients and health literacy and self-management efficacy as well as how they affect the HRQL , so as to provide a theoretical reference for improving the HRQL of patients with hypertension in less developed areas . Methods This was a cross-sectional study of baseline data from a clustered r and omized controlled trial . The study design had passed a cross-national peer review and accepted grants by the China Medical Board . It was also registered in the Chinese Clinical Trial Registry (ChiCTR-OOR-14005563).A st and ardized question naire adapted from a previous vali date d WHO question naire was used for the survey which included detailed questions about patient ’s socio-demographic characteristics and self-reported information . Patients ’ HRQL was measured by the M and arin version of the 36-item Short Form . We used the vali date d M and arin version of the Self-Efficacy for Managing Chronic Disease 6-Item Scale to assess patients ’ self-management efficacy . The vali date d three-item Brief Health Literacy Screening ( BHLS ) was used to measure the patients ’ health literacy . A structural equation model was constructed , and p ≤ 0.05 was taken as significant . Results Demographic characteristics , health literacy and self-management efficacy have all significant effects on HRQL . Age , education level , self-management efficacy and health literacy were significantly related to the HRQL . The constructed model had a good fit for the data according to the model fit indices . Based on the model , health literacy ( r = 0.604 , p = 0.029 ) and Self-management efficacy ( r = 0.714 , p = 0.018 ) have a significant impact on HRQL . Demographic characteristics were inversely related to HRQL ( r = −0.419 , p = 0.007 ) , but have a significant impact on health literacy ( r = 0.675 , p = 0.029 ) and self-management efficacy ( r = 0.379 , p = 0.029 ) . At the same time , self-management efficacy was positively correlated to health literacy ( r = 0.413 , p < 0.01 ) . Conclusions Age , education level , self-management efficacy and health literacy were all related to the HRQL of patient with hypertension , which means that patients who are more elderly and have lower education level , low self-management efficacy and poor health literacy get worse HRQL . This may imply the necessary to introduce routine assessment of health literacy and self-management efficacy into assessment procedures for hypertensive patients ’ health management . Such assessment can help professionals to identify the population at greatest risk for poor health outcomes and low well-being in the future . In clinical practice , effective interventions such as direct guidance and education to raise the self-management efficacy and enhance health literacy might improve the HRQL of patients with hypertension . Trial registration Retrospectively registered Chinese Clinical Trial Registry (ChiCTR-OOR-14005563).Name of registry : Effects of the integrated delivery system and payment system of community-based intervention on rural patients of chronic diseases in Qianjiang District , China Date of registration : Retrospectively registered 23 November 2014 . Date of enrolment of the first participant to the trial : 5 July |
2,297 | 28,192,644 | High-certainty evidence shows that injection with cefuroxime with or without topical levofloxacin lowers the chance of endophthalmitis after surgery , and there is moderate-certainty evidence to suggest that using antibiotic eye drops in addition to antibiotic injection probably lowers the chance of endophthalmitis compared with using injections or eye drops alone . | BACKGROUND Endophthalmitis is a severe inflammation of the anterior or posterior ( or both ) chambers of the eye that may be sterile or associated with infection .
It is a potentially vision-threatening complication of cataract surgery .
Prophylactic measures for endophthalmitis are targeted against various sources of infection .
OBJECTIVES To evaluate the effects of perioperative antibiotic prophylaxis for endophthalmitis following cataract surgery compared with no prophylaxis or other form of prophylaxis . | The incidence of bacterial endophthalmitis has been 3 - 6 % after cataract extraction in the eye camps of South India from 1961 - 75 . During this time 50 791 cases were operated using systemic and topical chloramphenicol prophylaxis . This study evaluated the prophylactic intracameral injection of 50 microng of gentamicin in eye camp cataract extraction s. Only 6 of 1626 patients treated with intracameral gentamicin at operation developed bacterial endophthalmitis , an incidence of 0 - 37 % PURPOSE : To report results in the European Society of Cataract & Refractive Surgeons ( ESCRS ) multicenter study of the prophylaxis of endophthalmitis after cataract surgery . SETTING : Twenty‐four ophthalmology units and eye clinics in Austria , Belgium , Germany , Italy , Pol and , Portugal , Spain , Turkey , and the United Kingdom , with an administrative office in Irel and , coordinating center in Engl and , and data management and statistical unit in Scotl and . METHODS : This partially masked r and omized placebo‐controlled multinational clinical study to evaluate prospect ively the prophylactic effect of intracameral cefuroxime injection and /or perioperative levofloxacin eyedrops on the incidence of endophthalmitis after phacoemulsification cataract surgery began in September 2003 and was terminated early in January 2006 . The study used r and om allocation of patients in a 2 × 2 factorial design . RESULTS : By the end of 2005 , complete follow‐up records had been received for 13 698 study patients . Such a clear beneficial effect from the use of intracameral cefuroxime had been observed that it was agreed it would be unethical to continue the study and to wait for the completion of all follow‐up procedures before reporting this important result . If total reported cases of endophthalmitis are considered , the incidence rate observed in those treatment groups not receiving cefuroxime prophylaxis ( 23 cases in 6862 patients ) was almost 5 times as high ( odds ratio [ OR ] , 4.59 ; 95 % confidence interval [ CI ] , 1.74‐12.08 ; P = .002 ) as that in the groups receiving this treatment ( 5 cases in 6836 patients ) . If only cases proved to be due to infection are considered , the rate was more than 5 times as high ( OR , 5.32 ; 95 % CI , 1.55‐18.26 ; P = .008 ) in the treatment groups not receiving cefuroxime . Although the use of perioperative levofloxacin eyedrops as prophylaxis was also associated with a reduction in the observed incidence rate of postoperative endophthalmitis , this effect was smaller and was not statistically significant , whether total reported cases or only cases proven to be due to infection are used in calculating the rates . As not all follow‐up procedures are complete , it is possible that further cases of endophthalmitis may be reported ; however , it is not expected that this will alter the main conclusion . Nevertheless , it is anticipated that successful completion of follow‐up procedures in all patients will increase the total number in the study to approximately 16 000 . CONCLUSION : Intracameral cefuroxime administered at the time of surgery significantly reduced the risk for developing endophthalmitis after cataract surgery OBJECTIVE : To compare the efficacy and tolerability of a fixed combination of 0.3 % gatifloxacin and 1 % prednisolone ( Zypred ® ) versus the individual components used separately ( Zymar ® and Predfort ® ) for infection prophylaxis and inflammation control after cataract surgery with intraocular lens implantation . METHODS : A prospect i ve , r and omized , double-blind , parallel-group study of 108 patients who underwent phacoemulsification and intraocular lens implantation was conducted . After r and om assignment , 47 eyes received the fixed combination of topical 0.3 % gatifloxacin/1 % prednisolone drops , and 61 eyes received the same doses of the individual components as separate solutions four times a day for 15 days . Baseline and postoperative assessment s were made on postoperative days 1 , 7 , 15 , and 20 . RESULTS : All objective ( best corrected visual acuity , sign of active ocular inflammation , central and incisional corneal edema , the number of cells per high-power field in the anterior chamber , and intraocular pressure ) and subjective ( eye pain , photophobia , burning sensation , itching , and foreign body sensation ) criteria of efficacy were similar in both groups , with no significant differences . Group I included 47 eyes that received the fixed combination of gatifloxacin/prednisolone acetate eye drops and a placebo eye drop solution . Group II included 61 eyes that were treated with 0.3 % gatifloxacin and 1 % prednisolone acetate eye drops separately . The intraocular pressure was slightly higher in Group II ( p<0.05 ) . CONCLUSION : Treatment with the fixed-dose combination of gatifloxacin/prednisolone eye drops was as effective as the non-fixed combination in preventing infection and controlling inflammation after phacoemulsification and intraocular lens implantation IMPORTANCE Postoperative endophthalmitis ( POE ) often results in severe visual impairment . In clinical studies , an intracameral cefuroxime injection at the end of surgery was found to be effective at reducing the incidence of POE . Two important issues are the retinal safety of cefuroxime and its use for patients with perioperative capsular rupture where the risk of POE is dramatically increased . OBJECTIVE To assess the effectiveness and retinal safety of an intracameral injection of cefuroxime sodium for the prevention of POE and its possible use in cases of a perioperative capsular rupture of the lens . DESIGN , SETTING , AND PARTICIPANTS Population -based cohort study of patients 40 years of age or older who underwent cataract surgery at 1 of 1546 French health care facilities , public or private , and whose medical records were obtained from the national administrative data base . Data analyses were performed between March and November 2015 . MAIN OUTCOMES AND MEASURES The effectiveness and safety of the prophylactic injection of cefuroxime as measured by the incidence of POE and cystoid macular edema . RESULTS From January 2010 to October 2014 , a total of 3 351 401 eyes of 2 434 008 patients 40 years of age or older ( 58.9 % were women , and the mean [ SD ] age was 73.9 [ 9.5 ] years ) underwent cataract surgery ; 1941 patients ( 0.08 % ) developed POE during the 6 weeks after cataract surgery . The incidence of POE after cataract surgery decreased over the course of the study ( 0.11 % , 0.09 % , 0.08 % , 0.06 % , and 0.05 % in 2010 , 2011 , 2012 , 2013 , and 2014 , respectively [ P = .001 for trend ] ) as the use of cefuroxime prophylactic injections increased ( 11.1 % , 14.4 % , 32.8 % , 64.8 % , and 79.1 % in 2010 , 2011 , 2012 , 2013 , and 2014 , respectively [ P = .001 for trend ] ) . After multivariate adjustment , the risk of POE was reduced with the use of cefuroxime ( odds ratio , 0.61 [ 95 % CI , 0.56 - 0.68 ] ) . The retinal safety of an injection of cefuroxime , which was assessed by multiadjusted odds of retinal cystoid macular edema , was not increased for patients receiving cefuroxime injections ( odds ratio , 0.86 [ 95 % CI , 0.71 - 1.05 ] ) . For patients with a perioperative capsular rupture of the lens ( the major risk factor for POE ) , the incidence of POE was lower for those who received an injection of cefuroxime than for those who did not ( 0.37 % vs 0.51 % , respectively [ P = .001 ] ) , whereas an increased risk of cystoid macular edema was not identified for those who received or did not receive an injection of cefuroxime ( 5.6 % vs 7.3 % , respectively [ P = .12 ] ) . CONCLUSIONS AND RELEVANCE These data suggest that , in routine practice , the intracameral injection of cefuroxime at the conclusion of cataract surgery is associated with a lower risk of POE and is safe for patients with or without a perioperative capsular rupture . While these data might be used to support the consideration of its routine use to prevent POE , in the absence of a r and omized clinical trial , they can not prove a direct cause- and -effect relationship between the injection of cefuroxime and POE PURPOSE To compare intraoperative injection of triamcinolone and ciprofloxacin in a controlled-release system ( DuoCat ) with prednisolone and ciprofloxacin eye drops after cataract surgery . METHODS In this r and omized , double-masked , controlled trial , a total of 135 patients undergoing cataract surgery were r and omly allocated to two groups : 67 patients treated after surgery with prednisolone 1 % and ciprofloxacin 3 % eye drops four times daily ( week 1 ) , three times daily ( week 2 ) , twice daily ( week 3 ) , and once daily ( week 4 ) and 0.3 % ciprofloxacin drops four times daily ( weeks 1 and 2 ) , and 68 patients treated at the end of surgery with a sub-Tenon 's injection of 25 mg triamcinolone and 2 mg ciprofloxacin in biodegradable microspheres . The patients were examined on postoperative days 1 , 3 , 7 , 14 , and 28 . The main outcome measures were postoperative anterior chamber cell and flare , intraocular pressure ( IOP ) , lack of anti-inflammatory response , and presence of infection . RESULTS No significant differences were observed between the groups in anterior chamber cell ( P > 0.14 ) and flare ( P > 0.02 ) at any postoperative visits . The mean ( 99 % confidence interval ) differences in IOP between the prednisolone and triamcinolone groups on days 1 , 3 , 7 , 14 , and 28 were -0.4 mm Hg ( -2.1 to 1.3 ) , 0.0 mm Hg ( -1.4 to 1.3 ) , 0.0 mm Hg ( -1.1 to 1.1 ) , -0.2 mm Hg ( -1.1 to 0.8 ) , and -0.1 mm Hg ( -1.1 to 0.9 ) , respectively . No patient had a postoperative infection . CONCLUSIONS One injection of DuoCat had a therapeutic response and ocular tolerance that were equivalent to conventional eye drops in controlling inflammation after cataract surgery . ( Clinical Trials.gov number , NCT00431028 . ) Purpose To report the nationwide incidence and risk factors for endophthalmitis after cataract surgery in Sweden . Setting Swedish National Cataract Register containing reports on cataract operations from all Swedish ophthalmic surgical units . Design Prospect i ve epidemiologic study . Methods Endophthalmitis case reports were collected from 2005 through 2010 . Case and control parameters pertaining to patient characteristics and surgical technique were generated from the data base . In addition , information from annual surveys regarding the topical prophylactic protocol was analyzed . Results The reports showed 135 endophthalmitis cases in 464 996 operations , equaling an incidence of 0.029 % . Patient age over 85 years , perioperative communication with the vitreous and , above all , nonuse of intracameral cefuroxime showed a statistically significant association with endophthalmitis in the logistic regression . Short‐term topical antibiotics given as add‐on prophylaxis to the intracameral regimen before , after , or before and after the operation did not confer a clear‐cut benefit . Groups with topical treatment were small , comprising 14 % of the sample . Conclusions The incidence of endophthalmitis after cataract surgery in Sweden is declining , which appears to be explained by a fall in the frequency of major risk factors . Operating earlier in the cataract course , avoiding capsule breakage , and giving intracameral antibiotics universally should further reduce the endophthalmitis rate . Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned Purpose To compare two different postcataract surgery antibiotic/steroid therapeutic combinations , for clinical results as well as patient satisfaction . Methods Prospect i ve r and omized clinical trial of patients with bilateral operative cataract . Postoperatively , for 15 days one eye was r and omly assigned to therapy with the combination chloramphenicol 0.25%-betamethasone 0.13 % gel three times a day ( Group 1 ) and the other to the combination tobramycin 0.3%-dexamethasone 0.1 % eyedrops four times a day ( Group 2 ) . Results A total of 142 patients ( 284 eyes ) completed the study . The authors could not detect any significant difference between Group 1 and Group 2 concerning preoperative evaluation , surgical procedure , and complications . Pertaining to the two therapeutic regimens , efficacy , side effects , and clinical findings such as uncorrected visual acuity , intraocular pressure , edema or hyperemia of eyelids and /or conjunctiva , conjunctival and /or ciliary vessels congestion , decreased corneal transparency , corneal edema , Descemet folds , anterior chamber Tyndall and depth , and posterior synechiae were also comparable . Postoperative subjective pain and dry eye sensation were comparable between the two groups , while the gel preparation elicited a significantly more pleasant sensation in the patients ( p=0.04 ) . Conclusions The motivation for use of a gel is to prolong the permanence of associated drugs on the ocular surface , increasing potency and decreasing concentration of the drug and rate of administration . This in order to improve compliance and decrease potential side effects . Chloramphenicol 0.25%-betamethasone 0.13 % gel combination proved to have comparable efficacy , tolerance , and better acceptance by the patients than an aqueous tobramycin 0.3%-dexamethasone 0.1 % preparation Purpose To compare the efficacy of 2 prophylaxis regimens before cataract surgery using topical antibiotics ( 1 hour before surgery versus the day before ) , both with povidone – iodine , with regard to reducing the preoperative conjunctival bacterial load . Setting Tertiary ophthalmic referral center , Munich , Germany . Design Prospect i ve comparative case series . Methods Eyes were treated with topical antibiotics and their conjunctival sac flush irrigated using 10 mL of povidone – iodine 1.0 % . All eyes were r and omized to receive either 4 applications of topical 3500 IU/mL neomycin sulfate/6000 IU/mL polymyxin‐B sulfate within 1 hour preoperatively ( Group 1 ) or on the day before surgery ( Group 2 ) . Conjunctival specimens were obtained at 4 timepoints : T0C untreated fellow eye ( control ) , T0 surgery eye ( after antibiotic prophylaxis but before povidone – iodine irrigation ) , T1 after povidone – iodine , and T2 at the conclusion of surgery . All specimens were inoculated onto blood and chocolate – blood agar and into thioglycollate broth . Results One hundred thirty‐three eyes of 133 consecutive patients were included ( Group 1 , 64 eyes ; Group 2 , 69 eyes ) . The antibiotic regimens were equally effective in reducing the aerobic and microaerophilic conjunctival flora ( Group 1 , P=.028 ; Group 2 , P=.000 ) , but had no significant effect on anaerobic bacteria ( Group 1 , P=.201 ; Group 2 , P=.117 ) . Flush irrigation of the conjunctival sac using 10.0 mL povidone – iodine 1.0 % significantly decreased the conjunctival bacterial load in both groups . Conclusion Topical neomycin/polymyxin‐B was equally effective in reducing the conjunctival bacterial load whether given 1 day or 1 hour before surgery . The greatest effect was achieved by irrigating the conjunctival sac using povidone – iodine . Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned PURPOSE To establish the nationwide rate of postoperative endophthalmitis ( PE ) after cataract extraction ( CE ) and to study the relationship between PE and type of incision and other possible risk factors . DESIGN Prospect i ve , multicenter , comparative , nonr and omized , observational study . PARTICIPANTS All cataract surgeries in Sweden performed from January 2002 through December 2004 and all endophthalmitis cases in the same period that were reported to the Swedish National Cataract Register ( NCR ) . METHODS Through a st and ard reporting form sent to the NCR , patient and operation technique data were recorded . In addition , PE cases with a traceable number to the main register were collected . Various parameters with a possible impact on endophthalmitis development were evaluated . Univariate analyses and logistic regression were statistical methods . MAIN OUTCOME MEASURES The rate and etiology of PE ; possible risk factors pertaining to patient history and operation technique , with a special emphasis on incision type and location ; use of injector for the intraocular lens implantation ; kind of prophylaxis ; and presence of peroperative communication between the anterior chamber and vitreous . RESULTS The overall rate of PE was 0.048 % ( 109 cases in 225 471 CEs ) . Incidences of PE were 0.053 % with clear corneal incisions and 0.036 % with sclerocorneal incisions ( P = 0.14 , logistic regression analysis ) . The corresponding results were 0.040 % for superior incisions and 0.055 % for temporal incisions ( P = 0.14 ) . Communication between the anterior segment and vitreous was found to be a highly significant independent risk factor for PE ( P<0.001 ) , as were patient age > or = 85 years ( P<0.001 ) and the nonuse of intracameral cefuroxime ( P<0.001 ) . CONCLUSIONS The overall rate of PE after cataract surgery is low in Sweden , which may be a consequence of the widespread use of prophylactic intracameral cefuroxime . Only a trend for an increased risk of PE was detected for clear corneal and temporal wounds . The present data indicate that the use of clear corneal and /or temporal approaches will result in 1 additional PE case in approximately 5500 procedures on top of the PE rate after sclerocorneal or superior incisions , which was approximately 1 case in 2400 operations PURPOSE : To determine whether an intracameral injection of cefuroxime at the end of cataract surgery decreases the incidence of postoperative endophthalmitis . SETTING : Dupuytren Hospital , Ophthalmology Department , Limoges , France . DESIGN : Clinical trials . METHODS : Patients having cataract surgery between April 2003 and June 2008 were included in a survey of operative‐site infection . Intracameral cefuroxime injections started in June 2006 . Preoperative data ( beta‐lactam allergy , a history of endophthalmitis , age , sex ) , intraoperative data ( use of trypan blue , use of capsular ring or iris retractors , surgical time , senior or junior surgeon , corticosteroid injection , iris retractors ) , and the incidence of postoperative infections at 8 days and 1 month were prospect ively collected . RESULTS : During the inclusion period , 5115 patients had cataract surgery ; 2289 received cefuroxime and 2826 did not . The incidence of endophthalmitis was 35 ( 1.238 % ) of 2826 patients without intracameral cefuroxime and 1 ( 0.044 % ) of 2289 patients with intracameral cefuroxime ; the difference was statistically significant ( P<.0001 ) . No intraoperative factor was significantly associated with postoperative infection . No allergic reaction was reported . CONCLUSION : Intracameral cefuroxime injection at the end of cataract surgery was safe and significantly decreased the incidence of endophthalmitis . Financial Disclosure : No author has a financial or proprietary interest in any material or method mentioned OBJECTIVE The research ers sought to assess whether the widely used 1994 Cochrane Highly Sensitive Search Strategy ( HSSS ) for r and omized controlled trials ( RCTs ) in MEDLINE could be improved in terms of sensitivity , precision , or parsimony . METHODS A gold st and ard of 1,347 RCT records and a comparison group of 2,400 non-trials were r and omly selected from MEDLINE . Terms occurring in at least 1 % of RCT records were identified . Fifty percent of the RCT and comparison group records were r and omly selected , and the ability of the terms to discriminate RCTs from non-trial records was determined using logistic regression . The best performing combinations of terms were tested on the remaining records and in MEDLINE . RESULTS The best discriminating term was " Clinical Trial " ( Publication Type ) . In years where the Cochrane assessment of MEDLINE records had taken place , the strategies identified few additional unindexed records of trials . In years where Cochrane assessment has yet to take place , " R and omized Controlled Trial " ( Publication Type ) proved highly sensitive and precise . Adding six more search terms identified further , unindexed trials at reasonable levels of precision and with sensitivity almost equal to the Cochrane HSSS . CONCLUSIONS Most reports of RCTs in MEDLINE can now be identified easily using " R and omized Controlled Trial " ( Publication Type ) . More sensitive search es can be achieved by a brief strategy , the Centre for Review s and Dissemination/Cochrane Highly Sensitive Search Strategy ( 2005 revision ) Nonconcurrent analysis of 45,954 cataract operations performed by a single surgeon indicates that periocular injection of penicillin combined with multiple preoperative applications of topical chloramphenicol-sulphadimidine reduced the incidence of postoperative endophthalmitis by 72 % . Periocular penicillin alone was ineffective . A concurrent masked r and omized study of 6,618 cataract operations confirms the efficacy of combined prophylaxis and demonstrates that the topical regimen , by itself , is as ineffective as isolated penicillin prophylaxis PURPOSE : To present the development and design of the European Society of Cataract & Refractive Surgeons multicenter study of the prevention of postsurgical infective endophthalmitis after phacoemulsification and to describe the process for its successful implementation and conduct . SETTING : Twenty‐four ophthalmology units and eye clinics in Austria , Belgium , Germany , Italy , Pol and , Portugal , Spain , Turkey , and the United Kingdom , with an administrative office in Irel and , coordinating center in Engl and , and data management and statistical unit in Scotl and . METHODS : This partially masked r and omized placebo‐controlled multinational clinical study was design ed to evaluate prospect ively the prophylactic effect of intracameral cefuroxime and /or perioperative topical levofloxacin on postoperative endophthalmitis after cataract surgery . R and om allocation was based on a 2 × 2 factorial design that included participating centers as a class variable . Real‐time electronic data collection monitored study progress and provided weekly outcome tables , monthly recruitment summaries , and quarterly analytical reports for the study 's Data Monitoring Committee , which evaluated the safety and efficacy by Internet‐based conferences . RESULTS : A 2‐year lead time was required to meet harmonized st and ards of clinical research in the European Union , obtain ministerial authorization in 3 countries , gain institutional approvals at 24 hospitals , and procure indemnity insurance for surgical centers . Informed consent instruments , design ed to comply with national health policies , were translated into 8 language s. The use of information technology to collect study data enabled the organizers to evaluate individual eligibility at enrollment , adherence with study medications during and after surgery , and postoperative status during follow‐up . CONCLUSION : This international cooperative study provided the opportunity to estimate the current incidence of endophthalmitis after cataract surgery in Europe and determine whether 1 or both of 2 antimicrobial regimens reduces the risk for postsurgical intraocular infection OBJECTIVE To determine the safety of clear cornea cataract surgery using a self-sealing corneal tunnel incision . STUDY DESIGN Prospect i ve noncomparative consecutive case series . PARTICIPANTS A total of 3500 consecutive clear cornea topical anesthesia cataract surgeries performed by one surgeon between January 1994 and May 2003 were included . INTERVENTION All cases were operated using phacoemulsification via a temporal 3x2-mm clear cornea cataract incision under topical anesthesia . MAIN OUTCOME MEASURES Cases were evaluated for successful completion and postoperative endophthalmitis , retinal detachment ( RD ) , corneal decompensation , and wound complications requiring a return to the operating room . RESULTS All 3500 consecutive clear cornea cataract surgery cases performed under topical anesthesia were completed safely . A total of 56 cases ( 1.6 % ) required a suture due to wound leakage before completion of the surgery . No cases required a return to the operating room for suture placement . Six cases ( 0.17 % ) experienced an RD within a 30-day postoperative period . There were no cases of endophthalmitis or corneal decompensation detected . CONCLUSION For the past 9 years , we have found that clear cornea cataract surgery performed under topical anesthesia is safe and results in few postoperative complications PURPOSE : To identify risk factors and describe the effects of antibiotic prophylaxis on the incidence of postoperative endophthalmitis after cataract surgery based on analysis of the findings of the European Society of Cataract & Refractive Surgeons ( ESCRS ) multicenter study . SETTING : Twenty‐four ophthalmology units in Austria , Belgium , Germany , Italy , Pol and , Portugal , Spain , Turkey , and the United Kingdom . METHODS : A prospect i ve r and omized partially masked multicenter cataract surgery study recruited 16 603 patients . The study was based on a 2 × 2 factorial design , with intracameral cefuroxime and topical perioperative levofloxacin factors result ing in 4 treatment groups . The comparison of case and non‐case data was performed using multivariable logistic regression analyses . Odds ratios ( ORs ) associated with treatment effects and other risk factors were estimated . RESULTS : Twenty‐nine patients presented with endophthalmitis , of whom 20 were classified as having proven infective endophthalmitis . The absence of an intracameral cefuroxime prophylactic regimen at 1 mg in 0.1 mL normal saline was associated with a 4.92‐fold increase ( 95 % confidence interval [ CI ] , 1.87‐12.9 ) in the risk for total postoperative endophthalmitis . In addition , the use of clear corneal incisions ( CCIs ) compared to scleral tunnels was associated with a 5.88‐fold increase ( 95 % CI , 1.34‐25.9 ) in risk and the use of silicone intraocular lens ( IOL ) optic material compared to acrylic with a 3.13‐fold increase ( 95 % CI , 1.47‐6.67 ) . The presence of surgical complications increased the risk for total endophthalmitis 4.95‐fold ( 95 % CI , 1.68‐14.6 ) , and more experienced surgeons were more likely to be associated with endophthalmitis cases . When considering only proven infective endophthalmitis cases , the absence of cefuroxime and the use of silicone IOL optic material were significantly associated with an increased risk , and there was evidence that men were more predisposed to infection ( OR , 2.70 ; 95 % CI , 1.07‐6.8 ) . CONCLUSIONS : Use of intracameral cefuroxime at the end of surgery reduced the occurrence of postoperative endophthalmitis . Additional risk factors associated with endophthalmitis after cataract surgery included CCIs and the use of silicone IOLs Purpose To determine the efficacy of intraoperative antibiotic use in irrigating solutions on aqueous humor contamination during phacoemulsification surgery and to evaluate the corresponding risk of postoperative endophthalmitis . Methods 644 eyes of 640 patients who underwent phacoemulsification surgery with foldable intraocular lens ( IOL ) implantation were included in this study . Preoperative conjunctival smears were taken and eyes were allocated to receive irrigating infusion fluid containing either balanced salt solution (BSS)-only ( group 1 ; 322 eyes ) or BSS with antibiotics ( vancomycin and gentamycin ) during surgery ( group 2 ; 322 eyes ) . Bacterial contamination rates of aqueous humor sample s taken in the beginning and at the end of operation were compared . Predictive factors for the development of postoperative endophthalmitis were determined by clinical and microbiologic analyses . Results The rates of culture-positivity were similar between group 1 and group 2 for both preoperative conjunctival smears and aqueous sample s ( p > 0.05 ) . Aqueous sample s taken at the end of operation were found to be contaminated in 68 ( 21.1 % ) eyes in group 1 and 22 ( 6.8 % ) eyes in group 2 , and the difference was significant ( p = 0.0001 ; OR = 3.65 ( 2.1–6.0 ) ) . Capsular rupture was associated with higher rate of contamination in both groups ( p = 0.0001 ; OR = 7.7 and p = 0.0001 ; OR = 8.1 ) . Two eyes in the BSS-only group developed postoperative endophthalmitis and these cases had posterior capsular rupture during the surgery and culture-positivity forstaphylococcus epidermidis throughout the study . Conclusions Intraoperative antibiotic irrigation decreases aqueous humor contamination during phacoemulsification . Further studies are warranted to determine the interrelationship between aqueous humor contamination and endophthalmitis in eyes with posterior capsular rupture A r and omized , controlled , prospect i ve comparison of the effectiveness of anterior and posterior injections of antibiotics in the prevention of endophthalmitis following cataract extraction was carried out in a village hospital in Pakistan . The study involved 77,015 cataract operations performed mainly by two surgeons . Anterior subTenon injections ( " subconjunctival " ) and posterior subTenon injections ( " retrobulbar " ) were equally effective in preventing postoperative infection PURPOSE : To assess the relationship between the risk for acute endophthalmitis after cataract extraction and whether certain factors , such as surgeon qualification , numerical order , duration of surgery , operating theater , and type of anesthesia ( topical or retrobulbar ) , could be modified to decrease the risk . SETTING : Single‐center academic practice . METHODS : Two epidemiological studies were performed : a case‐control study and a retrospective cohort study . The surgical records of all patients with clinical ly diagnosed endophthalmitis within 30 days after cataract surgery performed between February 2002 and September 2003 were review ed . The endophthalmitis cases were compared with 108 r and omly selected controls ( 4 controls per case ) . The global incidence of endophthalmitis and the incidence according to type of anesthesia were calculated . RESULTS : Of 5011 cataract extraction s performed , 27 cases of endophthalmitis occurred . The incidence was 5.39 per 1000 procedures . An independent statistically significant relationship was found between endophthalmitis and the use of topical anesthesia ( odds ratio [ OR ] , 11.8 ; 95 % confidence interval [ CI ] , 2.4‐58.7 ) and surgery longer than 45 minutes ( OR , 7.2 ; 95 % CI , 1.7‐29.7 ) but not between the other variables . The incidence of endophthalmitis was 1.8 per 1000 cataract extraction s with retrobulbar anesthesia and 6.76 per 1000 with topical anesthesia ( relative risk [ RR ] , 3.76 ; 95 % CI , 0.89‐15.85 ) . After the start of the study period was extended to May 2001 , the incidence of endophthalmitis was 1.3 per 1000 cataract extraction s with retrobulbar anesthesia and 8.7 per 1000 with topical anesthesia ( RR , 6.72 ; 95 % CI , 1.63‐27.63 ) . CONCLUSION : Results suggest that there may be an association between topical anesthesia and endophthalmitis after cataract extraction OBJECTIVE To determine the prevalence and causes of low vision in a large sample of nursing home residents . METHODS Twenty-eight nursing homes on the Eastern Shore of Maryl and and Delaware were enrolled in a clinical trial to assess the impact of vision restoration/rehabilitation on nursing home residents . Visual acuity was measured using both recognition charts and preferential looking techniques . An ophthalmologist examined all residents with visual acuity worse than 20/40 in the better-seeing eye and determined the primary cause for decreased vision . Results are reported for the better-seeing eye . RESULTS Of 2544 eligible residents , 1591 ( 63 % ) participated , but 286 residents were unable to respond to visual acuity testing . Of the remaining 1307 residents , 496 ( 37 % ) had best-corrected visual acuity worse than 20/40 in the better-seeing eye . Causes were ascribed for 412 subjects . Rates of low vision were similar between African American subjects and white subjects ( 39 % and 38 % , respectively ; age-adjusted P = .18 ) . Cataract was the leading cause of low vision , responsible for 37 % of low vision among white subjects and 54 % of low vision among African American subjects . Macular degeneration was responsible for 29 % of low vision among white subjects but only 7 % among African American subjects . Glaucoma caused low vision in 4 % of white subjects and 10 % of African American subjects . Refractive error was not a frequent cause of low vision in nursing home residents . CONCLUSIONS Low vision is highly prevalent among nursing home residents , with 37 % having visual acuity worse than 20/40 in the better-seeing eye . Differences in causes of low vision between African American subjects and white subjects were noted , with African American subjects more likely to have vision loss on the basis of cataract , a readily treated condition . Appropriate interventions for nursing home residents , who face significant obstacles in accessing eye care services , have the potential to improve the quality of life of this at-risk older population PURPOSE : To determine the differences in the endophthalmitis rates in cataract surgery before and after prophylactic use of intracameral cefuroxime . SETTING : University Hospital Fundación Alcorcón , Madrid , Spain . METHODS : This prospect i ve study evaluated patients who had cataract surgery at a university eye center over a 10‐year period ( 1999 to 2008 ) . Since the protocol 's approval by the Hospital Board in October 2005 to the end of the 10‐year period , cataract patients were routinely treated with prophylactic intracameral cefuroxime . A data base was used to measure the occurrence of endophthalmitis postoperatively . Then , the incidence of endophthalmitis before and after generalized use of prophylactic cefuroxime was compared . The effect of cefuroxime was evaluated by the relative risk . RESULTS : From January 1999 to December 2008 , 13 652 patients had cataract surgery . Forty‐two cases of postoperative bacterial endophthalmitis were reported . The endophthalmitis rate was 0.30 % ( 95 % confidence interval [ CI ] , 0.26%‐0.35 % ) overall , 0.59 % ( 95 % CI , 0.50%‐0.70 % ) from January 1999 to September 2005 , and 0.043 % ( 95 % CI , 0.02%‐0.06 % ) from October 2005 to December 2008 . The relative risk was 0.07 ( range 0.022 to 0.231 ; P<.05 ) . CONCLUSION : Intracameral cefuroxime proved to be effective in reducing the risk for acute‐onset endophthalmitis after cataract surgery . Financial Disclosure : No author has a financial or proprietary interest in any material or method mentioned The authors conducted an open-label nonr and omized parallel trial to examine whether the preoperative application of povidone-iodine to the ocular surface reduces the incidence of endophthalmitis after intraocular surgery . During an 11-month period , topical 5 % povidone-iodine was used to prepare the conjunctiva in 1 set of 5 operating rooms , while silver protein solution was used in another set of 5 rooms . In all cases , surgeons continued to use their customary prophylactic antibiotics . A significantly lower incidence of culture-positive endophthalmitis ( P less than 0.03 ) was observed in the operating rooms using povidone-iodine ( 2 of 3489 or 0.06 % ) compared with those using silver protein solution ( 11 of 4594 or 0.24 % ) . Use of topical povidone-iodine in over 3000 cases was not associated with any adverse reactions . In a majority of the observed cases of endophthalmitis , some form of intraoperative communication with the vitreous cavity existed Purpose To evaluate corneal endothelial changes after intracameral injection of vancomycin at the end of routine cataract surgery . Setting Department of Ophthalmology , Hospital Virgen de los Lirios , Alcoy , Alicante , Spain . Design Prospect i ve comparative case series . Methods Eyes received an intracameral injection of vancomycin ( 1 mg/0.1 mL ) or cefuroxime ( 1 mg/0.1 mL ) at the end of surgery . The visual acuity , corneal clarity , pachymetry , anterior chamber reaction , endothelial cell density ( ECD ) , coefficient of variation ( CoV ) , and hexagonality were evaluated at baseline and 1 week , 1 month , and 3 months after surgery . Results Sixty eyes ( 42 patients ) , 30 in each group , were enrolled . In the vancomycin group , there was a significant decrease in ECD 1 week after surgery ( P = .000 ) , after which the ECD stabilized . There were no statistically significant changes in postoperative CoV values between preoperatively and postoperatively , although there was a transient decrease in hexagonality 1 week after surgery ( P = .006 ) . In the cefuroxime group , the ECD significantly decreased 1 week after surgery ( P = .000 ) and then stabilized . There was a statistically significantly decrease in the CoV between preoperatively and 3 months postoperatively ( P = .014 ) . No changes were noted in hexagonality . The postoperative ECD , CoV , and hexagonality values were not significantly different between the vancomycin group and the cefuroxime group . Conclusions Endothelial cell changes observed after intracameral vancomycin were similar to those observed after intracameral cefuroxime in cataract surgery . The results indicate that intracameral vancomycin is safe for use in cataract surgery . Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned |
2,298 | 28,476,404 | The adverse effects most associated with dropout were attempted suicide followed by mania , skin rash , and headache .
Problems relating to clinical trials and family arbitration were also related with dropout .
Selective serotonin reuptake inhibitors were linked to the lowest prevalence , probably due to fewer perceived problems with related adverse effects and higher efficacy in adolescents .
Cognitive-behavioral therapy combined with pharmacotherapy produced a lower nonadherence prevalence ; this approach can be an alternative to avoid dropouts and relapse . | PURPOSE Depression currently affects 350 million people , and its prevalence among adolescents is 4 % to 8 % .
Adolescents who ab and on antidepressant treatment or drop out of clinical trials are less likely to recover or experience a remission of symptoms because they are not being followed up by a medical team .
The objective of this study was to analyze the dropout rates of r and omized clinical trials of depressed adolescents receiving treatment with antidepressant drugs and the factors associated with nonadherence by summarizing this information in a systematic review and meta- analysis . | BACKGROUND There is great heterogeneity of clinical presentation and outcome in paediatric depression . AIMS To identify which clinical and environmental risk factors at baseline and during treatment predicted major depression at 28-week follow-up in a sample of adolescents with depression . METHOD One hundred and ninety-two British adolescents with unipolar major depression were enrolled in a r and omised controlled trial ( the Adolescent Depression Antidepressants and Psychotherapy Trial , ADAPT ) . Participants were treated for 28 weeks with routine psychosocial care and selective serotonin reuptake inhibitors ( SSRIs ) , with half also receiving cognitive-behavioural therapy ( CBT ) . Full clinical and demographic assessment was carried out at baseline and 28 weeks . RESULTS Depression at 28 weeks was predicted by the additive effects of severity , obsessive-compulsive disorder and suicidal ideation at entry together with presence of at least one disappointing life event over the follow-up period . CONCLUSIONS Clinicians should assess for severity , suicidality and comorbid obsessive-compulsive disorder at presentation and should monitor closely for subsequent life events during treatment OBJECTIVE Open-label trials with the selective serotonin reuptake inhibitor citalopram suggest that this agent is effective and safe for the treatment of depressive symptoms in children and adolescents . The current study investigated the efficacy and safety of citalopram compared with placebo in the treatment of pediatric patients with major depression . METHOD An 8-week , r and omized , double-blind , placebo-controlled study compared the safety and efficacy of citalopram with placebo in the treatment of children ( ages 7 - 11 ) and adolescents ( ages 12 - 17 ) with major depressive disorder . Diagnosis was established with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version . Patients ( N=174 ) were treated initially with placebo or 20 mg/day of citalopram , with an option to increase the dose to 40 mg/day at week 4 if clinical ly indicated . The primary outcome measure was score on the Children 's Depression Rating Scale-Revised ; the response criterion was defined as a score of < or = 28 . RESULTS The overall mean citalopram dose was approximately 24 mg/day . Mean Children 's Depression Rating Scale-Revised scores decreased significantly more from baseline in the citalopram treatment group than in the placebo treatment group , beginning at week 1 and continuing at every observation point to the end of the study ( effect size=2.9 ) . The difference in response rate at week 8 between placebo ( 24 % ) and citalopram ( 36 % ) also was statistically significant . Citalopram treatment was well tolerated . Rates of discontinuation due to adverse events were comparable in the placebo and citalopram groups ( 5.9 % versus 5.6 % , respectively ) . Rhinitis , nausea , and abdominal pain were the only adverse events to occur with a frequency exceeding 10 % in either treatment group . CONCLUSIONS In this population of children and adolescents , treatment with citalopram reduced depressive symptoms to a significantly greater extent than placebo treatment and was well tolerated OBJECTIVE To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression . METHOD After a 7- to 14-day screening period , 275 adolescents with major depression began 8 weeks of double-blind paroxetine ( 20 - 40 mg ) , imipramine ( gradual upward titration to 200 - 300 mg ) , or placebo . The two primary outcome measures were endpoint response ( Hamilton Rating Scale for Depression [ HAM-D ] score < or = 8 or > or = 50 % reduction in baseline HAM-D ) and change from baseline HAM-D score . Other depression-related variables were ( 1 ) HAM-D depressed mood item ; ( 2 ) depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version ( K-SADS-L ) ; ( 3 ) Clinical Global Impression ( CGI ) improvement scores of 1 or 2 ; ( 4 ) nine-item depression subscale of K-SADS-L ; and ( 5 ) mean CGI improvement scores . RESULTS Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score < or = 8 , HAM-D depressed mood item , K-SADS-L depressed mood item , and CGI score of 1 or 2 . The response to imipramine was not significantly different from placebo for any measure . Neither paroxetine nor imipramine differed significantly from placebo on parent- or self-rating measures . Withdrawal rates for adverse effects were 9.7 % and 6.9 % for paroxetine and placebo , respectively . Of 31.5 % of subjects stopping imipramine therapy because of adverse effects , nearly one third did so because of adverse cardiovascular effects . CONCLUSIONS Paroxetine is generally well tolerated and effective for major depression in adolescents OBJECTIVE To examine the course of depression during the treatment of adolescents with depression who had recently attempted suicide . METHOD Adolescents ( N = 124 ) , ages 12 to 18 years , with a 90-day history of suicide attempt , a current diagnosis of depressive disorder ( 96.0 % had major depressive disorder ) , and a Children 's Depression Rating Scale-Revised ( CDRS-R ) score of 36 or higher , entered a 6-month treatment with antidepressant medication , cognitive-behavioral therapy focused on suicide prevention , or their combination ( Comb ) , at five academic sites . Treatment assignment could be either r and om or chosen by study participants . Intent-to-treat , mixed effects regression models of depression and other relevant ratings were estimated . Improvement and remission rates were computed with the last observation carried forward . RESULTS Most patients ( n = 104 or 84 % ) chose treatment assignment , and overall , three fourths ( n = 93 ) received Comb . In Comb , CDRS-R declined from a baseline adjusted mean of 49.6 ( SD 12.3 ) to 38.3 ( 8.0 ) at week 12 and to 27.0 ( 10.1 ) at week 24 ( p < .0001 ) , with a Clinical Global Impression -defined improvement rate of 58.0 % at week 12 and 72.2 % at week 24 and a remission ( CDRS-R ≤ 28 ) rate of 32.5 % at week 12 and 50.0 % at week 24 . The CDRS-R and the Scale for Suicidal Ideation scores were correlated at baseline ( r = 0.43 , p < .0001 ) and declined in parallel . CONCLUSIONS When vigorously treated with a combination of medication and psychotherapy , adolescents with depression who have recently attempted suicide show rates of improvement and remission of depression that seem comparable to those observed in nonsuicidal adolescents with depression BACKGROUND Psychiatric clinics have high non-attendance rates and failure to attend may be a sign of deteriorating mental health . AIMS To investigate why psychiatric out- patients fail to attend , and the outcome of attenders and non-attenders . METHOD Prospect i ve cohort study of r and omly selected attenders and non-attenders at general adult psychiatric out-patient clinics . Subjects were interviewed at recruitment and severity of mental disorder and degree of social adjustment were measured . Six and 12 months later their engagement with the clinic and any psychiatric admissions were ascertained . RESULTS Of the 365 patients included in the study , 30 were untraceable and 224 consented to participate . Follow-up patients were more psychiatrically unwell than new patients . For follow-up patients , non-attenders had lower social functioning and more severe mental disorder than those who attended . At 12-month follow-up patients who missed their appointment were more likely to have been admitted than those who attended . CONCLUSIONS Those who miss psychiatric follow-up out-patient appointments are more unwell and more poorly socially functioning than those who attend . They have a greater chance of drop-out from clinic contact and subsequent admission Our recent 8-week , r and omized , placebo-controlled trial of fluoxetine in adolescents ( ages 12 - 17 years ) with comorbid depression and substance use disorder ( SUD ) did not detect a significant antidepressant treatment effect . The purpose of this secondary analysis was to explore moderators of the effect of fluoxetine in this sample . Static moderators measured at baseline were depression chronicity and hopelessness severity ; time-varying moderators measured at baseline and weekly during the 8-week trial period were alcohol and marijuana use severity . Treatment effects on depression outcomes were examined among moderating subgroups in r and om effects regression models . Subjects assigned to fluoxetine treatment with chronic depression at baseline ( p = .04 ) or no more than moderate alcohol use during the trial ( p = .04 ) showed significantly greater decline in depression symptoms in comparison to placebo-assigned subgroups . The current analysis suggests that youth with chronic depression and no more than moderate alcohol consumption are likely to respond better to treatment with fluoxetine compared with placebo than youth with transient depression and heavy alcohol use OBJECTIVE A r and omized , double-blind , placebo-controlled flexible-dose , parallel group trial was conducted at 26 clinical investigational sites in the United States to examine the safety and efficacy of the selegiline transdermal system ( STS ) ( EMSAM ® ) in adolescents ( ages 12 - 17 years ) meeting American Psychiatric Association , Diagnostic and Statistical Manual of Mental Disorders , 4th ed . ( DSM-IV ) criteria for moderate to severe major depressive disorder ( MDD ) without psychotic features . METHODS Adolescents ( n=308 ) with moderate to severe MDD were r and omized to either STS ( n=152 ) or placebo ( n=156 ) . Two hundred and fifteen ( 69.8 % ) subjects completed the study and 17 ( 5.5 % ) reported discontinuation because of adverse events ( AEs ) . The primary efficacy outcome measure was the mean change from baseline to end of study ( week 12 last observation carried forward [ LOCF ] ) in the Children 's Depression Rating Scale-Revised ( CDRS-R ) total score . Secondary outcome measures included end-point Clinical Global Impressions - Severity ( CGI-S ) and Clinical Global Impressions - Improvement ( CGI-I ) . RESULTS Patients on STS or placebo had a significant decline from baseline ( p<0.001 ) on their CDRS-R total score with mean reductions±SD as follows : STS 21.4±16.6 ; placebo 21.5±16.5 . Both groups had similar response rates ( 58.6 % vs. 59.3 % ) defined as CGI-I of 1 or 2 at study end . However , these between-group efficacy findings were without statistical significance . The overall incidence of reported AEs was 62.5 % for STS-treated patients and 57.7 % for placebo-treated patients . Most commonly reported AEs in STS or placebo groups were application site reactions ( STS=24.3 % ; placebo=21.8 % ) , headache ( STS=17.1 % ; placebo=16.7 % ) , and nausea ( STS=7.2 % ; placebo=7.7 % ) . Treatment groups did not differ on any laboratory parameters , vital signs , or electrocardiogram ( ECG ) findings . No suspected hypertensive crises were reported in the trial . CONCLUSIONS These data demonstrated that the STS was safe and well tolerated in this adolescent sample . However , both STS-treated and placebo-treated subjects demonstrated a decline from baseline in depressive symptoms ( CDRS-R total score ) over the length of the study , without statistical superiority by either group OBJECTIVE To determine amitriptyline 's ( AMI ) efficacy in the acute treatment of adolescent major depressive disorder ( MDD ) . METHOD Subjects aged 12 through 17 years meeting Research Diagnostic Criteria for MDD , diagnosed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children ( K-SADS ) , participated in a 2-week placebo-washout followed by an 8-week , r and omized , double-blind , parallel- design , placebo-controlled trial of AMI , 5 mg/kg per day . The K-SADS nine-item scale , the Hamilton Depression Rating Scale , and the Clinical Global Impressions rating scale were used as outcome measures . RESULTS Thirty-one subjects were r and omized ( 18 AMI , 13 placebo ) . Twenty-two subjects were study completers ( 12 AMI , 10 placebo ) . AMI 's efficacy was suggested by the Clinical Global Impressions but not the K-SADS-derived data . Perhaps the primary limitation of the current study is its small sample size . CONCLUSION No definitive recommendation can be made regarding the efficacy of tricyclic antidepressants in the treatment of adolescent MDD OBJECTIVE The safety , efficacy , and tolerability of venlafaxine extended release ( ER ) in subjects ages 7 to 17 years with major depressive disorder were evaluated in two multicenter , r and omized , double-blind , placebo-controlled trials conducted between October 1997 and August 2001 . METHOD Participants received venlafaxine ER ( flexible dose , based on body weight ; intent to treat , n = 169 ) or placebo ( intent to treat , n = 165 ) for up to 8 weeks . The primary efficacy variable was the change from baseline in the Children 's Depression Rating Scale-Revised score at week 8 . RESULTS There were no statistically significant differences between venlafaxine ER and placebo on the Children 's Depression Rating Scale-Revised in either study . A post hoc age subgroup analysis of the pooled data showed greater improvement on the Children 's Depression Rating Scale-Revised with venlafaxine ER than with placebo ( -24.4 versus -19.9 ; p = .022 ) among adolescents ( ages 12 - 17 ) , but not among children ( ages 7 - 11 ) . The most common adverse events were anorexia and abdominal pain . Hostility and suicide-related events were more common in venlafaxine ER-treated participants than in placebo-treated participants . There were no completed suicides . CONCLUSIONS Venlafaxine ER may be effective in depressed adolescents . However , its safety and efficacy in pediatric patients has not been established . Prescribers should monitor for signs of suicidal ideation and hostility in pediatric patients taking venlafaxine ER To evaluate how well a blind is maintained in a double-blind study . Clinicians ( n = 66 ) , parents ( n = 62 ) , and depressed child/adolescent subjects ( n = 62 ) predicted whether the patient had been on either placebo or active medication at the end of an eight-week double-blind placebo versus fluoxetine trial . Clinician , patient and parents ’ guesses as to which treatment they had received were at a chance level based on an overall analysis . However , when clinical response and condition assignment were controlled , all were correctly predicting placebo treatment but not medication treatment . The finding that subjects , parents and clinicians predict at a chance level is important for double-blind study design integrity . However , clinicians , parents and subjects were accurately predicting placebo treatment when clinical response and the assigned condition were taken into account but not medication . Since they do not know condition however , all remain essentially blinded , and this is an important finding for design and analysis integrity for double-blind studies OBJECTIVE The authors evaluated a sequential treatment strategy of fluoxetine and relapse-prevention cognitive-behavioral therapy ( CBT ) to determine effects on remission and relapse in youths with major depressive disorder . METHOD Youths 8 - 17 years of age with major depression were treated openly with fluoxetine for 6 weeks . Those with an adequate response ( defined as a reduction of 50 % or more on the Children 's Depression Rating Scale-Revised [ CDRS-R ] ) were r and omly assigned to receive continued medication management alone or continued medication management plus CBT for an additional 6 months . The CBT was modified to address residual symptoms and was supplemented by well-being therapy . Primary outcome measures were time to remission ( with remission defined as a CDRS-R score of 28 or less ) and rate of relapse ( with relapse defined as either a CDRS-R score of 40 or more with a history of 2 weeks of symptom worsening , or clinical deterioration ) . RESULTS Of the 200 participants enrolled in acute-phase treatment , 144 were assigned to continuation treatment with medication management alone ( N=69 ) or medication management plus CBT ( N=75 ) . During the 30-week continuation treatment period , time to remission did not differ significantly between treatment groups ( hazard ratio=1.26 , 95 % CI=0.87 , 1.82 ) . However , the medication management plus CBT group had a significantly lower risk of relapse than the medication management only group ( hazard ratio=0.31 , 95 % CI=0.13 , 0.75 ) . The estimated probability of relapse by week 30 was lower with medication management plus CBT than with medication management only ( 9 % compared with 26.5 % ) . CONCLUSIONS Continuation-phase relapse-prevention CBT was effective in reducing the risk of relapse but not in accelerating time to remission in children and adolescents with major depressive disorder OBJECTIVE To investigate side effects , medication compliance , and assumption of medication assignment in adolescents taking imipramine versus placebo in a clinical trial . METHOD Sixty-three anxious-depressed adolescents in an 8-week double-blind study of imipramine versus placebo , each in combination with cognitive-behavioral therapy for school refusal , were evaluated . Measures of side effects , global improvement , family functioning , medication compliance based on pill counts , and guesses of drug assignment ( imipramine versus placebo ) were analyzed . RESULTS Mean side effects ratings were significantly higher for the imipramine group compared with the placebo group ( p = .001 ) . Side effects were not associated with noncompliance or with dropping out . Oppositional defiant disorder ( ODD ) in the adolescents was significantly associated with medication noncompliance ( p = .036 ) . On the Family Adaptability and Cohesion Evaluation Scale II ( FACES II ) , low family adaptability ( i.e. , rigidity ) , low family cohesion ( i.e. , disengagement ) , and extreme family type were significantly associated with greater noncompliance with medications . Accuracy rates for guessing medication assignment ( imipramine versus placebo ) were 66 % for subjects , 62.5 % for mothers , and 79.5 % for the psychiatrist . Logistic regression demonstrated that side effects ( p = .005 ) and global improvement scores ( p = .06 ) predicted the psychiatrist 's guesses of drug assignment . CONCLUSIONS Side effects were not associated with noncompliance . Nonadherence with taking medications was associated with ODD in the adolescents and problematic family functioning on FACES II . The psychiatrist , who was blind to treatment condition , guessed the subjects ' medication assignments with high accuracy . Thus , because of expectancy bias , the data support the use of blind independent evaluators for rating changes in medication trials OBJECTIVE Escitalopram is a selective serotonin reuptake inhibitor antidepressant indicated for use in adults . This trial examined the efficacy and safety of escitalopram in pediatric depression . METHOD Patients ( 6 - 17 years old ) with major depressive disorder were r and omized to receive 8 weeks of double-blind flexibly dosed treatment with escitalopram ( 10 - 20 mg/day ; n = 131 ) or placebo ( n = 133 ) . R and omization was not stratified by age . The primary efficacy measure was the mean change from baseline to endpoint in Children 's Depression Rating Scale-Revised ( CDRS-R ) scores , using the last observation carried forward approach . RESULTS A total of 82 % of patients completed treatment . Escitalopram did not significantly improve CDRS-R scores compared to placebo at endpoint ( least squares mean difference = -1.7 , p = .31 ; last observation carried forward ) . In a post hoc analysis of adolescent ( ages 12 - 17 years ) completers , escitalopram significantly improved CDRS-R scores compared with placebo ( least squares mean difference = -4.6 , p = .047 ) . Headache and abdominal pain were the only adverse events in > 10 % of patients in the escitalopram group . Discontinuation rates caused by adverse events were 1.5 % for both groups . Potential suicide-related events were observed in one escitalopram- and two placebo-treated patients . There were no completed suicides . CONCLUSIONS Although there were no significant differences between escitalopram and placebo in the total population , the data suggest that escitalopram may have beneficial effects in adolescent patients . Escitalopram appeared to be well tolerated Background A mood-related ruminative response style increases the risk of onset and persistence of depression . This preliminary study investigated whether , in depressed adolescents , cognitive-behaviour therapy reduces mood-related ruminative response style . Whether specific factors within the rumination scale were differentially affected by CBT is also reported . Methods 26 depressed adolescents were r and omised to receiving serotonin-specific reuptake inhibitor antidepressants ( SSRI ) plus psychosocial treatment as usual or SSRI and psychosocial treatment as usual plus CBT . Ruminative response style and depressive symptoms were measured at baseline and after 30 weeks of treatment , with the Responses to Depression Question naire and Mood and Feelings Question naire . Results There were significantly greater reductions in ruminations in the CBT group compared to the non-CBT group ( p = .002 ) . There was no significant difference in the reduction in self-reported depressive symptoms between the groups . Rumination was reduced to levels of never-depressed controls in adolescents who had recovered from depression and received CBT . There were greater falls in the CBT group in the more pathological ' brooding ' factor of rumination . Conclusion These findings suggest that adding CBT to SSRI medication in the presence of active clinical care causes a greater reduction in mood-related ruminative response style in depressed adolescents . This may reduce the risk of future relapse . Trial registration Current Controlled Trials ISRCNT83809224 OBJECTIVE The aim of this study was to compare fluoxetine dosage titration to 40 - 60 mg/day with fixed fluoxetine 20-mg/day treatment for an additional 10 weeks in pediatric out patients with major depressive disorder ( MDD ) who had not met protocol -defined response criteria after 9-week acute fluoxetine treatment . METHODS Patients unresponsive ( less than or equal to 30 % decrease in Children 's Depression Rating Scale-Revised [ CDRS-R ] score ) after 9-week fluoxetine treatment were r and omly reassigned to continue at 20 mg/day or to increase to 40 mg/day . After 4 weeks , patients unresponsive to 40 mg/day could receive 60 mg/day . RESULTS Twenty-nine ( 29 ) patients , 9 - 17 years of age , received fluoxetine 40 - 60 mg/day ( n = 14 ) or 20 mg/day ( n = 15 ) . At the conclusion of this study phase , 10 patients ( 71 % ) on 40 - 60 mg/day met the response criteria , versus 5 patients ( 36 % ) on 20 mg/day ( p = 0.128 ) . Mean CDRS-R scores improved in both treatment groups ( fluoxetine 40 - 60 mg/day , -9.4 ; fluoxetine 20 mg/day , -1.5 ; p = 0.099 ) . Adverse events were similar in both groups . However , this study phase was statistically underpowered for detecting differences between treatment groups . CONCLUSION More than two thirds of patients whose dosage was increased responded within 10 weeks , suggesting dose escalation may benefit some patients . Approximately one third of patients unresponsive to initial treatment with fluoxetine 20 mg responded to this fixed dosage within another 10 weeks . Fluoxetine 20 - 60 mg/day was well tolerated OBJECTIVE To assess the efficacy and tolerability of paroxetine in pediatric major depressive disorder . METHOD Subjects 7 to 17 years old with major depressive disorder received paroxetine ( 10 - 50 mg/day ) or placebo for 8 weeks from 2000 to 2001 . The primary efficacy measure was change from baseline in the Children 's Depression Rating Scale-Revised total score at week 8 last observation carried forward ) . Safety was primarily assessed by spontaneous reporting of adverse events . RESULTS A total of 206 patients ( intent to treat ) were r and omized to paroxetine ( n = 104 ) or placebo ( n = 102 ) . Week 8 Children 's Depression Rating Scale-Revised total score adjusted mean changes from baseline for patients receiving paroxetine and placebo were -22.58 ( SE 1.47 ) and -23.38 points ( SE 1.60 ) , respectively ( 0.80 , 95 % confidence interval -3.09 to 4.69 , p = 0.684 ) . Increased cough ( 5.9 % versus 2.9 % ) , dyspepsia ( 5.9 % versus 2.9 % ) , vomiting ( 5.9 % versus 2.0 % ) , and dizziness ( 5.0 % versus 1.0 % ) occurred in > or=5 % of the paroxetine group and at least twice that of the placebo group . Six of 104 ( 5.8 % ) paroxetine patients reported serious adverse events compared to 1 placebo patient ( 1.0 % ) . The incidence of adverse events of suicidal behavior and /or ideation while taking study medication ( excluding taper ) was 1.92 % ( 2/104 ) for paroxetine versus 0.98 % ( 1/102 ) for placebo . CONCLUSIONS Paroxetine was not shown to be more efficacious than placebo for treating pediatric major depressive disorder OBJECTIVE To determine the efficacy and tolerability of the tricyclic antidepressant desipramine ( DMI ) in the treatment of DSM-III-R-diagnosed major depressive disorder in adolescents . METHOD Sixty adolescents ( 42 female , 18 male ; aged 15 to 19 years ) diagnosed with major depressive disorder using clinical interview and Schedule for Affective Disorders and Schizophrenia for School-Age Children were r and omized to receive either DMI ( 200 mg daily in divided doses ) or placebo for six consecutive weeks following a 1-week placebo period . Treatment outcome was determined using the Hamilton Depression Rating Scale and the Beck Depression Inventory . Tolerability was determined using a symptom side effects scale . In addition , a variety of laboratory and cardiovascular monitoring was performed . RESULTS No significant differences in treatment outcome between DMI- and placebo-treated groups were determined . Neither DMI , nor its metabolite 2-hydroxy-DMI , nor their ratio , was positively correlated to treatment outcome . The DMI group endorsed more side effects but there were no significant between-group differences in any laboratory , electrocardiographic , or other cardiovascular parameters apart from heart rate , which was increased in the DMI-treated group ( p = .03 ) . CONCLUSIONS Given the findings of this study and our review of previously published reports of tricyclic antidepressant treatment in this population , the routine use of short-term ( 6 weeks ) DMI in the treatment of adolescent depression is not supported by the data on h and . Further investigations into what constitutes optimal psychopharmacological treatment of adolescent depression are warranted Major depressive disorder is a highly prevalent and debilitating condition in youth , so developing efficient treatments is a priority for mental health professionals . Psychotherapy ( i.e. , cognitive behavioral therapy/CBT ) , pharmacotherapy ( i.e. , SSRI medication ) , and their combination have been shown to be effective in treating youth depression ; however , the results are still mixed and there are few studies engaging multi-level analyses ( i.e. , subjective , cognitive , and biological ) . Therefore , the aims of this r and omized control study ( RCT ) were both theoretical - integrating psychological and biological markers of depression in a multi-level outcome analysis - and practical - testing the generalizability of previous results on depressed Romanian youth population . Eighty-eight ( N=88 ) depressed Romanian youths were r and omly allocated to one of the three treatment arms : group Rational Emotive Behavior Therapy (REBT)/CBT ( i.e. , a form of CBT ) , pharmacotherapy ( i.e. , sertraline ) , and group REBT/CBT plus pharmacotherapy . The results showed that all outcomes ( i.e. , subjective , cognitive , and biological ) significantly change from pre to post-treatment under all treatment conditions at a similar rate and there were no significant differences among conditions at post-test . In case of categorical analysis of the clinical response rate , we found a non-significant trend favoring group REBT/CBT therapy . Results of analyses concerning outcome interrelations are discussed CONTEXT The efficacy , safety , and tolerability of selective serotonin reuptake inhibitors ( SSRIs ) in the treatment of adults with major depressive disorder ( MDD ) are well established . Comparatively few data are available on the effects of SSRIs in depressed children and adolescents . OBJECTIVE To evaluate the efficacy and safety of sertraline compared with placebo in treatment of pediatric patients with MDD . DESIGN AND SETTING Two multicenter r and omized , double-blind , placebo-controlled trials were conducted at 53 hospital , general practice , and academic centers in the United States , India , Canada , Costa Rica , and Mexico between December 1999 and May 2001 and were pooled a priori . PARTICIPANTS Three hundred seventy-six children and adolescents aged 6 to 17 years with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition-defined MDD of at least moderate severity . INTERVENTION Patients were r and omly assigned to receive a flexible dosage ( 50 - 200 mg/d ) of sertraline ( n = 189 ) or matching placebo tablets ( n = 187 ) for 10 weeks . MAIN OUTCOME MEASURES Change from baseline in the Children 's Depression Rating Scale-Revised ( CDRS-R ) Best Description of Child total score and reported adverse events . RESULTS Sertraline-treated patients experienced statistically significantly greater improvement than placebo patients on the CDRS-R total score ( mean change at week 10 , -30.24 vs -25.83 , respectively ; P = .001 ; overall mean change , -22.84 vs -20.19 , respectively ; P = .007 ) . Based on a 40 % decrease in the adjusted CDRS-R total score at study end point , 69 % of sertraline-treated patients compared with 59 % of placebo patients were considered responders ( P = .05 ) . Sertraline treatment was generally well tolerated . Seventeen sertraline-treated patients ( 9 % ) and 5 placebo patients ( 3 % ) prematurely discontinued the study because of adverse events . Adverse events that occurred in at least 5 % of sertraline-treated patients and with an incidence of at least twice that in placebo patients included diarrhea , vomiting , anorexia , and agitation . CONCLUSION The results of this pooled analysis demonstrate that sertraline is an effective and well-tolerated short-term treatment for children and adolescents with MDD OBJECTIVE To test a collaborative-care , cognitive-behavioral therapy ( CBT ) program adjunctive to selective serotonin reuptake inhibitor ( SSRI ) treatment in HMO pediatric primary care . METHOD A r and omized effectiveness trial comparing a treatment-as-usual ( TAU ) control condition consisting primarily of SSRI medication delivered outside the experimental protocol ( n = 75 ) versus TAU SSRI plus brief CBT ( n = 77 ) . Participants were identified by a recent dispense of SSRI medication followed by telephone screening . Adolescents with a diagnosis of major depressive disorder ( n = 152 ) were enrolled . The CBT program employed cognitive restructuring and /or behavioral activation training . Therapists consulted with prescribing pediatricians to improve medication adherence . RESULTS Through 1-year follow-up , the authors found CBT advantages on the Short Form-12 Mental Component Scale ( p = .04 ) , reductions in TAU outpatient visits ( p = .02 ) , and days ' supply of all medications ( p = .01 ) . No effects were detected for major depressive disorder episodes ; a nonsignificant trend favoring CBT was detected on the Center for Epidemiology Depression Scale ( p = .07 ) . CONCLUSIONS The authors detected a weak CBT effect , possibly rendered less significant by the small sample and likely attenuated by the unexpected reduction in SSRI pharmacotherapy in the CBT condition . Small , incremental improvements over monotherapy , such as observed in this study , most likely represent the new norm in adolescent depression treatment research Eighty-seven moderately to severely depressed psychiatric out patients were r and omly assigned to 12 weeks of cognitive therapy ( n = 24 ) , pharmacotherapy ( n = 24 ) , cognitive therapy plus pharmacotherapy ( n = 22 ) or cognitive therapy plus active placebo ( n = 17 ) . Seventy patients completed the treatment protocol ; 17 dropped out before the end of the treatment period . Completers and dropouts did not differ at pretreatment on demographic variables , measures of depression , cognitive functioning or social adjustment . Sixteen of the 17 patients who dropped out were followed up and interviewed to assess their clinical status and reasons for discontinuing treatment . Neither group remained depressed at follow-up . Practical matters and issues related to the type of treatment received seemed to contribute most to patients ' decision to drop out . Patients assigned to the combination therapies were more likely to complete the research protocol than those assigned to single treatment modalities . These findings are discussed in terms of their implication s for clinical practice and outcome research CONTEXT The Treatment for Adolescents With Depression Study evaluates the effectiveness of fluoxetine hydrochloride therapy , cognitive behavior therapy ( CBT ) , and their combination in adolescents with major depressive disorder . OBJECTIVE To report effectiveness outcomes across 36 weeks of r and omized treatment . DESIGN AND SETTING R and omized , controlled trial conducted in 13 academic and community sites in the United States . Cognitive behavior and combination therapies were not masked , whereas administration of placebo and fluoxetine was double-blind through 12 weeks , after which treatments were unblinded . Patients assigned to placebo were treated openly after week 12 , and the placebo group is not included in these analyses by design . PARTICIPANTS Three hundred twenty-seven patients aged 12 to 17 years with a primary DSM-IV diagnosis of major depressive disorder . INTERVENTIONS All treatments were administered per protocol . MAIN OUTCOME MEASURES The primary dependent measures rated blind to treatment status by an independent evaluator were the Children 's Depression Rating Scale-Revised total score and the response rate , defined as a Clinical Global Impressions-Improvement score of much or very much improved . RESULTS Intention-to-treat analyses on the Children 's Depression Rating Scale-Revised identified a significant time x treatment interaction ( P < .001 ) . Rates of response were 73 % for combination therapy , 62 % for fluoxetine therapy , and 48 % for CBT at week 12 ; 85 % for combination therapy , 69 % for fluoxetine therapy , and 65 % for CBT at week 18 ; and 86 % for combination therapy , 81 % for fluoxetine therapy , and 81 % for CBT at week 36 . Suicidal ideation decreased with treatment , but less so with fluoxetine therapy than with combination therapy or CBT . Suicidal events were more common in patients receiving fluoxetine therapy ( 14.7 % ) than combination therapy ( 8.4 % ) or CBT ( 6.3 % ) . CONCLUSIONS In adolescents with moderate to severe depression , treatment with fluoxetine alone or in combination with CBT accelerates the response . Adding CBT to medication enhances the safety of medication . Taking benefits and harms into account , combined treatment appears superior to either monotherapy as a treatment for major depression in adolescents A sample of 137 child and adolescent out patients with major depressive disorder were examined to identify baseline clinical characteristics that predicted symptom severity at the end of a 3-week evaluation period and to determine whether change in symptom severity between week 1 and week 2 predicted symptom severity at week three . Subjects underwent three consecutive weekly evaluations prior to being considered for entry into a double-blind , placebo-controlled treatment trial of fluoxetine . Results indicated that the combination of age , social functioning , family history , Children 's Depressive Rating Scale-Revised ( CDRS-R ) ( Poznanski et al. ( 1985 ) Psychopharmacol . Bull . 21 , 979 - 989 ) total score at visit one , and percent change in symptom severity between visit one and visit two were predictors of symptom severity at visit three . These findings suggest that ( 1 ) subjects should not be excluded from r and omized controlled clinical treatment trials based solely on improvement of symptom severity between visits and ( 2 ) an extended evaluation period is warranted , especially for adolescents whose symptom severity tends to fluctuate from week to week OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of duloxetine fixed dose in the treatment of children ( 7 - 11 years ) and adolescents ( 12 - 17 years ) with major depressive disorder ( MDD ) . METHODS Patients ( n=463 ) in this 36 week study ( 10 week acute and 26 week extension treatment ) received duloxetine 60 mg QD ( n=108 ) , duloxetine 30 mg QD ( n=116 ) , fluoxetine 20 mg QD ( n=117 , active control ) , or placebo ( n=122 ) . Measures included : Children 's Depression Rating Scale-Revised ( CDRS-R ) , treatment-emergent adverse events ( TEAEs ) , and Columbia-Suicide Severity Rating Scale ( C-SSRS ) . RESULTS Neither active drug ( duloxetine or fluoxetine ) separated significantly ( p<0.05 ) from placebo on mean change from baseline to end-point ( 10 weeks ) on the CDRS-R total score . Total TEAEs and discontinuation for AEs were significantly ( p<0.05 ) higher only for the duloxetine 60 mg group versus the placebo group during acute treatment . No clinical ly significant electrocardiogram ( ECG ) or laboratory abnormalities were observed , and no completed suicides or deaths occurred during the study . A total of 7 ( 6.7 % ) duloxetine 60 mg , 6 ( 5.2 % ) duloxetine 30 mg , 9 ( 8.0 % ) fluoxetine , and 11 ( 9.4 % ) placebo patients had worsening of suicidal ideation from baseline during acute treatment . Of the patients with suicidal ideation at baseline , 13/16 ( 81 % ) duloxetine 60 mg , 16/17 ( 94 % ) duloxetine 30 mg , 11/16 ( 69 % ) fluoxetine , and 13/15 ( 87 % ) placebo had improvement in suicidal ideation at end-point during acute treatment . One fluoxetine , one placebo , and six duloxetine patients had treatment-emergent suicidal behavior during the 36 week study . CONCLUSIONS Trial results were inconclusive , as neither the investigational drug ( duloxetine ) nor the active control ( fluoxetine ) separated from placebo on the CDRS-R at 10 weeks . No new duloxetine safety signals were identified relative to those seen in adults . Clinical Trial Registry Number ( www . Clinical Trials.gov ): NCT00849693 OBJECTIVE Many patients with chronic heart failure ( CHF ) are thought to be non-adherent to their prescribed medications . The objective was to describe perceptions about and adherence to regular medicines and study medication at baseline and study end in CHF patients participating in a clinical trial . METHODS In the carvedilol or metoprolol European trial ( COMET ) , patients ( N = 3029 ) with CHF were r and omised and followed during a 58-month period . Patients at some Swedish centres answered a question naire at baseline and study end concerning their perception of their regular heart medication and study medication . Adherence was established through estimation of drug usage . RESULTS In the Swedish sub- study , 302 patients responded once to the question naire while 107 patients responded both at baseline and at follow-up . At baseline , 94 % of the patients stated that they believed that the study medication would make them feel better and 82 % believed that their regular heart medication would do so . During the study , patients ' belief in their regular cardiac medication significantly increased . Lack of belief in medication at the start of the study was a strong predictor of withdrawal from the trial ( 64 % versus 6.8 % ; p < 0.0001 ) . Those patients with very poor well-being and limited functional ability ( classified as NYHA III-IV ) at baseline significantly ( p = 0.01 ) increased their belief in the regular cardiac medication but not in their study medication . CONCLUSION Belief in medication may be related to how the patient experiences the medication 's impact on functional ability , symptoms and well-being . PRACTICE IMPLICATION S Early identification of patients ' beliefs about medication seem to be an important factor in counselling and information to patients with CHF OBJECTIVE We present results of a feasibility test of a sequential treatment strategy using continuation phase cognitive-behavioral therapy ( CBT ) to prevent relapse in youths with major depressive disorder ( MDD ) who have responded to acute phase pharmacotherapy . METHOD Forty-six youths ( ages 11 - 18 years ) who had responded to 12 weeks of treatment with fluoxetine were r and omized to receive either 6 months of continued antidepressant medication management ( MM ) or antidepressant MM plus relapse prevention CBT ( MM+CBT ) . Primary outcome was time to relapse , defined as a Childhood Depression Rating Scale-Revised score of 40 or higher and 2 weeks of symptom worsening or clinical deterioration warranting alteration of treatment to prevent full relapse . RESULTS Cox proportional hazards regression , adjusting for depression severity at r and omization and for the hazard of relapsing by age across the trial , revealed that participants in the MM treatment group had a significantly greater risk for relapse than those in the MM+CBT treatment group ( hazard ratio = 8.80 ; 95 % confidence interval 1.01 - 76.89 ; chi = 3.86 , p = .049 ) during 6 months of continuation treatment . In addition , patient satisfaction was significantly higher in the MM+CBT group . No differences were found between the two treatment groups on attrition rate , serious adverse events , and overall global functioning . CONCLUSIONS These preliminary results suggest that continuation phase CBT reduces the risk for relapse by eightfold compared with pharmacotherapy responders who received antidepressant medication alone during the 6-month continuation phase Major depression is commonly found in the child and adolescent population . Venlafaxine , a new antidepressant , has been used successfully in adults ; however , its use in children and adolescents has been very limited . This study evaluated the efficacy and side effect profile of venlafaxine in the treatment of depression in children and adolescents . In a double-blind , placebo-controlled , 6-week study , 33 subjects between the ages of 8 and 17 , who met DSM-IV criteria for major depression , were treated with either venlafaxine and therapy or placebo and therapy . Patient progress data were obtained by weekly rating assessment s. Data on side effects were also obtained weekly . The statistical analysis indicated a significant improvement over time , but it could not be attributed to venlafaxine drug therapy . These findings are consistent with other studies where the efficacy of antidepressants in the treatment of major depression in this age population remains unproven . Low dosage and short length of treatment may account for the lack of efficacy . The findings did , however , suggest a low side-effect profile . Further studies are recommended to assess efficacy and to corroborate its safety in children and adolescents OBJECTIVE Several evidence -based treatment guidelines for major depressive disorder ( MDD ) have been published . However , little is known about how recommendations for treatment are adhered to by patients in current usual psychiatric practice . METHOD The Vantaa Depression Study is a prospect i ve , naturalistic cohort study of 269 psychiatric patients with a new episode of DSM-IV MDD who were interviewed with the Schedules for Clinical Assessment in Neuropsychiatry and Structured Clinical Interview for DSM-III-R Personality Disorders between February 1 , 1997 , and May 31 , 1998 , and again at 6 and 18 months . Treatments provided , as well as adherence to and attitudes toward both antidepressants and psychotherapeutic support/psychotherapy , were investigated among the 198 unipolar patients followed for 18 months . RESULTS Most depression patients ( 88 % ) received antidepressants in the early acute phase , but about half ( 49 % ) terminated treatment prematurely . This premature termination was associated with worse outcome of major depressive episodes , and with negative attitudes , mainly explained by fear of dependence on or side effects of antidepressants . Nearly all patients ( 98 % ) received some psychosocial treatment in the acute phase ; about one fifth ( 16 % ) had weekly psychotherapy during the follow-up . About a quarter of patients admitted nonadherence to ongoing treatments . CONCLUSION Problems of psychiatric care seem most related to continuity of treatment . While adequate treatments are provided in the early acute phase , antidepressants are terminated too soon in about half of patients , often following their autonomous decisions . From a secondary and tertiary preventive point of view , improving continuity of treatment would appear a crucial task for improving the outcome of psychiatric patients with MDD Forty patients aged 13 to 18 years participated in a placebo-controlled double-blind study of fluoxetine . Fifteen subjects in each group completed the eight week study . Approximately two-thirds of the patients showed marked or moderate clinical global improvement with both fluoxetine and placebo . Fluoxetine was superior to placebo on all clinical measures except for sleep disorder , but the differences were not statistically significant . Thirty-two of the patients and their parents were interviewed after a mean follow-up interval of 24 months ( range : 8 - 46 months ) . Mean age at follow-up was 18 years ( range : 15 - 22 years ) . Both groups had shown further improvement at follow-up but there were no significant group differences . Independent of the study , 19 patients ( 59 % ) had received intervening treatment following study termination and nine patients ( 28 % ) were still in treatment . Adolescent depression appears to respond to treatment but both mood disturbance and psychosocial adaptation problems persist , requiring active follow-through We performed a r and om assignment , double-blind , placebo-controlled study of nortriptyline ( NT ) in postpubertal 12- to 17-year-olds with Research Diagnostic Criteria ( RDC ) and DSM-III major depressive disorder . The protocol included a 2-week placebo washout phase and an 8-week double-blind , placebo-controlled phase with weekly plasma level monitoring . Active subjects had their plasma level placed at 80 + /- 20 ng/ml by using previously developed tables to determine the starting dose from a plasma level drawn 24 hours after a single dose administered at baseline . The study population was severely depressed and had a chronic , unremitting course prior to study ; a high percentage of family histories with affective disorder , alcoholism , and suicidality ; and a high rate of comorbidity . Of the 52 subjects enrolled , there were 17 placebo washout responders , 4 dropouts , and 31 completers ( 12 active and 19 placebo ) . Only one active subject responded ; therefore , the study was terminated early . The mean NT plasma level was 91.1 ( 18.3 SD ) ng/ml . The two treatment groups had similar post protocol severity ratings . Subjects on active drug did not evidence the anticholinergic side effects reported in adult sample s. The negative outcome in this study is similar to the findings in our previously reported NT study in prepubertal 6- to 12-year-olds BACKGROUND Only a third of patients with depression respond fully to antidepressant medication but little evidence exists regarding the best next-step treatment for those whose symptoms are treatment resistant . The CoBalT trial aim ed to examine the effectiveness of cognitive behavioural therapy ( CBT ) as an adjunct to usual care ( including pharmacotherapy ) for primary care patients with treatment resistant depression compared with usual care alone . METHODS This two parallel-group multicentre r and omised controlled trial recruited 469 patients aged 18 - 75 years with treatment resistant depression ( on antidepressants for ≥6 weeks , Beck depression inventory [ BDI ] score ≥14 and international classification of diseases [ICD]-10 criteria for depression ) from 73 UK general practice s. Participants were r and omised , with a computer generated code ( stratified by centre and minimised according to baseline BDI score , whether the general practice had a counsellor , previous treatment with antidepressants , and duration of present episode of depression ) to one of two groups : usual care or CBT in addition to usual care , and were followed up for 12 months . Because of the nature of the intervention it was not possible to mask participants , general practitioners , CBT therapists , or research ers to the treatment allocation . Analyses were by intention to treat . The primary outcome was response , defined as at least 50 % reduction in depressive symptoms ( BDI score ) at 6 months compared with baseline . This trial is registered , IS RCT N38231611 . FINDINGS Between Nov 4 , 2008 , and Sept 30 , 2010 , we assigned 235 patients to usual care , and 234 to CBT plus usual care . 422 participants ( 90 % ) were followed up at 6 months and 396 ( 84 % ) at 12 months , finishing on Oct 31 , 2011 . 95 participants ( 46 % ) in the intervention group met criteria for response at 6 months compared with 46 ( 22 % ) in the usual care group ( odds ratio 3·26 , 95 % CI 2·10 - 5·06 , p<0·001 ) . INTERPRETATION Before this study , no evidence from large-scale r and omised controlled trials was available for the effectiveness of augmentation of antidepressant medication with CBT as a next-step for patients whose depression has not responded to pharmacotherapy . Our study has provided robust evidence that CBT as an adjunct to usual care that includes antidepressants is an effective treatment , reducing depressive symptoms in this population . FUNDING National Institute for Health Research Health Technology Assessment OBJECTIVE Major depressive disorder in adolescents is characterized as treatment resistant , but a previous open-label trial of pulse intravenous clomipramine demonstrated rapid relief of depressive symptoms . In the present study a single intravenous dose of clomipramine ( 200 mg ) was compared with saline placebo in a r and omized controlled trial for depressed adolescents . The hypothesis was that adolescents who were treated with pulse clomipramine would exhibit lower scores on the Hamilton Depression Rating Scale at endpoint than would adolescents who received saline and that clomipramine would be superior to saline in terms of antidepressant response . METHOD Sixteen nonsuicidal outpatient adolescents ( mean age = 16.2 years , SD = 1.0 ) who met the DSM-III-R criteria for major depression ( score on 21-item Hamilton scale , > or = 18 ) were r and omly assigned to receive either clomipramine ( 200 mg i.v . , N = 8) or saline ( N = 8) . Assessment s of depression severity were completed 36 hours and 6 days thereafter . RESULTS The adolescents who received pulse clomipramine treatment demonstrated significant decreases in Hamilton depression scores from baseline at 6 days but not at 36 hours . A similar decrease from baseline was found in Clinical Global Impression severity at 6 days but not 36 hours . Seven of the clomipramine-treated patients and three of the saline-treated patients had drops of 50 % or more from baseline in Hamilton depression score . CONCLUSIONS Pulse clomipramine ( 200 mg i.v . ) is associated with dramatic reduction in depressive symptoms at day 6 after infusion , which is significantly different from the effect of placebo OBJECTIVE Recent acute efficacy trials of antidepressants in youth have suggested that high placebo-response rates in children ( < 12 years of age ) indicate that children may be more responsive to non-specific treatment interventions . Yet , these studies generally have not presented age-specific outcome data . The objective of this study was to compare the efficacy outcomes for children ( < 12 years of age ) and adolescents ( > or = 12 years of age ) using the combined data from two previously published double-blind , placebo-controlled trials of fluoxetine . METHODS Children ( < 12 years of age ) and adolescents ( > or = 12 years of age ) with major depressive disorder were r and omized to fluoxetine or placebo for 8 - 9 weeks of treatment . Outcome was assessed using the Children 's Depression Rating Scale-Revised ( CDRS-R ) and Clinical Global Impressions scale . RESULTS R and om regression of the CDRS-R showed a treatment group by age group interaction ( F(1,338)=4.10 , P=.044 ) , indicating that the treatment effect was significantly more pronounced in children than adolescents . Within children , response at exit to fluoxetine was significantly better than placebo ( 56.9 % vs 33.3 % ; P=.009 ) . Adolescent response rates at exit were not significantly different between the groups ( 51.1 % vs 38.6 % ; P=.128 ) . Remission rates were low for both groups . CONCLUSION In the combined fluoxetine trials , drug-placebo difference was greater in children compared with adolescents . Contrary to expectations , the placebo-response rate was lower in the children than the adolescents OBJECTIVE The aim of this study was to examine the impact of co-morbid illnesses on treatment outcomes in depressed children and adolescents aged 7 - 17 who were treated with fluoxetine . METHOD This data set was drawn from two large clinical trials involving children and adolescents with depression . Subjects with a diagnosis of major depressive disorder and depressive symptoms of at least moderate severity as defined by a Children 's Depression Rating Score , Revised ( CDRS-R ) total score > or=40 and a Clinical Global Impressions-Severity ( CGI-S ) rating > or=4 were included . Subjects were r and omized to receive fluoxetine or placebo over an 8-week period . Predictor analyses examining two primary outcomes were conducted : ( 1 ) Response based on Clinical Global Impressions-Improvement ( CGI-I ) score of 1 or 2 , and ( 2 ) remission based on CDRS-R score of < or=28 . Logistic regression models were run to assess whether anxiety disorders were a predictor of response or remission . RESULT A total of 309 study participants were included . The only factor found to influence response was treatment with fluoxetine ( p = 0.022 , odds ratio [ OR ] = 2.08 , 95 % confidence interval [ CI ] 1.30 , 3.31 ) . Several factors were found to influence remission : Treatment with fluoxetine ( p < 0.0001 , OR = 3.17 , 95 % CI 1.80 , 5.57 ) , gender ( p = 0.024 , OR = 1.90 , 95 % CI 1.09 , 3.30 ) , and number of co-morbid diagnoses ( p = 0.026 , OR 0.73 , 95 % CI 0.55 , 0.96 ) . CONCLUSION Anxiety disorders alone did not predict response or remission , but the total number of co-morbid illnesses was associated with remission in depressed children and adolescents treated with fluoxetine BACKGROUND Depression is a major cause of morbidity and mortality in children and adolescents . To date , r and omized , controlled , double-blind trials of antidepressants ( largely tricyclic agents ) have yet to reveal that any antidepressant is more effective than placebo . This article is of a r and omized , double-blind , placebo-controlled trial of fluoxetine in children and adolescents with depression . METHODS Ninety-six child and adolescent out patients ( aged 7 - 17 years ) with nonpsychotic major depressive disorder were r and omized ( stratified for age and sex ) to 20 mg of fluoxetine or placebo and seen weekly for 8 consecutive weeks . R and omization was preceded by 3 evaluation visits that included structured diagnostic interviews during 2 weeks , followed 1 week later by a 1-week , single-blind placebo run-in . Primary outcome measurements were the global improvement of the Clinical Global Impressions scale and the Children 's Depression Rating Scale -- Revised , a measure of the severity depressive symptoms . RESULTS Of the 96 patients , 48 were r and omized to fluoxetine treatment and 48 to placebo . Using the intent to treat sample , 27 ( 56 % ) of those receiving fluoxetine and 16 ( 33 % ) receiving placebo were rated " much " or " very much " improved on the Clinical Global Impressions scale at study exit ( chi 2 = 5.1 , df = 1 , P = .02 ) . Significant differences were also noted in weekly ratings of the Children 's Depression Rating Scale -- Revised after 5 weeks of treatment ( using last observation carried forward ) . Equivalent response rates were found for patients aged 12 years and younger ( n = 48 ) and those aged 13 years and older ( n = 48 ) . However , complete symptom remission ( Children 's Depression Rating Scale -- Revised < or = 28 ) occurred in only 31 % of the fluoxetine-treated patients and 23 % of the placebo patients . CONCLUSION Fluoxetine was superior to placebo in the acute phase treatment of major depressive disorder in child and adolescent out patients with severe , persistent depression . Complete remission of symptoms was rare BACKGROUND In 2001 , the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments ( CANMAT ) partnered to produce evidence -based clinical guidelines for the treatment of depressive disorders . A revision of these guidelines was undertaken by CANMAT in 2008 - 2009 to reflect advances in the field . This article , one of five in the series , review s new studies of psychotherapy in the acute and maintenance phase of MDD , including computer-based and telephone-delivered psychotherapy . METHODS The CANMAT guidelines are based on a question -answer format to enhance accessibility to clinicians . Evidence -based responses are based on up date d systematic review s of the literature and recommendations are grade d according to the Level of Evidence , using pre-defined criteria . Lines of Treatment are identified based on criteria that included evidence and expert clinical support . RESULTS Cognitive-Behavioural Therapy ( CBT ) and Interpersonal Therapy ( IPT ) continue to have the most evidence for efficacy , both in acute and maintenance phases of MDD , and have been studied in combination with antidepressants . CBT is well studied in conjunction with computer-delivered methods and bibliotherapy . Behavioural Activation and Cognitive-Behavioural Analysis System of Psychotherapy have significant evidence , but need replication . Newer psychotherapies including Acceptance and Commitment Therapy , Motivational Interviewing , and Mindfulness-Based Cognitive Therapy do not yet have significant evidence as acute treatments ; nor does psychodynamic therapy . LIMITATIONS Although many forms of psychotherapy have been studied , relatively few types have been evaluated for MDD in r and omized controlled trials . Evidence about the combination of different types of psychotherapy and antidepressant medication is also limited despite widespread use of these therapies concomitantly . CONCLUSIONS CBT and IPT are the only first-line treatment recommendations for acute MDD and remain highly recommended for maintenance . Both computer-based and telephone-delivered psychotherapy -- primarily studied with CBT and IPT -- are useful second-line recommendations . Where feasible , combined antidepressant and CBT or IPT are recommended as first-line treatments for acute MDD OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of duloxetine flexible dose in children ( 7 - 11 years ) and adolescents ( 12 - 17 years ) with major depressive disorder ( MDD ) . METHODS Patients ( n=337 ) in this 36 week study ( 10 week acute and 26 week extension treatment ) received duloxetine ( 60 - 120 mg once daily [ QD ] , n=117 ) , fluoxetine ( 20 - 40 mg QD , n=117 ) , or placebo ( n=103 ) . Measures included : Children 's Depression Rating Scale-Revised ( CDRS-R ) , treatment-emergent adverse events ( TEAEs ) , and Columbia-Suicide Severity Rating Scale ( C-SSRS ) . RESULTS Neither active drug ( duloxetine or fluoxetine ) separated significantly ( p<0.05 ) from placebo on mean change from baseline to end-point ( 10 weeks ) on the CDRS-R total score . There were no significant differences between the duloxetine or fluoxetine groups compared with placebo on serious AEs ( SAEs ) , total TEAEs , or discontinuation for AE during acute treatment . There were no completed suicides or deaths , and no clinical ly significant electrocardiogram ( ECG ) abnormalities observed during the study . One fluoxetine and one duloxetine patient experienced alanine aminotransferase ( ALT ) three or more times the upper limit of normal , which resolved during the study . A total of 8 ( 7.1 % ) duloxetine patients , 7 ( 6.8 % ) placebo patients , and 9 ( 8.0 % ) fluoxetine patients had worsening of suicidal ideation from baseline during acute treatment . Of the patients with suicidal ideation at baseline , 15/19 ( 79 % ) duloxetine , 19/19 ( 100 % ) placebo , and 16/19 ( 84 % ) fluoxetine had improvement in suicidal ideation at end-point during acute treatment . One duloxetine and two fluoxetine patients had treatment-emergent suicidal behavior during the 36 week study . CONCLUSION Trial results were inconclusive , as neither the investigational drug ( duloxetine ) nor the active control ( fluoxetine ) separated from placebo on the CDRS-R at 10 weeks . No new duloxetine safety signals were identified relative to those seen in adults . Clinical Trial Registry Number : NCT00849901 OBJECTIVE The aim of this study was to assess the long-term safety , tolerability , and efficacy of sertraline 50 - 200 mg once-daily in children ( 6 - 11 year olds ) and adolescents ( 12 - 18 year olds ) with a Diagnostic and Statistical Manual of Mental Disorders , 4th edition ( DSM-IV ) diagnosis of major depressive disorder ( MDD ) . METHODS This study consisted of a 24-week open-label observational study of children and adolescents who had completed either of two 10-week double-blind , placebo-controlled trials . The Children 's Depression Rating Scale-Revised ( CDRS-R ) was the primary measure of efficacy . RESULTS Two hundred ninety nine ( 299 ) patients completed the acute studies and were eligible for the extension study . Of these , 226 enrolled , but 5 did not receive treatment . Of 221 patients ( 107 children and 114 adolescents ) , 62.4 % completed the study . The endpoint mean daily dose was 109.9 mg/day . The mean decrease in CDRS-R score from double-blind baseline was 34.8 points ( p < 0.001 ) , with patients showing continued improvement in CDRS-R scores regardless of which treatment they received in the double-blind studies . At endpoint , 86 % of patients met CDRS-R responder and 58 % CDRS-R remitter criteria . CONCLUSIONS Sertraline appears to be well tolerated and safe over 24 weeks of treatment in children and adolescents with MDD . Children and adolescents treated with sertraline appear to have increased improvement over that seen in the first 10 weeks of treatment . These findings need confirmation in placebo-controlled studies OBJECTIVE To evaluate cognitive-behavioral therapy , antidepressant medication alone , and combined CBT and antidepressant medication in the treatment of depressive disorders in adolescents . METHOD Seventy-three adolescents ( ages 12 - 18 years ) with a primary diagnosis of DSM-IV major depressive disorder , dysthymic disorder , or depressive disorder not otherwise specified were r and omly allocated to one of three treatments . Treatment outcome measures were administered before and after acute treatment , and at a 6-month follow-up . Depression diagnosis was the primary outcome measure ; secondary measures were self- and other report and clinician rating of global functioning . The trial was conducted at three community-based clinics between July 2000 and December 2002 . Data analyses used an intent-to-treat strategy . RESULTS Following acute treatment , all treatment groups demonstrated statistically significant improvement on outcome measures ( depressive diagnosis , Reynolds Adolescent Depression Scale , Revised Children 's Manifest Anxiety Scale , Suicidal Ideation Question naire ) , and improvement was maintained at follow-up . Combined cognitive-behavioral therapy and antidepressant medication was not found to be superior to either treatment alone . Compared with antidepressant medication alone , participants receiving cognitive-behavioral therapy alone demonstrated a superior acute treatment response ( odds ratio = 6.86 ; 95 % confidence interval 1.12 - 41.82 ) . Although cognitive-behavioral therapy was found to be superior to antidepressant medication alone for the acute treatment of mild to moderate depression among youth , this may have stemmed from the relatively low dose of sertraline used . CONCLUSIONS All treatments led to a reduction in depression , but the advantages of a combined approach were not evident BACKGROUND This report presents results from the acute treatment phase of a clinical trial design ed to confirm efficacy of a fixed dose of 20 mg of fluoxetine in children and adolescents with major depressive disorder ( MDD ) . METHOD After a 3-week screening period , 122 children and 97 adolescents with MDD ( ) were r and omly assigned to placebo or fluoxetine . After a 1-week placebo lead-in , fluoxetine-treated patients received fluoxetine 10 mg/day for 1 week , then fluoxetine 20 mg/day for 8 weeks . RESULTS Fluoxetine was associated with greater mean improvement in Children 's Depression Rating Scale-Revised ( CDRS-R ) score than placebo after 1 week ( < .05 ) and throughout the study period . Significantly more fluoxetine-treated patients ( 41 % ) met the prospect ively defined criteria for remission than did placebo-treated patients ( 20 % ) ( < .01 ) . More fluoxetine- ( 65 % ) than placebo-treated ( 53 % ) patients met the prospect ively defined response criterion of > or = 30 % decrease in CDRS-R score , but this difference was not significant ( = .093 ) . Significantly more fluoxetine-than placebo-treated patients completed acute treatment ( = .001 ) . There were no significant differences between treatment groups in discontinuations due to adverse events ( = .408 ) . CONCLUSION Fluoxetine 20 mg daily appears to be well tolerated and effective for acute treatment of MDD in child and adolescent out patients . Fluoxetine is the only antidepressant that has demonstrated efficacy in two placebo-controlled , r and omized clinical trials of pediatric depression OBJECTIVE The purpose of this study was to evaluate the extended efficacy , safety , and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder ( MDD ) . METHODS Adolescents ( 12 - 17 years ) who completed an 8-week r and omized , double-blind , flexible-dose , placebo-controlled , lead-in study of escitalopram 10 - 20 mg versus placebo could enroll in a 16 - 24-week , multisite extension trial ; patients maintained the same lead-in r and omization ( escitalopram or placebo ) and dosage ( escitalopram 10 or 20 mg/day , or placebo ) during the extension . The primary efficacy was Children 's Depression Rating Scale-Revised ( CDRS-R ) change from the lead-in study baseline to treatment week 24 ( 8-week lead-in study plus 16-week extension ) ; the secondary efficacy was Clinical Global Impressions-Improvement ( CGI-I ) score at week 24 . All efficacy analyses used the last observation carried forward ( LOCF ) approach ; sensitivity analyses used observed cases ( OC ) and mixed-effects model for repeated measures ( MMRM ) . Safety was evaluated via adverse event ( AE ) reports and the clinician-rated Columbia-Suicide Severity Rating Scale ( C-SSRS ) . RESULTS Following lead-in , 165 patients enrolled in the double-blind extension ( 82 placebo ; 83 escitalopram ) ; 40 ( 48.8 % ) placebo and 37 ( 44.6 % ) escitalopram patients completed treatment . CDRS-R total score improvement was significantly greater for escitalopram than for placebo ( p=0.005 , LOCF ; p=0.014 ; MMRM ) . Response rates ( CDRS-R ≥ 40 % reduction from baseline [ adjusted and unadjusted ] and CGI-I ≤ 2 ) were significantly higher for escitalopram than for placebo ( LOCF ) ; remission rates ( CDRS-R ≤ 28 ) were 50.6 % for escitalopram and 35.7 % for placebo ( p=0.002 ) . OC analyses were not significantly different between groups . The most frequent escitalopram AEs ( ≥ 5 % and more frequent than placebo ) were headache , nausea , insomnia , vomiting , influenza-like symptoms , diarrhea , and urinary tract infection . Most AEs were mild/moderate and not related to the study drug . AEs suggestive of self-harm occurred in 5.7 % and 7.1 % of placebo and escitalopram patients . Occurrence of suicidal behavior and /or suicidal ideation assessed by C-SSRS was 10.9 % ( 14/128 ) for placebo and 14.5 % ( 19/131 ) for escitalopram . CONCLUSIONS Extended use of escitalopram was generally safe and result ed in modest improvement in efficacy in adolescents with MDD OBJECTIVE The aim of this study was to examine the efficacy , safety , and tolerability of paroxetine in adolescents with unipolar major depression . METHOD Two hundred eighty-six ( 286 ) adolescents with unipolar major depression were r and omly assigned to receive either paroxetine or placebo for 12 weeks . RESULTS The proportion of Montgomery-Asberg Depression Rating Scale ( MADRS ) responders ( at least 50 % reduction from baseline ) for paroxetine and placebo were similar and not statistically different at endpoint ( p = 0.702 ) . A similar result was obtained for change from baseline on the Kiddie-Schedule for Affective Disorders and Schizophrenia for School- Age Children ( K-SADS-L ) depression subscale . Among secondary endpoints , only a significantly higher Clinical Global Impression-Improvement ( CGI-I ) response rate was reported in paroxetine-treated patients versus placebo ( 69.2 % versus 57.3 % ; p = 0.045 ) . In general , results differed by age , with patients older than 16 years demonstrating a greater response to active treatment . This age group also reported more adverse experiences ( AEs ) relative to placebo than younger adolescents . Overall , paroxetine was generally well tolerated ( 11 % discontinued owing to an AE versus 7 % of placebo-treated patients ) . A post hoc analysis of AEs related to suicidal behavior suggested a greater incidence of these events for paroxetine than for placebo ( 4.4 % versus 2.1 % ) ; however , this difference was not statistically significant ( odds ratio , 2.15 , 95 % Confidence Interval 0.45 , 10.33 ; p = 0.502 ) . CONCLUSIONS No statistically significant differences were observed for paroxetine compared with placebo on the two prospect ively defined primary efficacy variables . Paroxetine at 20 - 40 mg/day administered over a period of up to 12 weeks was generally well tolerated OBJECTIVE To evaluate the effect of fluoxetine hydrochloride vs placebo on major depressive disorder , substance use disorder ( SUD ) , and conduct disorder ( CD ) in adolescents receiving cognitive behavioral therapy ( CBT ) for SUD . DESIGN R and omized controlled trial . SETTING A single-site study conducted between May 2001 and August 2004 . PARTICIPANTS One hundred twenty-six adolescents aged 13 to 19 years recruited from the community and meeting Diagnostic and Statistical Manual of Mental Disorders ( Fourth Edition ) diagnostic criteria for current major depressive disorder , lifetime CD , and at least 1 nontobacco SUD . INTERVENTIONS Sixteen weeks of fluoxetine hydrochloride , 20 mg/d , or placebo , with CBT . MAIN OUTCOME MEASURES For depression , Childhood Depression Rating Scale-Revised and Clinical Global Impression Improvement ; for SUD , self-reported nontobacco substance use and urine substance use screen results in the past 30 days ; and for CD , self-reported symptoms in the past 30 days . RESULTS Fluoxetine combined with CBT had greater efficacy than did placebo and CBT according to changes on the Childhood Depression Rating Scale-Revised ( effect size , 0.78 ) but not on the Clinical Global Impression Improvement treatment response ( 76 % and 67 % , respectively ; relative risk , 1.08 ) . There was an overall decrease in self-reported substance use ( 4.31 days ; 95 % confidence interval , 2.12 - 6.50 ) and CD symptoms ( relative risk , 1.20 ; 95 % confidence interval , 0.82 - 1.59 ) , but neither difference between groups was statistically significant . The proportion of substance-free weekly urine screen results was higher in the placebo-CBT group than in the fluoxetine-CBT group ( mean difference , 2.10 ; 95 % confidence interval , 0.37 - 4.15 ) . CONCLUSIONS Fluoxetine and CBT had greater efficacy than did placebo and CBT on one but not both depression measures and was not associated with greater decline in self-reported substance use or CD symptoms . The CBT may have contributed to higher-than-expected treatment response and mixed efficacy findings , despite its focus on SUD OBJECTIVE Although recent studies and meta-analyses confirm the efficacy of antidepressants in the acute phase of treatment for adolescent depression , there are few data available to allow assessment of the value of continued use of antidepressants in depressed adolescents after acute response . This study examines the benefit of maintenance treatment with sertraline in adolescents aged 13 - 19 years with major depression using a multi-site r and omized placebo controlled discontinuation design . METHODS Subjects with a diagnosis of depression who responded to open-label treatment with sertraline in a 12-week acute phase and did not relapse with open-label continuation treatment for 24 weeks were r and omized to placebo or continued treatment with sertraline for 52 weeks . RESULTS Twenty-two subjects were r and omized to maintenance treatment with sertraline ( n = 13 ) versus placebo ( n = 9 ) . A higher proportion of subjects treated with sertraline ( 38 % ) remained well as compared to those on placebo ( 0 % ) . Survival analyses found no significant differences between the groups ( p = 0.17 ) . CONCLUSIONS This is the first study to examine the outcome to maintenance treatment for adolescents with major depression . Although the sample size was small , the findings suggest a possible benefit of maintenance treatment with sertraline over placebo . A larger clinical trial with adequate power is required to confirm or disconfirm these findings The study was design ed to test the efficacy of desipramine in adolescents with major depression ( MDD ) . In addition , we assessed the presence of atypical features of MDD , consisting of mood reactivity and two of four associated features ( rejection sensitivity , hyperphagia , hypersomnia , and leaden paralysis ) . Patients were r and omized to desipramine ( DMI ) or placebo for 6 weeks , provided they failed to improve ( e.g. , meeting MDD criteria and a Hamilton Depression Scale score ≥18 ) after 2 weeks on single blind placebo . Of 94 adolescents ( ages 13–18 ) who were diagnosed as having MDD , 64 entered the study and 62 received placebo for 2 weeks . Of these , 45 were r and omized to DMI or placebo . Completer analyses did not reveal significant improvement for the active treatment compared to the placebo . A large proportion of adolescents responded to placebo ( 50 % ) , suggesting the need for very large sample s to detect differential treatment efficacy , should it exist . A relatively high rate of atypical depression was observed ( 47 % in the 64 patients entered ) . In view of the demonstrated specificity of monoamine oxidase inhibitor efficacy in adults with atypical features of MDD , this clinical subtype may have relevance to future investigation of therapeutic interventions in adolescent MDD . Depression and Anxiety 7:15–31 , 1998 . © 1998 Wiley‐Liss , OBJECTIVE To assess the response to a serotonergic/noradrenergic tricyclic antidepressant , amitriptyline ( AMI ) , in a group of adolescents with treatment-resistant major depressive disorder ( MDD ) . METHOD Twenty-seven depressed adolescents admitted to a state hospital underwent a 10-week r and omized , controlled trial with a flexible dose of AMI or placebo . RESULTS There were no differences between patients taking AMI ( n = 13 ) and placebo ( n = 14 ) . Both treatment groups showed approximately 70 % to 80 % improvement on the clinical outcome measurements , and 65 % to 70 % showed functional improvement . At the end of the protocol , 30 % of patients still fulfilled criteria for MDD and had impaired functioning . Patients taking AMI experienced significantly more dry mouth and tachycardia . The final AMI dose was 173.1 mg/day + /- 56.3 mg/day ; blood levels were 226.2 ng/mL + /- 80.8 ng/mL. CONCLUSIONS No significant differences were found between AMI and placebo , in part because of the high placebo response rate . Although both treatment groups showed substantial response , at the end of treatment a substantial proportion of patients still had MDD of subsyndromal symptoms of depression . This and other studies of tricyclic antidepressants question the use of this medication as first-line treatment for youths with MDD BACKGROUND Major depression is an important and costly problem among adolescents , yet evidence to support the provision of cost-effective treatments is lacking . AIMS To assess the short-term cost-effectiveness of combined selective serotonin reuptake inhibitors ( SSRIs ) and cognitive-behavioural therapy ( CBT ) together with clinical care compared with SSRIs and clinical care alone in adolescents with major depression . METHOD Pragmatic r and omised controlled trial in the UK . Outcomes and costs were assessed at baseline , 12 and 28 weeks . RESULTS The trial comprised 208 adolescents , aged 11 - 17 years , with major or probable major depression who had not responded to a brief initial psychosocial intervention . There were no significant differences in outcome between the groups with and without CBT . Costs were higher in the group with CBT , although not significantly so ( P=0.057 ) . Cost-effectiveness analysis and exploration of the associated uncertainty suggest there is less than a 30 % probability that CBT plus SSRIs is more cost-effective than SSRIs alone . CONCLUSIONS A combination of CBT plus SSRIs is not more cost-effective in the short-term than SSRIs alone for treating adolescents with major depression in receipt of routine specialist clinical care |
2,299 | 22,189,484 | The ACEI/ARB benefit over placebo was significant for all outcomes except microalbuminuria .
A network meta- analysis detected significant treatment effects across all outcomes for both active drugs and placebo comparisons .
Conclusions /interpretationOur review suggests a consistent reno-protective effect of ACEI/ARB over other antihypertensive drugs , mainly CCBs , and placebo in type 2 diabetes .
The lack of any differences in BP decrease between ACEI/ARB and active comparators suggest this benefit is not due simply to the antihypertensive effect | Aims /hypothesisThis meta- analysis aim ed to compare the renal outcomes between ACE inhibitor (ACEI)/angiotensin II receptor blocker ( ARB ) and other antihypertensive drugs or placebo in type 2 diabetes . | BACKGROUND Diabetes mellitus is a strong risk factor for cardiovascular and renal disease . We investigated whether the angiotensin-converting-enzyme ( ACE ) inhibitor ramipril can lower these risks in patients with diabetes . METHODS 3577 people with diabetes included in the Heart Outcomes Prevention Evaluation study , aged 55 years or older , who had a previous cardiovascular event or at least one other cardiovascular risk factor , no clinical proteinuria , heart failure , or low ejection fraction , and who were not taking ACE inhibitors , were r and omly assigned ramipril ( 10 mg/day ) or placebo , and vitamin E or placebo , according to a two-by-two factorial design . The combined primary outcome was myocardial infa rct ion , stroke , or cardiovascular death . Overt nephropathy was a main outcome in a sub study . FINDINGS The study was stopped 6 months early ( after 4.5 years ) by the independent data safety and monitoring board because of a consistent benefit of ramipril compared with placebo . Ramipril lowered the risk of the combined primary outcome by 25 % ( 95 % CI 12 - 36 , p=0.0004 ) , myocardial infa rct ion by 22 % ( 6 - 36 ) , stroke by 33 % ( 10 - 50 ) , cardiovascular death by 37 % ( 21 - 51 ) , total mortality by 24 % ( 8 - 37 ) , revascularisation by 17 % ( 2 - 30 ) , and overt nephropathy by 24 % ( 3 - 40 , p=0.027 ) . After adjustment for the changes in systolic ( 2.4 mm Hg ) and diastolic ( 1.0 mm Hg ) blood pressures , ramipril still lowered the risk of the combined primary outcome by 25 % ( 12 - 36 , p=0.0004 ) . INTERPRETATION Ramipril was beneficial for cardiovascular events and overt nephropathy in people with diabetes . The cardiovascular benefit was greater than that attributable to the decrease in blood pressure . This treatment represents a vasculoprotective and renoprotective effect for people with diabetes The primary results of a three-year prospect i ve , double-blind , placebo-controlled trial in non-insulin-dependent diabetic ( NIDDM ) patients show that an anti-hypertensive regimen , which includes the ACE inhibitor enalapril , preserves renal function to a greater extent than therapy with antihypertensive agents excluding ACE inhibitors ( J Am Soc Nephrol 3:335 , 1992 ) . The influence of baseline urinary albumin excretion on the renal protective effects of enalapril treatment in these subjects was the objective of this further analysis . Adequate data were available in 121 patients of the 165 hypertensive NIDDM individuals studied [ baseline glomerular filtration rate ( GFR ) 30 to 100 ml/min/1.73 m2 ] . Twenty-four hour urinary excretion of albumin ( UAE ) , protein , urea nitrogen , creatinine and isotopically determined GFR were measured at baseline and six month intervals . Glycemic control and blood pressure regulation were assessed every three months . The rate of loss of GFR was significantly greater in patients with overt proteinuria at baseline ( UAE > 300 mg/24 hr ) as compared to patients with baseline sub- clinical proteinuria ( UAE < or = 300 mg/24 hr ) . Antihypertensive treatment with enalapril preserved GFR significantly better ( P < 0.01 ) in the patients with sub- clinical proteinuria at baseline ( UAE < or = 300 mg/24 hr ) than other antihypertensive treatments which excluded the ACE inhibitor . Furthermore , only 7 % of the enalapril-treated group progressed to clinical albuminuria compared to 21 % of control treated patients . Although the enalapril-treated group had a lower mean blood pressure during the maintenance period , no correlation between blood pressure ( systolic , diastolic or mean arterial ) and rate of change of GFR was observed . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE Determine the prevalence of microalbuminuria in patients with type 2 diabetes mellitus ( DM ) in general practice , as an independent risk factor for cardiovascular diseases . DESIGN Prospect i ve , descriptive . METHOD Data were collected on patients with type 2 DM in the Zwolle region of the Netherl and s , all of whom were being treated by their general practitioner . The inclusion period was 1 February 2000 - 31 January 2001 . The study formed part of a larger investigation , in which the albumin concentration in a urine sample and the albumin-creatinin ratio were determined once per year . A total of 32 general practitioners took part in the study . RESULTS In the general practice s studied , 2094 patients were known with type 2 DM and 1653 ( 79 % ) were treated exclusively by the general practitioner . Of these 1653 patients , 67 ( 4 % ) were excluded and of the 1586 invited patients remaining , 1441 ( 91 % ) participated . Microalbuminuria was present in 33 % of the patients and macroalbuminuria in 7 % of the patients , and the prevalences increased with age : < 50 , 50 - 70 and > 70 years . 18 % ( 6/33 ) of the patients aged < 50 years with microalbuminuria were treated with an ACE inhibitor or angiotensin II antagonist compared to 33 % ( 183/548 ) of patients > or = 50 years . 91 % ( 488/539 ) of the patients > or = 50 years with microalbuminuria had hypertension and /or lipid profile abnormalities and 82 % ( 402/488 ) of them were not treated or did not receive adequate treatment for this condition . CONCLUSION Microalbuminuria and macroalbuminuria were present in respectively 33 % and 7 % of the patients with type 2 DM in primary care . The treatment of hypertension and lipid profile abnormalities was often inadequate . Therefore , screening patients aged 50 years and older with type 2 DM for albuminuria is justified Background —The aim of this study was to assess the level of urinary albumin excretion ( microalbuminuria ) , which is associated with increased risk of coronary heart disease and death , in the population . Microalbuminuria has been suggested as an atherosclerotic risk factor . However , the lower cutoff level of urinary albumin excretion is unknown . It is also unknown whether impaired renal function confounds the association . Methods and Results —In the Third Copenhagen City Heart Study in 1992 to 1994 , 2762 men and women 30 to 70 years of age underwent a detailed cardiovascular investigation program , including a timed overnight urine sample . The participants were then followed up prospect ively by registers until 1999 with respect to coronary heart disease and until 2001 with respect to death . During follow-up , 109 incident cases of coronary heart disease and 276 deaths were traced . A urinary albumin excretion above the upper quartile , ie , 4.8 μg/min , was associated with increased risk of coronary heart disease ( RR , 2.0 ; 95 % CI , 1.4 to 3.0 ; P < 0.001 ) and death ( RR , 1.9 ; 95 % CI , 1.5 to 2.4 ; P < 0.001 ) independently of age , sex , renal creatinine clearance , diabetes mellitus , hypertension , and plasma lipids . Lower levels of urinary albumin excretion were not associated with increased risk . Conclusions —Microalbuminuria , defined as urinary albumin excretion > 4.8 μg/min ( corresponding to ≈6.4 μg/min during daytime ) , is a strong and independent determinant of coronary heart disease and death . Our suggestion is to redefine microalbuminuria accordingly and perform intervention studies Objective The aim of this open-labelled , r and omised , parallel-group study was to evaluate the effect of long-term monotherapy with manidipine or lisinopril on albumin excretion rate ( AER ) and left ventricular mass index ( LVMI ) in hypertensive patients with type-2 diabetes and microalbuminuria . Methods After a 4-week wash-out period , 174 patients with essential hypertension [ diastolic blood pressure ( DBP ) > 80 mmHg and < 100 mmHg ] , type-2 diabetes and microalbuminuria were r and omised to manidipine 10 mg o.d . or lisinopril 10 mg o.d . ; after 8 weeks , the dose was doubled in non-responders ( DBP > 80 mmHg ) ; after 3 months , treatment was discontinued in the non-responder patients and in those complaining of side effects ; the remaining 121 patients continued their therapy with manidipine or lisinopril , and 99 completed the 2-year study . At the end of the wash-out period , of the titration period and after 6 , 12 , 18 and 24 months of treatment , BP was measured , AER , creatinine clearance , glycosylated haemoglobin ( HbA1c ) and body mass index ( BMI ) were evaluated and an echocardiographic evaluation was performed . Results The 99 patients who completed the study were statistically analysed according to a per- protocol evaluation . Manidipine and lisinopril significantly reduced systolic blood pressure ( SBP ) and DBP levels ( at 24 months , −22.3/15.5 mmHg , P<0.001 versus baseline and −21.4/15.7 mmHg , P<0.01 versus baseline , respectively ) . Both drugs provided a significant decrease in AER , but it was significantly more pronounced with lisinopril ( at 24 weeks , −37.2 mg/24 h , P<0.001 versus baseline ) than with manidipine ( –29.9 mg/24 h , P<0.05 versus baseline ) and became evident earlier in the lisinopril group ( after 3 months versus 6 months of treatment ) . Manidipine produced a greater reduction of LVMI than lisinopril ( −14.9 g/m2 versus –10.8 g/m2 at 24 months ) . The effect was more pronounced in patients with left ventricular hypertrophy at baseline ( −19.8 g/m2 versus –12.8 g/m2 , P<0.05 ) . Conclusion These data suggest that , despite similar BP lowering , non-haemodynamic factors play an important role in the pharmacological reduction of AER and LVMI in diabetic hypertensive patients The aim of this study was to compare the effects of ramipril and nitrendipine chronic treatment on urinary albumin excretion ( UAE ) in hypertensive patients with type II non-insulin-dependent diabetes mellitus ( NIDDM ) and impaired renal function . A 2-year , prospect i ve , r and omised study was conducted on 51 men with a diastolic blood pressure ( DBP ) ⩾95 and ⩽105 mm Hg , stable NIDDM , serum creatinine between 1.6 and 3.0 mg/dl and persistent UAE > 300 and < 2000 mg/24 h. after a 3-month preliminary observation period , during which patients began a low-protein , low-sodium diet , and a subsequent 4-week run-in period on placebo , patients were r and omly treated with ramipril 5 mg or nitrendipine 20 mg for 2 years . both drugs similarly reduced bp without affecting glucose homeostasis . in the ramipril group uae significantly decreased after only 3 months of treatment , whereas in the nitrendipine group a significant although lesser reduction in uae was observed only after 1 year . during the second year the uae% change was not statistically different between the two treatments . serum creatinine and creatinine clearance showed no significant change with both drugs . the progression of renal insufficiency as assessed by the rate of reduction of creatinine clearance over the 2 years of the study was similar in the ramipril and the nitrendipine groups . in conclusion both ramipril and nitrendipine were associated with a decrease in uae although such a reduction was earlier and more marked with ramipril . the decline of renal function did not differ significantly between the two treatments 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 BACKGROUND It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure . METHODS We r and omly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan ( 300 mg daily ) , amlodipine ( 10 mg daily ) , or placebo . The target blood pressure was 135/85 mm Hg or less in all groups . We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration , the development of end-stage renal disease , or death from any cause . We also compared them with regard to the time to a secondary , cardiovascular composite end point . RESULTS The mean duration of follow-up was 2.6 years . Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group ( P=0.02 ) and 23 percent lower than that in the amlodipine group ( P=0.006 ) . The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group ( P=0.003 ) and 37 percent lower in the irbesartan group than in the amlodipine group ( P<0.001 ) . Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups ( P=0.07 for both comparisons ) . These differences were not explained by differences in the blood pressures that were achieved . The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group ( P=0.008 ) and 21 percent more slowly than in the amlodipine group ( P=0.02 ) . There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point . CONCLUSIONS The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes . This protection is independent of the reduction in blood pressure it causes The effects of long-term treatment with captopril and conventional therapy on albuminuria and metabolic parameters were compared in 74 hypertensive type II diabetics with normal serum creatinine . Patients were treated double-blind with either captopril monotherapy or combined with hydrochlorothiazide or therapy with metoprolol , hydrochlorothiazide , or both for 36 months . The treatment was titrated to achieve goal diastolic blood pressure of < or = 85 mm Hg . The reductions in blood pressures during treatment were similar in patients with ( n = 21 ) and without ( n = 53 ) microalbuminuria treated with either captopril or conventional therapy . No significant changes in albuminuria occurred in normoalbuminuric patients with either therapy . Although albuminuria fell in nearly all patients with microalbuminuria treated with captopril , it rose in eight of 12 patients on conventional therapy , with macroalbuminuria developing in two of them . Renal function was preserved by both types of treatment in both patient groups . Long-term treatment with either conventional therapy or captopril did not alter metabolic variables . We conclude that captopril alone or in combination decreases albuminuria and prevents the development of macroalbuminuria in hypertensive type II diabetics with persistent microalbuminuria . The renoprotective effect of this agent , however , remains to be demonstrated with longer term data on renal function . Aggressive antihypertensive treatment with either captopril or conventional therapy appears to be effective in preventing the onset of microalbuminuria in most normoalbuminuric patients . In contrast , with previous short-term studies , the use of converting enzyme inhibitors or conventional therapy did not cause adverse metabolic effects Aims To assess the efficacy of an angiotensin converting enzyme ( ACE ) inhibitor ( perindopril ) , a dihydropyridine calcium channel blocker ( sustained release nifedipine ) and placebo in preventing the progression of albuminuria and decline in glomerular filtration rate ( GFR ) in patients with Type 2 diabetes and microalbuminaria Abstract Objective : To determine whether tight control of blood pressure with either a β blocker or an angiotensin converting enzyme inhibitor has a specific advantage or disadvantage in preventing the macrovascular and microvascular complications of type 2 diabetes . Design : R and omised controlled trial comparing an angiotensin converting enzyme inhibitor ( captopril ) with a β blocker ( atenolol ) in patients with type 2 diabetes aim ing at a blood pressure of < 150/<85 mm Hg . Setting : 20 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Subjects : 1148 hypertensive patients with type 2 diabetes ( mean age 56 years , mean blood pressure 160/94 mm Hg ) . Of the 758 patients allocated to tight control of blood pressure , 400 were allocated to captopril and 358 to atenolol . 390 patients were allocated to less tight control of blood pressure . Main outcome measures : Predefined clinical end points , fatal and non-fatal , related to diabetes , death related to diabetes , and all cause mortality . Surrogate measures of microvascular and macrovascular disease included urinary albumin excretion and retinopathy assessed by retinal photography . Results : Captopril and atenolol were equally effective in reducing blood pressure to a mean of 144/83 mm Hg and 143/81 mm Hg respectively , with a similar proportion of patients ( 27 % and 31 % ) requiring three or more antihypertensive treatments . More patients in the captopril group than the atenolol group took the allocated treatment : at their last clinic visit , 78 % of those allocated captopril and 65 % of those allocated atenolol were taking the drug ( P<0.0001 ) . Captopril and atenolol were equally effective in reducing the risk of macrovascular end points . Similar proportions of patients in the two groups showed deterioration in retinopathy by two grade s after nine years ( 31 % in the captopril group and 37 % in the atenolol group ) and developed clinical grade albuminuria ≥300 mg/l ( 5 % and 9 % ) . The proportion of patients with hypoglycaemic attacks was not different between groups , but mean weight gain in the atenolol group was greater ( 3.4 kg v 1.6 kg ) . Conclusion : Blood pressure lowering with captopril or atenolol was similarly effective in reducing the incidence of diabetic complications . This study provided no evidence that either drug has any specific beneficial or deleterious effect , suggesting that blood pressure reduction in itself may be more important than the treatment used OBJECTIVE The Appropriate Blood Pressure Control in Diabetes ( ABCD ) Trial is a prospect i ve r and omized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on the incidence and progression of type 2 diabetic complications . The current article discusses the results of 5.3 years of follow-up of 470 patients with hypertension and evaluates the effects of intensive and moderate blood pressure therapy using nisoldipine versus enalapril as the initial antihypertensive medication for nephropathy , retinopathy , and neuropathy . RESEARCH DESIGN AND METHODS The 470 hypertensive subjects , defined as having a baseline diastolic blood pressure of > or = 90 mmHg , were r and omized to intensive blood pressure control ( diastolic blood pressure goal of 75 mmHg ) versus moderate blood pressure control ( diastolic blood pressure goal of 80 - 89 mmHg ) . RESULTS The mean blood pressure achieved was 132/78 mmHg in the intensive group and 138/86 mmHg in the moderate control group . During the 5-year follow-up period , no difference was observed between intensive versus moderate blood pressure control and those r and omized to nisoldipine versus enalapril with regard to the change in creatinine clearance . After the first year of antihypertensive treatment , creatinine clearance stabilized in both the intensive and moderate blood pressure control groups in those patients with baseline normo- or microalbuminuria . In contrast , patients starting with overt albuminuria demonstrated a steady decline in creatinine clearance of 5 - 6 ml.min-1.1.73 m-2 per year throughout the follow-up period whether they were on intensive or moderate therapy . There was also no difference between the interventions with regard to individuals progressing from normoalbuminuria to microalbuminuria ( 25 % intensive therapy vs. 18 % moderate therapy , P = 0.20 ) or microalbuminuria to overt albuminuria ( 16 % intensive therapy vs. 23 % moderate therapy , P = 0.28 ) . Intensive therapy demonstrated a lower overall incidence of deaths , 5.5 vs. 10.7 % , P = 0.037 . Over a 5-year follow-up period , there was no difference between the intensive and moderate groups with regard to the progression of diabetic retinopathy and neuropathy . In addition , the use of nisoldipine versus enalapril had no differential effect on diabetic retinopathy and neuropathy . CONCLUSIONS Blood pressure control of 138/86 or 132/78 mmHg with either nisoldipine or enalapril as the initial antihypertensive medication appeared to stabilize renal function in hypertensive type 2 diabetic patients without overt albuminuria over a 5-year period . The more intensive blood pressure control decreased all-cause mortality Abstract Objective To investigate whether a low dose of the angiotensin converting enzyme ( ACE ) inhibitor ramipril lowers cardiovascular and renal events in patients with type 2 diabetes who have microalbuminuria or proteinuria . Design R and omised , double blind , parallel group trial comparing ramipril ( 1.25 mg/day ) with placebo ( on top of usual treatment ) for cardiovascular and renal outcomes for at least three years . Setting Multicentre , primary care study conducted mostly by general practitioners in 16 European and north African countries . Participants 4912 patients with type 2 diabetes aged > 50 years who use oral antidiabetic drugs and have persistent microalbuminuria or proteinuria ( urinary albumin excretion 20 mg/l in two consecutive sample s ) , and serum creatinine ≤ 150 μmol/l . Main outcome measures The primary outcome measure was the combined incidence of cardiovascular death , non-fatal myocardial infa rct ion , stroke , heart failure leading to hospital admission , and end stage renal failure . Results Participants were followed for 3 to 6 ( median 4 ) years . There were 362 primary events among the 2443 participants taking ramipril ( 37.8 per 1000 patient years ) and 377 events among the 2469 participants taking placebo ( 38.8 per 1000 patient years ; hazard ratio 1.03 ( 95 % confidence interval 0.89 to 1.20 , P = 0.65 ) ) . None of the components of the primary outcome was reduced . Ramipril lowered systolic and diastolic blood pressures ( by 2.43 and 1.06 mm Hg respectively after two years ) and favoured regression from microalbuminuria ( 20 - 200 mg/l ) or proteinuria ( > 200mg/l ) to normal level ( < 20 mg/l ) or microalbuminuria ( P < 0.07 ) in 1868 participants who completed the study . Conclusions Low dose ( 1.25 mg ) ramipril once daily has no effect on cardiovascular and renal outcomes of patients with type 2 diabetes and albuminuria , despite a slight decrease in blood pressure and urinary albumin . The cardiovascular benefits of a daily higher dose ( 10 mg ) ramipril observed elsewhere are not found with an eightfold lower daily dose BACKGROUND Diabetic retinopathy remains a leading cause of visual loss in people of working age . We examined whether c and esartan treatment could slow the progression and , secondly , induce regression of retinopathy in people with type 2 diabetes . METHODS We did a r and omised , double-blind , parallel-group , placebo-controlled trial in 309 centres worldwide . We recruited normoalbuminuric , normotensive , or treated hypertensive people with type 2 diabetes with mild to moderately severe retinopathy and assigned them to c and esartan 16 mg once a day or placebo . After a month , the dose was doubled to 32 mg once per day . Investigators and patients were unaware of the treatment allocation status . Progression of retinopathy was the primary endpoint , and regression was a secondary endpoint . Analysis was by intention to treat . The trial is registered with Clinical Trials.gov , number NCT00252694 . FINDINGS 1905 participants ( aged 37 - 75 years ) were r and omised to c and esartan ( n=951 ) or placebo ( n=954 ) . 161 ( 17 % ) patients in the c and esartan group and 182 ( 19 % ) in the placebo group had progression of retinopathy by three steps or more on the Early Treatment Diabetic Retinopathy Study scale . The risk of progression of retinopathy was non-significantly reduced by 13 % in patients on c and esartan compared with those on placebo ( hazard ratio [ HR ] 0.87 , 95 % CI 0.70 - 1.08 , p=0.20 ) . Regression on active treatment was increased by 34 % ( 1.34 , 1.08 - 1.68 , p=0.009 ) . HRs were not attenuated by adjustment for baseline risk factors or changes in blood pressure during the trial . An overall change towards less severe retinopathy by the end of the trial was observed in the c and esartan group ( odds 1.17 , 95 % CI 1.05 - 1.30 , p=0.003 ) . Adverse events did not differ between the treatment groups . INTERPRETATION Treatment with c and esartan in type 2 diabetic patients with mild to moderate retinopathy might induce improvement of retinopathy BACKGROUND Microalbuminuria in diabetes is strongly predictive of nephropathy , end-stage renal disease , and premature cardiovascular morbidity and mortality . Effective preventive therapies are therefore a clinical priority . OBJECTIVE To determine whether the angiotensin-receptor blocker c and esartan compared with placebo affects microalbuminuria incidence or rate of change in albuminuria in type 1 and type 2 diabetes . DESIGN 3 r and omized trials of the DIRECT ( Diabetic Retinopathy C and esartan Trials ) Program . SETTING 309 secondary care centers . PATIENTS 3326 and 1905 patients with type 1 and type 2 diabetes , respectively . Most were normotensive , and all had normoalbuminuria ( median urinary albumin excretion rate , 5.0 microg/min ) . INTERVENTION C and esartan , 16 mg/d increasing to 32 mg/d , versus placebo . Assignment was done central ly using an interactive voice-response system . Patients , caregivers , and research ers were blinded to treatment assignment . During a median follow-up of 4.7 years , 793 patients discontinued therapy and 63 were lost to follow-up . MEASUREMENTS Urinary albumin excretion rate , assessed annually by 2 overnight collection s ; if it was 20 microg/min or greater , then 2 further collection s were done . The primary end point was new microalbuminuria ( 3 or 4 collection s of urinary albumin excretion rate > or=20 microg/min ) . The secondary end point was rate of change in albuminuria . RESULTS Individual and pooled results of the 3 trials showed that c and esartan had little effect on risk for microalbuminuria ( pooled hazard ratio , 0.95 [ 95 % CI , 0.78 to 1.16 ] ; P = 0.60 ) . Pooled results showed that the annual rate of change in albuminuria was 5.53 % lower ( CI , 0.73 % to 10.14 % ; P = 0.024 ) with c and esartan than with placebo . LIMITATIONS Investigators recruited mainly normotensive patients or patients with well-controlled hypertension who were at low overall vascular risk , which result ed in a low rate of microalbuminuria . Studies were powered for retinal and not renal end points . CONCLUSION C and esartan , 32 mg/d , for 4.7 years did not prevent microalbuminuria in mainly normotensive patients with type 1 or type 2 diabetes BACKGROUND Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease . We investigated whether treatment with an angiotensin-receptor blocker ( ARB ) would delay or prevent the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria . METHODS In a r and omized , double-blind , multicenter , controlled trial , we assigned 4447 patients with type 2 diabetes to receive olmesartan ( at a dose of 40 mg once daily ) or placebo for a median of 3.2 years . Additional antihypertensive drugs ( except angiotensin-converting-enzyme inhibitors or ARBs ) were used as needed to lower blood pressure to less than 130/80 mm Hg . The primary outcome was the time to the first onset of microalbuminuria . The times to the onset of renal and cardiovascular events were analyzed as secondary end points . RESULTS The target blood pressure ( < 130/80 mm Hg ) was achieved in nearly 80 % of the patients taking olmesartan and 71 % taking placebo ; blood pressure measured in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group . Microalbuminuria developed in 8.2 % of the patients in the olmesartan group ( 178 of 2160 patients who could be evaluated ) and 9.8 % in the placebo group ( 210 of 2139 ) ; the time to the onset of microalbuminuria was increased by 23 % with olmesartan ( hazard ratio for onset of microalbuminuria , 0.77 ; 95 % confidence interval , 0.63 to 0.94 ; P=0.01 ) . The serum creatinine level doubled in 1 % of the patients in each group . Slightly fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events--81 of 2232 patients ( 3.6 % ) as compared with 91 of 2215 patients ( 4.1 % ) (P=0.37)--but a greater number had fatal cardiovascular events--15 patients ( 0.7 % ) as compared with 3 patients ( 0.1 % ) ( P=0.01 ) , a difference that was attributable in part to a higher rate of death from cardiovascular causes in the olmesartan group than in the placebo group among patients with preexisting coronary heart disease ( 11 of 564 patients [ 2.0 % ] vs. 1 of 540 [ 0.2 % ] , P=0.02 ) . CONCLUSIONS Olmesartan was associated with a delayed onset of microalbuminuria , even though blood-pressure control in both groups was excellent according to current st and ards . The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern . ( Funded by Daiichi Sankyo ; Clinical Trials.gov number , NCT00185159 . ) The effects of 3 , 15 , and 27 months of treatment with nitrendipine ( 10 to 40 mg/day ) and enalapril ( 5 to 20 mg/day ) on diastolic blood pressure ( DBP ) , overnight urinary albumin excretion ( UAE ) rate , glomerular filtration rate ( GFR ) , and renal plasma flow ( RPF ) were studied prospect ively in a parallel group design in 13 microalbuminuric non-insulin dependent diabetic patients with mild hypertension and biopsy-proven diabetic glomerulopathy . Throughout the study period DBP decreased in both groups to < 95 mm Hg . At three months UAE , GFR , and RPF did not change significantly . At 15 and 27 months UAE ( microgram/min , geometric mean and 95 % C.I. ) decreased respectively from 47.4 ( 23.4 to 95.9 ) to 28.6 ( 10.3 to 79.4 ) , and to 22.3 ( 10.9 to 45.2 ; P = 0.0005 ) with nitrendipine , and from 58.3 ( 30.3 to 110.9 ) to 44.1 ( 22.9 to 84.8 ) , and to 14.7 ( 4.4 to 49.3 ; P = 0.0025 ) with enalapril . Four patients in each group were normoalbuminuric at 27 months and none became macroalbuminuric . At 15 months the GFR ( ml/min/1.73 m2 , mean + /- SD ) increased from 69.5 + /- 15.2 to 96.6 + /- 22.0 ( P < 0.05 ) with nitrendipine and from 58.9 + /- 10.7 to 78.5 + /- 11.0 ( P < 0.05 ) with enalapril . At 27 months the GFR was still numerically higher that at baseline either with nitr and ipine ( 81.2 + /- 7.8 ) and with enalapril ( 79.9 + /- 17.7 ) ( P = 0.7 ) . The RPF ( ml/min/1.73 m2 , mean + /- SD ) at baseline and at 27 months was comparable either with nitrendipine ( 456.6 + /- 165.3 vs. 400.9 + /- 112.9 ) and with enalapril ( 400.3 + /- 81.3 vs. 399.0 + /- 123.7 ) . Both treatments were well tolerated . This is the first evidence that long-term effective control of arterial blood pressure by a calcium channel blocker or by an angiotensin converting enzyme inhibitor , in addition to reducing albuminuria , also improves GFR in incipient nephropathy Objectives To test whether microalbuminuria in patients with type 2 diabetes and hypertension is primarily dependent on the severity of hypertension , and to compare the effectiveness of two antihypertensive drugs with opposite effects on the renin – angiotensin system [ the diuretic , indapamide sustained release ( SR ) , and an angiotensin-converting enzyme inhibitor , enalapril ] in reducing microalbuminuria . Design A multinational , multicentre , controlled , double-blind , double-dummy , r and omized , two-parallel-groups study over 1 year . Methods After a 4-week placebo run-in period , 570 patients ( ages 60.0 ± 9.9 years , 64 % men ) with type 2 diabetes , essential hypertension [ systolic blood pressure ( SBP ) 140–180 mmHg , and diastolic blood pressure ( DBP ) < 110 mmHg ] , and persistent microalbuminuria ( 20–200 μg/min ) were allocated r and omly to groups to receive indapamide SR 1.5 mg ( n = 284 ) or enalapril 10 mg ( n = 286 ) once a day . Amlodipine , atenolol , or both were added , if necessary , to achieve the target blood pressure of 140/85 mmHg . Results There was a significant reduction in the urinary albumin : creatinine ratio . Mean reductions were 35 % [ 95 % confidence interval ( CI ) 24 to 43 ] and 39 % ( 95 % CI 30 to 47 % ) in the indapamide SR and enalapril groups , respectively . Equivalence was demonstrated between the two groups [ 1.08 ( 95 % CI 0.89 to 1.31 % ) ; P = 0.01 ] . The reductions in mean arterial pressure ( MAP ) were 16.6 ± 9.0 mmHg for the indapamide SR group and 15.0 ± 9.1 mmHg for the enalapril group ( NS ) ; the reduction in SBP was significantly greater ( P = 0.0245 ) with indapamide SR . More than 50 % of patients in each group required additional antihypertensive therapy , with no differences between groups . Both treatments were well tolerated . Conclusions Indapamide-SR-based therapy is equivalent to enalapril-based therapy in reducing microalbuminuria with effective blood pressure reduction in patients with hypertension and type 2 diabetes Thirty-nine hypertensive patients with type 2 diabetes mellitus were followed under long-term treatment ( mean , 20.7 months ) with manidipine hydrochloride , a Ca antagonist , or delapril hydrochloride , an ACE inhibitor , at nine institutions . Both the treatments showed similar antihypertensive effects , although slight but significantly larger decreases were observed in systolic and mean blood pressures at months 12 and 24 in the patients treated with manidipine ( P < 0.02 ) . The urinary albumin excretion index ( AEI ) tended to increase throughout the study in both treatment groups , but no significant difference in AEI was observed between the two treatment groups at any time point . Overt albuminuria developed in four patients on manidipine but did not appear in any of the patients on delapril . The risk of progression to overt albuminuria was significantly different between manidipine and delapril groups ( P = 0.011 ) . No increase in serum creatinine ( Cr ) was observed with delapril . The average excretion indexes of tubular markers such as beta2-microglobulin , alpha1-microglobulin , and NAG tended to be higher in the patients on manidipine than in those on delapril . Taken in sum , these findings suggest that the ACE inhibitor delapril is more beneficial than the Ca antagonist manidipine in the treatment of diabetic renal diseases via mechanisms other than the blood pressure regulation , partly through their different effects on tubular function . In conclusion , delapril was significantly more effective than manidipine in inhibiting progression to overt albuminuria in hypertensive type 2 diabetes mellitus patients BACKGROUND Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries . Duration of diabetes , blood pressure values , and metabolic status are the major determinants of the course of nephropathy , and microalbuminuria is the hallmark of its onset . Angiotensin-converting enzyme inhibitors offer important renoprotection to hypertensive and normotensive patients with insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus . Our study extends previous observations for duration and the effect of angiotensin-converting enzyme inhibition on advanced nephropathy . METHODS Double-blinded ( first phase ) and open ( second phase ) r and omized controlled study of 7 years . Ninety-four normotensive patients with non-insulin-dependent diabetes mellitus whose serum creatinine levels were lower than 123.76 mumol/L ( 1.4 mg/dL ) and who had microalbuminuria ( 30 to 300 mg/24 h ) were given enalapril maleate , 10 mg/d , or placebo , for 5 years . For 2 more years they were followed up openly and given the choice to receive enalapril or no treatment . RESULTS In the enalapril-treated patients , albuminuria remained stable for 7 years . An increase from ( mean + /- SD ) 123 + /- 58 to 310 + /- 167 mg/24 h occurred in the untreated group after 5 years , and a further increase to ( mean + /- SD ) 393 + /- 223 mg/24 h occurred after 7 years . Reciprocal creatinine was unchanged in treated patients for 7 years ; in the untreated patients , the mean decline was 13 % at 5 years and 16 % at 7 years . Treatment with enalapril result ed in an absolute risk reduction of 42 % for nephropathy to develop during 7 years ( 95 % confidence interval , 15 % to 69 % ; P < .001 , Student 's t test ) . Glycosylated hemoglobin and body mass index remained unchanged . CONCLUSIONS Angiotensin-converting enzyme inhibition offers long-term protection against the development of nephropathy in normotensive patients with noninsulin-dependent diabetes mellitus who have microalbuminuria , and it stabilizes renal function in previously untreated patients with impaired renal function . Discontinuation of treatment results in renewed progression of nephropathy OBJECTIVE This study determines the long-term efficacy of the ACE inhibitor , enalapril , in reducing the progression of microalbuminuria to clinical albuminuria in normotensive patients with type 2 diabetes . RESEARCH DESIGN AND METHODS There were 103 normotensive type 2 diabetic patients with persistent albumin excretion rate ( AER ) 20–200 micrograms/min and normal renal function followed for 5 years in a prospect i ve r and omized single-blind placebo-controlled trial . AER , blood pressure , fasting plasma glucose , and HbA1 were measured every 3–4 months and glomerular filtration rate ( GFR ) , renal plasma flow ( RPF ) , and urinary urea every 12 months . RESULTS In the patients treated with enalapril , AER decreased from 55 ± 33 to 20 ± 59 micrograms/min ( geometric mean ± SD ) , whereas in the placebo group , AER increased from 53 ± 31 to 85 ± 90 micrograms/min after 5 years . Within 5 years , 7.7 % ( 4/52 ) of enalapril-treated subjects and 23.5 % ( 12/51 ) of placebo-treated subjects progressed to clinical albuminuria defined as AER > 200 micrograms/min and at least 34 % above baseline ( risk reduction = 66.7 % , P < 0.001 ) . AER increased at an annual rate of 12.3 % ( 95 % CI 9.8–14.9 ) in the placebo group , while it declined by 16.7 % ( 95 % CI −18.3 to −15.2 ) in the enalapril group ( P < 0.001 ) . In addition , 8 of the 12 placebo-treated patients had evidence of coronary artery disease . The rest of the parameters remained practically unchanged in the two groups . CONCLUSIONS After 5 years of therapy with enalapril , compared with placebo , normotensive subjects with type 2 diabetes experienced significantly less progression of microalbuminuria to clinical albuminuria , reduced AER , and preserved GFR The Japan Multicenter Investigation of Antihypertensive Treatment for Nephropathy in Diabetics ( J-MIND ) study was conducted to evaluate the effect of nifedipine retard or enalapril on nephropathy in hypertensive patients with type 2 diabetes . A total of 436 patients with normoalbuminuria [ urinary albumin excretion rate ( AER ) < 30 mg/day ] or microalbuminuria [ AER : 30 - 300 mg/day ] were r and omized to receive nifedipine retard or enalapril and were followed for 24 months . There were no differences in baseline characteristics between the two groups ( the mean AER was 45 and 42 mg/day , respectively ) . Intent-to-treat analysis showed no significant difference in AER after 2 years , although the mean AER increased to 64 and 74 mg/day in the nifedipine retard and enalapril groups , respectively . The AER increased in patients with normoalbuminuria , whereas it did not change in those with microalbuminuria . There were no differences between the two groups with respect to progression from normoalbuminuria to microalbuminuria , progression from microalbuminuria to overt proteinuria , and regression from microalbuminuria to normoalbuminuria . The incidence of cardiovascular events was also similar in both groups . In conclusion , nifedipine retard and enalapril had a similar effect on nephropathy in hypertensive type 2 diabetic patients without overt proteinuria Diabetic nephropathy is the single most important cause of end-stage renal failure in the western world . It accounts for 15 % to 25 % of all renal failure in patients receiving chronic dialysis [ 1 ] . About 40 % of type I and 20 % of type II diabetics develop clinical ly important nephropathy [ 2 - 4 ] . However , the ratio of type II to type I diabetics is 10 to 1 , and the number of patients with chronic renal failure due to type II disease exceeds that of type I [ 4 - 6 ] . Therefore , an obvious need exists to evaluate treatments that may delay the progress of nephropathy in type II diabetes . However , most studies of diabetic renal disease have hitherto focused on type I diabetes . Available data suggest that effective antihypertensive treatment is the best inhibitor of diabetic nephropathy [ 7 - 10 ] . Angiotensin-converting enzyme inhibitors have been found more effective than placebo and -adrenergic blocking agents in hypertensive as well as in normotensive diabetics with early and advanced nephropathy [ 11 - 15 ] . Some classes of calcium antagonists effectively decrease urinary protein excretion and may preserve renal function . However , analysis of several studies shows that , although the effects of angiotensin-converting enzyme inhibitors are consistent , those of calcium antagonists vary [ 16 - 18 ] . Short-term studies showed a clear antiproteinuric effect of captopril and of enalapril on the diabetic kidney , probably independent of the antihypertensive effect of these agents [ 14 , 15 , 19 ] . However , the outcome of long-term intervention and the possibility of a true alteration of the natural course of the disease were unknown . We did a relatively long-term , 5-year study of the effect of the angiotensin-converting enzyme inhibitor , enalapril , on the course of diabetic nephropathy in normotensive , type II diabetic patients with microalbuminuria and normal renal function . Our report describes a r and omized , placebo-controlled , double-blind study on 94 diabetic patients . Methods Patients A total of 108 patients with type II diabetes mellitus , diagnosed according to World Health Organization criteria [ 20 ] who attended six clinics in the Tel Aviv area were recruited during 1986 and gave informed consent to participate in the study . The inclusion criteria were as follows : age less than 50 years ; duration of diabetes mellitus of less than 10 years with no evidence of systemic , renal , cardiac , or hepatic diseases ; body mass index less than 27 kg/m2 ; normal blood pressure values on two consecutive examinations ( systolic , 140 mm Hg ; diastolic , 90 mm Hg ; mean blood pressure < 107 mm Hg ) ; serum creatinine , < 123 mol/L ( 1.4 mg/dL ) ; and microalbuminuria ( urinary protein excretion of 30 to 300 mg/24 h ) on two consecutive visits without evidence of urinary tract infection . Initially , there were 49 men and 59 women , ages 34 to 49 years ( mean age [ SD ] , 44 4 years ) . The duration of diabetes was 0.5 to 9.1 years ( mean duration [ SD ] , 6.7 1.6 years ) . Sixteen patients received insulin , 43 were taking oral hypoglycemic agents , and 49 were using diet to control their diabetes . Protocol The protocol was approved by the hospital review board . After a 2-month pretreatment period , the patients were r and omly allocated to receive either 10 mg enalapril ( Teva Pharmaceutical Industries , Ltd. , Petach Tikwa , Israel ) daily or placebo in a double-blind manner . The placebo tablets were similar but not identical to enalapril . R and omization was done using a table of r and om numbers [ 21 ] . The follow-up period was terminated , for each patient , exactly 5 years after his or her r and omization , and the data were su bmi tted for evaluation . The patients were seen by their family physicians approximately every 3 to 4 months . On these visits , fasting blood glucose , glycosylated hemoglobin , serum creatinine , serum electrolyte levels , and albuminuria in 24-hour urine sample s were determined . Blood pressure was measured by mercury sphygmomanometers with the patients sitting after a 5-minute rest ; the average of two determinations was recorded . The diastolic pressure was determined at Korotkoff phase V. If systolic blood pressure values of 145 mm Hg , or diastolic values of 95 mm Hg , were found on two consecutive occasions , treatment with long-acting nifedipine ( Pressolate , Agis Industries Ltd. , Yeruham , Israel ) was initiated . Funduscopy was done yearly by an ophthalmologist , and the presence of diabetic retinopathy was recorded . Measurements Glucose and creatinine levels were determined by routine automated methods . Glycosylated hemoglobin levels were measured by affinity chromatography with a commercial kit ( Isolab , Biochemical Methodology , Drower 4350 , Akron , Ohio ) . The albumin excretion rate was measured on 24-hour urine sample s by an automated immunoturbidimetric assay [ 22 ] . Sixteen to 20 fasting blood glucose determinations and 15 to 20 glycosylated hemoglobin values were available for each patient . For each patient , the correlation coefficients between fasting blood glucose and glycosylated hemoglobin levels were between 0.60 and 0.84 . The mean blood pressure values were calculated for each patient ( mean pressure defined as diastolic value plus one third of the pulse pressure ) . The reciprocal creatinine value ( 100/creatinine value ) was calculated for each visit [ 23 ] , and the decline in renal function was expressed as a percentage of the initial value . The course of renal function , of the mean blood pressure , and of urinary protein excretion were plotted against time ( separately ) for the enalapril and the placebo groups . Statistical Analysis All data were expressed as mean ( SD ) and ranges . Significance was defined as P < 0.05 . To test for adequate r and omization , the enalapril and placebo groups were compared with respect to mean age , mean duration of diabetes , as well as mean baseline values of albuminuria , serum creatinine , glycosylated hemoglobin , and mean blood pressure using pooled variance Student t-tests for independent groups as well as one-way analysis of variance . To compare the annual means of the various measurements between the two groups and within each group , one between-group factor and one repeated measures factor were used in analysis of variance . The rate of decrease of reciprocal creatinine levels and the rate of increase of albuminuria were calculated by linear regression analysis . Results Five patients , 2 taking enalapril and 3 taking placebo left the study during the first year . Six patients ( 4 taking enalapril and 2 taking placebo ) developed a disturbing cough , and the treatment was discontinued . Three patients ( 1 on enalapril and 2 on placebo ) were lost to follow-up during the third and fourth years . The final analysis was therefore done on 94 patients , of whom 49 received enalapril and 45 received placebo . Age , male/female ratio , duration of diabetes , and the other baseline data of the two groups are shown in Table 1 . No statistically significant differences existed between the initial characteristics of the enalapril and the placebo groups . Table 1 . Baseline Data from 94 Type II Diabetic Patients with Microalbuminuria * During the first year of treatment , the urinary albumin excretion in the enalapril group decreased from an initial mean of 143 mg/24 h to an annual mean of 122 mg/24 h. Values greater than 300 mg/24 h were recorded in only two patients . Subsequently , a minimal but steady increase occurred in mean daily albumin excretion of these patients , with a fourth-year mean of 136 mg/24 h and a fifth-year mean of 140 mg/24 h. In six patients , albuminuria exceeded 300 mg/24 h. In contrast , among the placebo-treated patients , a steady , gradual increase occurred in mean daily albuminuria . The initial albumin value was 123 mg/24 h , the first-year mean was 134 mg/24 h , and the fifth-year value was 310 mg/24 h. Albumin values were greater than 300 mg/24 h in 19 patients and greater than 1 mg/24 h in three patients . The difference between the mean values of daily albuminuria in the two groups became statistically significant after the first year . However , the difference in the rate of change in proteinuria from baseline was statistically significant at the end of the first year ( P < 0.05 ) . These data are shown in Figure 1 and are numerically detailed in the Appendix Table . If the development of overt proteinuria ( 300 mg/24 h ) is considered clinical ly important , the risk for developing this degree of proteinuria within 5 years of follow-up was 19/45 ( 42 % ) in the placebo group compared with 6/49 ( 12 % ) in the enalapril group . Therefore , enalapril treatment result ed in an absolute risk reduction of 30 percentage points for the development of overt proteinuria ( 95 % CI , 15 % to 45 % ; P < 0.001 ) for a 5-year period . Appendix Table . Initial and Annual Averages of Blood Chemistry Values for the 5-Year Follow-up in the Enalapril- and Placebo-Treated Groups * Figure 1 . Proteinuria during 5-year follow-up in diabetics treated with enalapril or placebo . P P P Renal function , expressed as reciprocal creatinine ( 100/cr ) remained unchanged in the enalapril group during the first 2 years of follow-up . From the third year onward , a small , nonsignificant but systematic decrease was recorded . The decrease was 1 % of the initial value during the 5 years . In the placebo-treated group , a gradual , steady decrease of about 2 % occurred in renal function each year . The difference between the initial and mean fifth-year values was 13 % ( P < 0.05 ) . The difference between the mean rate of decrease of reciprocal creatinine among the enalapril- and the placebo-treated groups became significant after the second year . These data are shown in Figure 2 and are outlined in the Appendix Table . Figure 2 . Reciprocal creatinine ( 100/cr ) levels expressed as percentage of initial value , during 5 years of follow-up in placebo- and enalapril-treated type II diabetics . P P The mean blood pressure in the enalapril-treated patients decreased slightly from an initial value of 99 mm Hg to 96 mm Hg during the first Treatment of hypertension with ACE inhibitors in diabetic patients reduces proteinuria and slows progression of nephropathy compared with agents that do not maintain declines in proteinuria . Calcium channel blockers ( CCBs ) have variable effects on proteinuria ; their long-term effects on progression of diabetic nephropathy are not known . The current study examines the hypothesis that CCBs that maintain reductions in proteinuria slow progression of nephropathy associated with non-insulin dependent diabetes mellitus ( NIDDM ) by a degree comparable to ACE inhibitors , given similar levels of blood pressure control . To test this hypothesis we r and omized 52 patients with NIDDM associated nephropathy and hypertension , mean age of 63 + /- 8 years , to either the ACE inhibitor , lisinopril ( N = 18 ) , nondihydropyridine CCBs ( NDCCBs ) , verapamil SR ( N = 8) or diltiazem SR ( N = 10 ) , or the beta blocker , atenolol ( N = 16 ) . Goal blood pressure was < or = 140/90 mm Hg . Patients were followed for a mean period of 63 + /- 7 months . The primary end point was change in creatinine clearance ( CCr ) slope in each group . There was no significant difference in mean arterial pressure reduction among the groups over the study period ( P = 0.14 ) . The mean rate of decline in CCr was greatest in the atenolol group ( -3.48 ml/min/year/1.73 m2 ; P < 0.0001 ) . There was no difference in the CCr slopes between lisinopril and NDCCBs groups ( P = 0.36 ) . Proteinuria was reduced to a similar extent in the lisinopril and NDCCBs groups ( P > 0.99 ) . Therefore , in persons with renal insufficiency secondary to NIDDM , similar levels of blood pressure control with either lisinopril or NDCCBs slowed progression of renal disease to a greater extent than atenolol . Moreover , this enhanced slowing of renal disease progression correlated with sustained and significant reductions in proteinuria , findings not observed in the atenolol group The Ramipril Efficacy in Nephropathy ( REIN ) study found that angiotensin-converting enzyme ( ACE ) inhibitors effectively decreased proteinuria , glomerular filtration rate ( GFR ) decline ( DeltaGFR ) , and incidence of end-stage renal disease ( ESRD ) in patients with proteinuric chronic nephropathies . In this study , we prospect ively investigated the main clinical determinants of progression and response to treatment in the 352 patients enrolled into the REIN study . Mean DeltaGFR ( 0.56 + /- 0.05 [ SEM ] versus 0.21 + /- 0.05 mL/min/1.73 m(2)/mo ; P = 0.0001 ) and incidence of ESRD ( 30 % and 10 % ; P = 0.0001 ) were more than twice that in patients with proteinuria of 2 g/24 h or greater of protein compared with those with protein less than 2 g/24 h ( relative risk [ RR ] , 4.07 ; 95 % confidence interval [ CI ] , 2.20 to 7.52 ) , as well as in patients with hypertension compared with normotension ( mean DeltaGFR , 0.48 + /- 0 . 05 versus 0.22 + /- 0.05 mL/min/1.73 m(2)/mon ; P = 0.0006 ; ESRD , 25 % versus 10 % ; P = 0.004 ; RR , 3.18 ; 95 % CI , 1.38 to 7.32 ) . Hypertension at study entry ( P = 0.038 ) , greater mean blood pressure on follow-up ( P = 0.002 ) , and urinary protein excretion rate ( P = 0.0001 ) were independent predictors of faster DeltaGFR . DeltaGFR was approximately twofold faster in patients with type 2 diabetes than in those with primary glomerular disease ( P = 0.002 ; including immunoglobulin A [ IgA ] nephropathy , P = 0.009 ) ; nephrosclerosis ( P = 0.03 ) , adult polycystic kidney disease ( APKD ) , or chronic interstitial nephritis ( P = 0.006 ) . Diabetes at study entry ( P = 0 . 02 ) and greater mean blood pressure ( P = 0.0001 ) and urinary protein excretion rate ( P = 0.0001 ) on follow-up were independent predictors of faster DeltaGFR . After correction for baseline covariates , diabetes was also associated with an increased risk for progression to ESRD ( RR , 2.39 ; 95 % CI , 1.01 to 5.68 ; P < 0.05 ) . At multivariate analyses , ramipril significantly decreased DeltaGFR ( regression coefficient,-0.23 + /- 0.11 [ SEM ] ; P = 0.036 ) and ESRD ( RR , 2.08 ; 95 % CI , 1.21 to 3.57 ; P = 0.008 ) in patients with baseline proteinuria of 2 g/24 h or greater of protein , and the renoprotective effect increased for increasing levels of proteinuria . Ramipril decreased DeltaGFR to a similar extent in normotensive and hypertensive patients ( -0.14 + /- 0.11 versus -0.14 + /- 0.09 ) and significantly limited ESRD in hypertensive patients ( RR , 2.03 ; 95 % CI , 1.26 to 3 . 26 ; P = 0.004 ) . DeltaGFR was decreased by 42 % in primary glomerular disease ( P = 0.017 ) , by 35 % in IgA nephropathy , and by 37 % in nephrosclerosis , but was not improved in type 2 diabetes , APKD , or interstitial nephritis . At multivariate analyses , ramipril significantly slowed DeltaGFR ( -0.24 + /-0.08 ; P = 0.004 ) and progression to ESRD ( RR , 2.32 ; 95 % CI , 1.36 to 3.96 ; P = 0.002 ) in patients without diabetes , but not in patients with diabetes , who tended to have a faster DeltaGFR ( + 0.62 + /- 0.44 ) on ramipril therapy . In summary , patients with proteinuria of 2 g/24 h or greater of protein , preexisting hypertension , or type 2 diabetes were faster progressors . Greater blood pressure and degree of proteinuria were the strongest determinants of faster GFR decline . The renoprotective effect of ramipril was similar in patients with normotension and hypertension . Hypertensive patients and those with proteinuria of 2 g/24 h or greater of protein , primary glomerular disease , or nephrosclerosis gained the most from ACE inhibitor treatment . During the study period , those with proteinuria less than 2 g/24 h of protein , type 2 diabetes , or polycystic kidney disease did not benefit by treatment to an appreciable extent Reduction of microalbuminuria in patients with type 2 diabetes mellitus : the Shiga Microalbuminuria Reduction Trial ( SMART ) Received for publication 8 December 2006 and accepted in revised form 2 March 2007 . Takashi Uzu , Makoto Sawaguchi , Hiroshi Maegawa , Atsunori Kashiwagi , for the Shiga Microalbuminuria Reduction Trial ( SMART ) group The concept of microalbuminuria has had a major impact on diabetes research and clinical care of patients with diabetes [ 1 - 5 ] . Initial albuminuria is regarded by most research ers as an independent predictor of subsequent progression of nephropathy and risk for cardiovascular morbidity and mortality [ 6 - 8 ] . Angiotensin-converting enzyme ( ACE ) inhibitors have been found to attenuate progression of nephropathy in both types of diabetes in hypertensive [ 9 - 12 ] and normotensive patients [ 13 - 15 ] with microalbuminuria . They were also found to lower urinary albumin excretion in normotensive and normoalbuminuric patients with type 1 diabetes [ 16 ] . The relation between albuminuria and later progression of nephropathy in these patients has not been established , possibly because of short follow-up periods . No data are available on the effect of early introduction of ACE inhibitors in normotensive and normoalbuminuric patients with type 2 diabetes mellitus . We design ed a r and omized , double-blind , placebo-controlled trial of the effect of ACE inhibition on the course of nephropathy in 156 patients with type 2 diabetes . These patients had normal blood pressure and normal urinary albumin excretion at baseline . Methods Patients Potential c and i date s were identified through the computerized records of the central regional laboratory for the northern part of the greater Tel-Aviv area . Persons with hyperglycemia and normal urinalysis results were located through their family physicians . Consent was sought once eligibility was established . Inclusion criteria were age younger than 60 years ; age 40 years or older at diagnosis ; duration of diabetes mellitus less than 10 years with no clinical evidence of malignant , autoimmune , hepatic , cardiovascular , or renal disease ; body mass index less than 30 kg/m2 ; normal blood pressure on at least two consecutive visits ( systolic pressure 140 mm Hg and diastolic pressure 90 mm Hg ; mean pressure 107 mm Hg ) ; serum creatinine concentration of 123 mol/L or less ; and urinary albumin excretion of 30 mg/24 h or less . All baseline data were obtained twice during the run-in prer and omization period . Patients were eligible only if values within the predetermined range were found on both examinations . The average of the values was used as the baseline value . A total of 255 patients who had type 2 diabetes according to World Health Organization criteria [ 17 ] and attended one of eight clinics in the greater Tel-Aviv area were found to be eligible and were contacted during 1990 and 1991 . Of these patients , 214 gave informed consent to participate . Twenty patients were excluded during the observation period : Six had blood pressure values above normal , 5 had microalbuminuria , 3 had serum creatinine concentrations above the trial criterion , 1 patient developed unstable angina pectoris , and 5 withdrew consent . Of the 194 patients included in the study , 102 were women and 92 were men ( mean age SD , 54.9 3.2 years [ range , 37 to 59 years ] ) . The known duration of diabetes was 0 to 9 years ( mean duration , 5.75 2.8 years ) . Patients were instructed to use the st and ard isocaloric diet recommended by the Israeli Diabetic Association , and 69 study patients used diet alone to control their hyperglycemia . Pharmacologic therapy for diabetes was insulin in 34 patients and oral hypoglycemic agents in 91 patients . Protocol The protocol was approved by the hospital review board . After a 2-month observation period , patients were r and omly assigned in a double-blind manner to receive enalapril ( Assia-Riezel Ltd. , Ramat-Gan , Israel ) , 10 mg/d , or placebo . Ninety-seven patients were assigned to receive enalapril , and 97 were assigned to receive placebo . R and omization was done central ly by telephone with a r and om number table [ 18 ] . Patient allocation to placebo or enalapril was recorded and kept by one of the authors . The placebo tablets were similar in appearance to the enalapril tablets . The medications , which came in sealed , numbered packages , were central ly prepared and were given to the patients at each visit by one nurse who was otherwise not involved in the study . Patients were followed by their family physicians , who were unaware of allocation . Two semiannual prescheduled visits took place each year , and interim visits were scheduled as clinical ly indicated . At the semiannual visits , hemoglobin A1c values , serum creatinine concentrations , serum electrolyte levels , and 24-hour albumin excretion and urinary creatinine concentrations were measured . Blood pressure was measured by the physicians twice at each visit by using mercury sphygmomanometers with the patients seated after a 5-minute rest ; physicians recorded the average of the two values . The diastolic pressure was determined at Korotkoff phase V. If a systolic blood pressure of 145 mm Hg or more or a diastolic blood pressure of 95 mm Hg or more was found , measurements were repeated weekly . If elevated values persisted on two consecutive visits , a long-acting calcium-channel blocker ( diltiazem or verapamil ) , hydrochlorothiazide , or both were administered . If systolic blood pressure values of 100 mm Hg or less were repeatedly found , the enalapril dosage was reduced to 5 mg/d ( half of a 10-mg enalapril tablet or half of a placebo tablet ) . Fundoscopy was done yearly by an ophthalmologist , and the presence of retinopathy was recorded . For each patient , follow-up was terminated 6 years after r and omization . Measurements All blood and urine sample s were examined by a central laboratory . Assays were not changed during the study period . Glycosylated hemoglobin values were measured by affinity chromatography with a commercial kit ( Isolab , Biochemical Methodology , Akron , Ohio ) . The normal range of this assay is a hemoglobin A1c value of 3.5 % to 5.6 % and an intra-assay and interassay coefficient of variability of less than 3 % . Urinary albumin concentration was measured twice in 24-hour urine sample s by an automated immunoturbidimetric method [ 19 ] . This procedure has intra-assay and interassay coefficients of variability of 5.9 % and 7.6 % , respectively . Creatinine concentrations were determined by using the automated method of Bartels and colleagues [ 20 ] . Creatinine clearance , normalized for 1.73 m2 of body surface area , was calculated for each visit by using the st and ard formula ( urine creatinine x urine volume/plasma creatinine ) . The mean blood pressure ( defined as the diastolic pressure plus one third of the pulse pressure ) was calculated at each visit . Statistical Analysis Data are expressed as the mean ( SD ) with ranges . A P value less than 0.05 was considered significant . On the basis of the assumptions that 15 % of normotensive , normoalbuminuric patients with type 2 diabetes will develop microalbuminuria during 6 years and that treatment with enalapril will reduce the risk for microalbuminuria by 12 % , we calculated that 69 patients were required in each group for a type 1 error of 0.05 and a power of 0.80 [ 21 ] . To test for adequate r and omization and to compare the patients who completed the trial with those who did not complete the trial , the enalapril and placebo groups and the 38 patients who dropped out were compared for mean age ; mean duration of diabetes ; and mean baseline albumin excretion , creatinine clearance , glycosylated hemoglobin value , and blood pressure by using pooled-variance Student t-tests for independent groups and one-way analysis of variance . To compare the annual means of the various measurements between the two groups and within each group , one between-group factor and one repeated- measures factor were used in analysis of variance . For variables shown to be different by analysis of variance , unpaired t-tests were used for between-group parallel annual means and paired t-tests were used for comparison of intragroup sequential annual means . The rate of decrease of creatinine clearance and the rate of increase of albumin excretion were computed by doing linear regression analysis with all of the semiannual values included in the equation . Urinary albumin values were logarithmically transformed before analysis . The degree of albuminuria at baseline was used as a covariate . The funding source had no involvement in the design , conduct , or reporting of the trial . Results Figure 1 shows the flow of participants during the trial . Thirty-eight patients did not complete the trial . Five patients died ( 3 in the enalapril group and 2 in the placebo group ) ; death was related to coronary heart disease in 3 patients , stroke in 1 patient , and ovarian carcinoma in 1 patient . Six patients violated the protocol ( 2 patients in the enalapril group stopped taking their medication for more than 6 months , and 4 patients in the placebo group took an ACE inhibitor prescribed by consultant physicians for more than 6 months ) . Ten patients were lost to follow-up ( 6 in the enalapril group and 4 in the placebo group ) . The trial medication was discontinued in 12 patients : Six developed a disturbing cough ( 4 in the enalapril group and 2 in the placebo group ) , 4 had an allergic skin reaction ( 2 in the enalapril group and 2 in the placebo group ) , 1 patient in the enalapril group developed leukopenia , and 1 patient in the placebo group developed hyperkalemia . Finally , 5 patients developed severe urinary tract infections that had a detectable influence on renal function ( 2 in the enalapril group and 3 in the placebo group ) . A total of 156 patients completed the trial , of whom 77 received enalapril and 79 received placebo . Figure 1 . Flow of participants through the trial . Baseline data for the two groups and for patients who did not complete the trial are shown in Table 1 . The baseline characteristics of patients in the study groups and those who dropped out did not differ significantly . A modest but steady decrease in hemoglobin A1c values was seen in the enalapril and the placebo groups and may reflect the change in attitude toward glucose control among family physicians in the early 1990s . However , The aim of our study was to evaluate whether inhibition of ACE ( lisinopril 10–20 mg/day ) can reduce the rate of decline in kidney function more than reducing blood pressure with conventional antihypertensive treatment ( atenolol 50–100 mg/day ) , usually in combination with a diuretic . We performed a prospect i ve , r and omized , parallel study for 42 months , double blind for the first 12 months and single blind thereafter . Forty-three ( 21 lisinopril and 22 atenolol ) hypertensive NIDDM patients with diabetic nephropathy were enrolled . Data from 36 patients ( 17 lisinopril and 19 atenolol , 60 ± 7 years of age , 27 men ) who completed at least 12 months of the study period are presented . At baseline , the two groups were comparable : glomerular filtration rate ( 51Cr-EDTA plasma clearance ) was 75 ± 6 and 74 ± 8 ml · min−1 · 1.73 m−2 , mean 24-h ambulatory blood pressure ( A&D TM2420 ) was 110 ± 3 and 114 ± 2 mmHg , and 24-h urinary albumin excretion rate was 961 ( range 331–5,727 ) and 1,578 ( 476–5,806 ) mg/24 h in the lisinopril and atenolol groups , respectively . The mean follow-up time was similar , 37 and 35 months in the lisinopril and atenolol groups , respectively . Mean ambulatory blood pressure was equally reduced in the two groups , 12 ± 2 and 10 ± 2 mmHg in the lisinopril and atenolol groups , respectively . Glomerular filtration rate declined in a biphasic manner with a faster initial ( 0 to 6 months ) change of 1.25 ± 0.49 and 0.81 ± 0.29 ml · min−1 · month−1 followed by a slower sustained decline ( 6 to 42 months ) of 0.59 ± 0.10 and 0.54 ± 0.13 ml · min−1 · month−1 in the lisinopril and atenolol groups , respectively . No significant differences were observed in either initial or sustained decline in glomerular filtration rate between the two groups . Urinary albumin excretion was reduced ( % reduction of baseline ) more in the lisinopril than in the atenolol group , at 55 ( 95 % CI 29–72 ) and 15 % ( −13 to 34 ) , respectively ( P = 0.01 ) . In conclusion , the relentless decline in kidney function characteristically found in hypertensive NIDDM patients with diabetic nephropathy can be reduced equally effectively by two antihypertensive treatments , the β-blocker atenolol and the ACE inhibitor lisinopril BACKGROUND The aim of this study is to compare the long-term effect of amlodipine and fosinopril in monotherapy or in combination on urinary albumin excretion ( UAE ) in hypertensive diabetic patients . METHODS We selected 453 hypertensive patients with type 2 diabetes and microalbuminuria and r and omized them to amlodipine ( 5 to 15 mg/day ) , fosinopril ( 10 to 30 mg/day ) , or amlodipine plus fosinopril ( 5/10 to 15/30 mg/day ) for a 3-month titration period . The nonresponder patients or those complaining of side effects during the titration period were discontinued ( n = 144 ) ; the remaining 309 patients were enrolled in the trial and treated with the same therapy for 4 years . Every 6 months , blood pressure ( BP ) , heart rate ( HR ) , UAE , creatinine clearance , and glycosylated hemoglobin ( HbA1c ) were evaluated . RESULTS The combination therapy was more effective in reducing BP than either drug alone at any time of the study without affecting glucose homeostasis . All three treatments provided a significant decrease in UAE during the 48-month study period . However , this effect was more pronounced and became evident earlier with fosinopril than with amlodipine monotherapy ( after 3 v 18 months of therapy ) . In addition , the combination therapy provided a greater antialbuminuric effect than the single drugs . This could be due to the greater antihypertensive effects , although other drug-specific effects can not be excluded . The cardiovascular outcomes were similar in the amlodipine and in the fosinopril group , but they were lower in the combination group . CONCLUSIONS These results strengthen the rationale to use a calcium-antagonist/angiotensin converting enzyme inhibitor combination in the treatment of hypertensive patients with type 2 diabetes |
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